Embryology and Gametogenesis PDF

Embryology and Gametogenesis Prof.Dr.Cengiz Bayçu WHAT IS EMBRYOLOGY Embryology «the unborn, embryo» is the branch of biology that studies the prenatal development of gametes (germ cells), fertilization, and development of embryos and fetuses. Additionally, embryology encompasses the study of congen...

Embryology and Gametogenesis Prof.Dr.Cengiz Bayçu WHAT IS EMBRYOLOGY Embryology «the unborn, embryo» is the branch of biology that studies the prenatal development of gametes (germ cells), fertilization, and development of embryos and fetuses. Additionally, embryology encompasses the study of congenital disorders that occur before birth, known as TERATOLOGY. 1. Embryology is the study of development of an EMBRYO FROM THE STAGE OF OVUM FERTILIZATION THROUGH TO THE FETAL STAGE Or; 2. Embryology studies the prenatal development of gametes , fertilization and development of embryos and fetuses. ICSI History Aristotle (384–322 BC) was a Greek philosopher and polymath during the Classical period in Ancient Greece. Embryologists regard him «A founder of Embryology « He was debated whether the embryo was a preformed, miniature individual (a homunculus) or an undifferentiated form that gradually became specialized. This embryo, he thought, arose from menstrual blood after activation by male.He originated the theory that an organism develops gradually from undifferentiated material, later called EPIGENESIS. The preformationism theory Preformationism (or preformism) is a formerly popular theory that organisms develop from miniature versions of themselves. Marcello Malpighi (1628 -1694) was an Italian biologist and physician, who is referred to as the "Founder of microscopical anatomy, histology & Father of physiology and embryology"also. He thought hen’s egg contained miniature chick. (preformationism theory ) Drawing of Nicolaas Hartsoeker 1656-1725 His sketch of the homunculus, a tiny preformed human he believed to exist in the head of spermatazoa, EPIGENESIS  The English physician William Harvey,((1578-1657) who labeled the theory EPIGENESIS which is accepted today and described heart and blood circulation system.  Epigenesis is the idea that organisms develop from seed or egg in a sequence of steps.  (Epigenesis, originally proposed 2,000 years earlier by Aristotle) Modern embryology developed from the work of Prussian-Estonian scientist Karl Ernst von Baer who proved epigenesis with his discovery of the mammalian ovum (egg) Karl Ernst von Baer described the oocyte in the ovarian follicle of a dog in 1827, approximately 150 years after the discovery of sperms. Karl Ernst, Ritter von Baer, 1865 Terminology in Embryology 1. Gametogenesis : Production and development of haploid male and female germ cells. The process is stimulated by 2. 3. 4. 5. 6. 7. FSH Spermatogenesis: Process of formation of sperms (testes) Oogeneis: Process of formation of ovum (ovary) Ovum: Female genus, Spermium - male genus cell Coitus: sexual intercourse Fertilization: Merging of male and female germ cells Zygote: A new structure formed by the combination of male and female cells 8. Blastocyst: Hollow structure in 1st and 2nd weeks 9. Gastrula: 3-layer (trilaminar disc) disc formation in 3-week embryo 10.Embryo : Embryo in the first 3 months 11.Fetus: Embryo after 3 months 12.Conceptus : Fetus with all additional membranes (vitellus amnion-umblical cord-chorion) Terminology In Embryology-2 1. Abortion: Birth before 20 weeks a- spontaneous b- thearepedic 2. Trimester: Clinically divided 9 months of pregnancy into 3 months 3. Organogenesis: Differentiation of organs 4. Prenatal Period: period before birth 5. Postnatal Period: period after birth 6. Newborn: First 4 weeks after birth 7. Infantile (infancy): Period from birth to the end of first year 8. Childhood: Period between 2 to 12 years 9. Puberty: Period between 12-15 years 10. Adolescence: 3- 4 th. years after puberty. 11. Adulthood: Period between 20-60 years 12. Senility: Period after 60 years and older GAMETOGENESIS Prof.Dr. Cengiz Bayçu Gametogenesis Gametogenesis (gamete formation) is the process of formation and development of specialized generative cells, gametes. This process, involving the chromosomes and cytoplasm of the gametes, prepares these sex cells for fertilization. During gametogenesis, the chromosome number is reduced by half during meiosis, (23N) a special type of cell division that occurs during gametogenesis. Gamete maturation is called spermatogenesis in males and oogenesis in females. The sperm and oocyte, the male and female gametes, are highly specialized sex cells. Each of these cells contains half the number of chromosomes(23N) (haploid number) that are present in somatic (body) cells. Male Reproductive System Front View Urinary bladder Vas deferens Seminal vesicle Urethra Prostate gland Penis Epididymis Testes Bulbourethral gland/Cowpers Gland es 1. 2. 3. 4. 5. Paired oval glands Surrounded by dense White capsule called tunica albuginea From this fibrous region, septa penetrate the organ and divide it into about 250 pyramidal compartments or testicular lobules. Each is filled with seminiferous tubules where sperm are formed Each lobule contains connective tissue with endocrine cells. Testosterone secretion by interstitial cells is triggered by the pituitary gonadotropin, luteinizing hormone (LH), which is also called interstitial cell stimulating hormone (ICSH). Testosterone synthesis thus begins at puberty, when the hypothalamus begins producing gonadotropin-releasing hormone. Seminiferous Tubules   Seminiferous tubules contain  Sperm forming cells  Sertoli cells (supporting cells) Interstitial cells in between tubules secrete testosterone (Leydig cells) Sertoli Cells Sertoli cells are columnar epithelial cells that nourish the spermatogenic cells and divide the seminiferous tubules into two (basal and adluminal) compartments. Important in Sertoli cell function are elaborate tight occluding junctions between their basolateral membranes that form a blood-testis barrier within the seminiferous epithelium. This physical barrier is one part of a system that prevents autoimmune attacks against the unique spermatogenic cells Properties of Sertoli Cells Sertoli cells support, protection, and nutrition of the developing spermatogenic cells. Because spermatocytes, spermatids and developing sperm are isolated from plasma proteins and nutrients by the blood-testis barrier. Exocrine and endocrine secretion: Sertoli cells secretory products are as follow: 1-Production of nutrients and androgen-binding protein (ABP), which concentrates testosterone to a level required for spermiogenesis, is promoted by follicle-stimulating hormone (FSH). 2- As endocrine cells, they secrete inhibin, which feeds back on the anterior pituitary gland to suppress FSH synthesis and release. 3- In the fetus Sertoli cells also secrete a glycoprotein called mullerian-inhibiting substance (MIS) that causes regression of the embryonic mullerian (paramesonephric) ducts. In the absence of MIS these ducts persist and become female reproductive track. Interstitial Tissue and Cells When the hypothalamus begins to produce gonadotropin-releasing hormone, it triggers the pituitary to produce gonadotropin, luteinizing hormone (LH) which stimulates testosterone secretion from Leydig cells. During puberty interstitial cells, or Leydig cells, develop as large round or polygonal cells with central nuclei and eosinophilic cytoplasm rich in small lipid droplets. These cells produce the steroid hormone testosterone, which promotes development of the secondary male sex characteristics. Hormonal Control Of Spermatogenesis Hypothalamus 1. 2. GnRh 3. Hypophysis Follicle Stimulating Hormone (FSH) 4. 5. Luteinizing Hormone (LH) Sertoli Cells Interstitial Cells Androgen Binding Protein+ Inhibin Testosterone Spermatogenesis 6. Hypothalamus secretes gonadotropin releasing hormone (GnRH) Anterior pituitary (hypophysis) secretes FSH and LH FSH causes Sertoli cells to secrete ABP and inhibin LH causes interstitial (Leydig) cells to secrete TESTOSTERONE ABP and testosterone stimulate spermatogenesis Control is Negative Feed Back by testosterone and inhibin Negative Feedback Control Negative feedback system occurs in the male with rising levels of testosterone acting on the hypothalamus and anterior pituitary to inhibit the release of GnRH, FSH, and LH. The Sertoli cells produce the hormone inhibin, which is released into the blood when the sperm count is too high. This inhibits the release of GnRH and FSH, which will cause spermatogenesis to slow down. Importance of Meisosis In Gametogenesis Meiosis is a special type of cell division that involves two meiotic cell divisions. It takes place in germ cells only.Diploid germ cells give rise to haploid gametes (sperms and oocytes). Meisosis; 1. Provides constancy of the chromosome number from generation to generation by reducing the chromosome number from diploid to haploid, thereby producing haploid gametes. 2. Allows random assortment of maternal and paternal chromosomes between the gametes. Relocates segments of maternal and paternal chromosomes by crossing over of chromosome The FIRST meiotic division is a reduction division because the chromosome number is reduced from diploid to haploid by pairing of homologous chromosomes in prophase and their segregation at anaphase (23 2N) IN SECOND meiotic, each of the two new cells divides again without a normal interphase (without an intervening step of DNA replication). Chromatids separate to opposite poles as individual chromosomes. In each new cell the amount of DNA per cell is reduced by half when the chromatids separate and the cells formed are haploid (23 N) It is similar to mitosis except that the cells are haploid. Spermatogenesis Spermatogenesis begins at puberty with proliferation of stem and progenitor cells called spermatogonia. Spermatogonium then undergoes mitotic division to produce two cells that become primary spermatocytes. The primary spermatocyte has 46 (44 + XY) chromosomes, the diploid number, and a DNA content of 4N. These cells enter the first meiotic prophase which produces smaller cells called secondary spermatocytes with only 23 chromosomes but DNA is 2N. Division of each secondary spermatocyte separates the chromatids of each chromosome and produces two haploid cells called spermatids each of which contains 23 chromosomes. No S phase (DNA replication) occurs between the first and second meiotic divisions therefore the amount of DNA per cell is reduced by half (1N). With fertilization, a haploid ovum and sperm produced by meiosis unite and the normal diploid chromosome number is restored. Spermiogenesis Spermiogenesis, the final phase of sperm production, is the temperature-sensitive process by which spermatids differentiate into spermatozoa, which are highly specialized to deliver male DNA to the ovum. No cell division occurs during this process, and as with spermatogenesis the cells involved remain associated with Sertoli cells. Spermiogenesis is divided into four phases: 1- In the Golgi phase the cytoplasm contains a prominent Golgi apparatus near the nucleus.. Small proacrosomal vesicles from the Golgi apparatus coalesce as a single membrane-limited acrosomal cap close to one end of the nucleus.The centrioles migrate to a position farthest from the acrosomal cap and one acts as a basal body, organizing the axoneme of the flagellum which is structurally and functionally similar to that of a cilium. 2- In the Cap phase the acrosomal cap spreads over about half of the condensing nucleus. The acrosome is a specialized type of lysosome containing hydrolytic enzymes, mainly hyaluronidase and a trypsin-like protease called acrosin. 3- In the acrosome phase the head of the developing sperm, containing the acrosome that covers a large area of nucleus and the condensing nucleus 4- In the maturation phase of spermiogenesis, unneeded cytoplasm is shed as a residual body from each spermatozoon. Sperms are mature but not yet functional or mobile. Sperm Morphology  Adapted for reaching and fertilizing the egg  Head contains DNA and the acrosome with enzymes for penetrating the egg  Midpiece contains mitochondria to form ATP for energy  Tail is flagellum used for locomotion THE FEMALE REPRODUCTIVE SYSTEM This system produces the female gametes (oocytes), provides the environment for fertilization, and holds the embryo during its complete development through the fetal stage until birth. OvervIew  Ovaries produce eggs (oocytes) & hormones  Uterine tubes transport the eggs  Uterus where embryonal and fetal development occurs  Vagina or birth canal Ovaries 1. Ovaries produce eggs (oocytes).Unlike males, who are able to produce sperm cells throughout their reproductive lives, females produce a finite (limited) number of egg cells until MENOPAUSE. OVARIES 1. Ovary covered by simple cuboidal epithelium the Germinal Epithelium and dense connective tissue Tunica Albuginea. 2. Ovary consists of the cortex, a region with a stroma of highly cellular connective tissue and many ovarian follicles varying greatly in size after menarche 3. Medulla, contains loose connective tissue and blood vessels entering the organ through the hilum Oogonia are formed in large numbers by mitosis early in fetal development from primordial germ cells. Oogenesis is the sequence of events by which oogonia are transformed into mature oocytes. This maturation process begins before birth and is completed after puberty 1. All oogonia form primary oocytes before birth, therefore a maturation of preexisting cells in the ovary. 2. In fetus, primary oocytes developed in this period stop in Prophase Stage of MEIOSIS I. 400,000 Remain At Puberty but only 400-450 Mature During A Woman’s Life Each month, hormones cause «meiosis-I» to resume in several follicles so that «meiosis II» is reached by ovulation Penetration by the sperm causes the final stages of meiosis to occur 31 Oogenesis After Puberty  After puberty primary oocyte complete meiosis I which produces secondary oocyte. This involves growth of the oocyte, proliferation and changes in the follicular cells.  The secondary oocyte begins Meiosis II, but stops in Metaphase II  The secondary oocyte is OVULATED  Meiosis II Is Completed Only If It Is Fertilized which forms ZYGOTE. 32 Ovarian and menstrual Cycle Under the control of FSH and LH secreted from the pituitary gland, monthly changes occur in the ovary and uterus throughout the woman's reproductive life until MENAPOUSE. OVARIAN CYCLE The cyclic structural changes in ovary are : Follicular phase (FSH) Development of primordial F. To Mature F. Ovulatory (Secretory) phase (LH) Release of oocyte from mature F. Luteal phase (LH) It occurs after ovulation Residual follicular cell folds and becomes part of Corpus Luteum varian Follicles Follicular Growth & Development Beginning in puberty with the release of follicle-stimulating hormone (FSH) from the pituitary, a small group of primordial follicles each month begins a process of follicular growth. This involves growth of the oocyte, proliferation and changes in the follicular cells, as well as proliferation and differentiation of the stromal fibroblasts around each follicle.  Each follicle consists of An Immature Egg Called An Oocyte  Cells Around The Oocyte Are called: Follicle cells (one cell layer thick) Stimulated to mature by FSH from the pituitary gland Granulosa cells (when more than one layer is present) Thecal cells: Cells in the ovarian stroma  Theca Interna cells Produce Estrogen 35 Primary Follicle 1° Oocyte (arrested in prophase I) Nucleus Primordial follicle Zona pellucida Thecal cells Granulosa cells 36 Secondary FollIcle Fluid-filled antrum 37 Graafian is a mature follicle in a mammalian ovary that contains a liquid-filled cavity and that ruptures during ovulation to release an egg. Corpus luteum  After ovulation, the remains of the follicle are transformed into a structure called the corpus luteum. Cells of both the granulosa and theca interna change histologically and functionally under the influence of LH, becoming specialized for production of PROGESTERONE and ESTROGENS for 10-12 days. If there is no fertilization it degenerates. Corpus Luteum In Pregnancy If pregnancy occurs, implanted embryo produce HCG hormone that maintains and promotes further growth of the corpus luteum. Stimulating secretion of progesterone to maintain the uterine mucosa for 4-5 months. (corpus luteum of pregnancy) When the placenta itself produce progesteron hormone it regresses after 4-5 months and then turns into corpus albicans. Menstrual Cycle The menstrual cycle is the regular natural change that occurs in the female reproductive system. The cycle in female is required for the production of oocytes (growth of an egg) and for the preparation of the uterus for pregnancy. Menstrual cycles are a consequence of ovarian follicle changes related to oocyte production, a woman is fertile only during the years when she is having menstrual cycles. From puberty until menopause (about age 45-50) pituitary gonadotropins produce cyclic changes in ovarian hormone levels, Estrogen & Progesteron which cause the endometrium to undergo cyclic modifications during the menstrual cycle. Phases of menstrual cycle are : Proliferation-Secretory-Menstruation Phases of EndometrIum 1. PROLIFERATIVE PHASE: With development of their thecae interna, these follicles actively secrete estrogen glands and blood vessels scattered throughout the functional zone and endometrium thickens.(8-!0 Days) 2. SECRETORY PHASE: After ovulation, the secretory or luteal phase starts as a result of the progesterone secreted by the corpus luteum. glands are enlarged and have branches. The endometrium reaches its maximum thickness (5 mm) during the secretory phase preparing the endometrium for implantation. (14 days) 3. MENSTRUATION PHASE: If there is no implantation the corpus luteum regresses and circulating levels of progesterone and estrogens begin to decrease 8-10 days after ovulation, causing the onset of menstruation or endometrium breaks down and start bleeding. (3-4days) Fertilization Fertilization is the fusion of haploid gametes, egg and sperm, to form the diploid zygote. Meiosis II is completed in this process Totipotent cells : Zygot has ability to make the whole organism. Cells that develop into every cell type of the body and can form a fully functional complete organism and these are Totipotent cells. But this ability ends on 5th day after fertilization. A Pluripotent cells : Blastocytes formed after that time and they are ONLY capable of transforming into about 200 cell types. Pluripotent are undifferentiated cells capable of being transformed in all specialized cell types that make up the organism in the embryo Zygote Zygote is a cell formed by a fertilization event between two gametes. This highly specialized, totipotent cell and its genome is a combination of the DNA in each gamete, and contains all of the genetic information necessary to form a new individual Fertilized ovum, the zygote begins as a single cell but divides rapidly in the days following fertilization and eventually becomes an embryo and then fetus. This two-week period of cell division which is the germinal period of development covers the time of conception to the implantation of the embryo in the uterus. Cell types of Blastocyte The blastocyst is a structure formed in the early development of mammals. It possesses an inner cell mass (ICM) which subsequently forms the embryo. The outer layer of the blastocyst consists of cells collectively called the trophoblast. This layer surrounds the inner cell mass and a fluidfilled cavity known as the blastocoel. The trophoblast gives rise to the placenta. First week of Development Ovulation-Fertilization-Zygote-Morula and Blastocyst Formation Fertilization is the fusion of haploid gametes, egg and sperm, to form the diploid zygote. day 3 2 1 4 5 6 ovulation Implantation About 5 days after fertilization the embryo reaches the uterine cavity, by which time blastomeres have moved to form a central cavity in the morula and the embryo enters the blastocyst stage of development. The blastomeres then arrange themselves as a peripheral layer called the trophoblast around the cavity, while a few cells just inside this layer make up the embryoblast or inner cell mass in which the embryo develops Trophoblast further differentiates and invades maternal tissues. It consist of 1. Cytotrophoblast: stem cell population 2. Syncytiotrophoblast: invasive fused cells (syncytium) derived from cytotrophoblast  At around 6-7 days implantation begins by the invasion of syncytiotrophoblasts. Diagnostic Amniocentesis 1. 2. Applied in 15th and 18th weeks of pregnancy The needle no.22 is immersed along the abdominal and uterine walls of the mother to reach the chorion and amnion and 15-20 ml of amniotic fluid is taken up and biochemical and genetic analyses. 3. Genetic disorders such as Down Syndrome, Neural Tube Defects, Congenital Metabolic disorders are revealed with this method Ultrasonography IVF (in vitro fertilization) ICSI (intracytoplasmic sperm injection) CONGENITAL ANOMALIES-MALFORMATIONS- BIRTH DEFECTS TERATOLOGY Congenital anatomic anomalies, birth defects, and congenital malformations Birth defects are the leading cause of infant mortality and may be structural, functional, metabolic, behavioral or hereditary. ANOMALIES CAUSED BY GENETIC FACTORS Numerically, genetic factors are the most important causes of congenital anomalies. It has been estimated that they cause approximately one third of all congenital anatomic anomalies Down syndrome is a genetic condition. It is not an illness or a disease. People with Down syndrome have 47 chromosomes in their cells instead of 46. They have an extra chromosome 21, which is why Down syndrome is also known as trisomy 21 People with Down syndrome associated with ; 1. physical growth delays, 2. characteristic facial features. 3. mild to moderate intellectual disability 4. Down Syndrome: β -hCG increases, Achondroplasia (Dwarfism) Achondroplasia is a bone growth disorder that causes disproportionate dwarfism. Dwarfism is defined as a condition of short stature as an adult. This is caused by mutations in the FGFR3 gene. The FGFR3 gene instructs your body to make a protein necessary for bone growth and maintenance. Hemangioma is a congenital disease and is a benign and vascular skin tumor. It is the most common type of vascular anomaly. Hemangioma is a benign (non-cancerous) abnormal growth of blood vessels Treatment : Surgical Cryotherapy Laser Trisomy 13 cleft lip and cleft palate 1. The term trisomy is used to describe the presence of three chromosome instead of two. 2. Nondisjuction of chromosomes during meisois results trisomy 3. Genetic and Environmental factors play role in this condition (Rubella virus) (cleft lip and cleft palate) Treatment : Surgery Ultrasonography Diagnostic Amniocentesis 1. 2. Applied in 15th and 18th weeks of pregnancy The needle no.22 is immersed along the abdominal and uterine walls of the mother to reach the chorion and amnion and 15-20 ml of amniotic fluid is taken up 3. Genetic disorders such as DOWN SYNDROME, NEURAL TUBE DEFECTS, CONGENİTAL METABOLİC disorders are revealed with this method Sex chromosome abnormalities An individual with an error in the number of chromosomes is defined as aneuploid. Klinefelter syndrome is a chromosomal condition is the most frequent germ chromosomal disorder IN MALES. Klinefelter syndrome occurs when X does not separate (nondisjunction) from the sexual chromosomes during cell division. Klinefelter syndrome A= 47 XXY trisomy Sterility (infertility) Gynecomastia Testicular atrophy Diabetes etc. Cause : due to the presence of an extra X chromosome (XXY) in man The shortage of testosterone can lead to delayed or incomplete puberty, breast enlargement (gynecomastia) and a reduced amount of facial and body hair. In general, patients with Klinefelter syndrome are accepted as infertile, however, assisted reproductive techniques may provide fertilization. B= 47,XYY syndrome is a sex chromosome aneuploidy in which there is an extra Y chromosome in men, Most of these men show phenotypically normal characteristics. However, an increase in the risk of infertility, cancer, neurological diseases has been reported SPINA BIFIDA Spina bifida is a neural birth defect that occurs when the spine and spinal cord don't form properly. It's a type of neural tube defect. (spinal cord remains open). The risk of neural tube defect can be determined by AFP (alphapheoprotein) measurement. TRIPLE TEST The optimal time for AFP measurement is 16 to 18 weeks 1. If the AFP is 0.5-2.5 times higher, the main disease that may occur in the baby is NEURAL TUBE DEFECT (NTD) Thank you for your attention Thank you for attention FERTILIZATION The inception of life… Lecturer, Ceren ERDEM ALTUN [email protected] 12.21.2023 FERTILIZATION ??? The process that the sperm and oocyte comes together to form a new zygote  A new organism is produced  Chromosome number is stabilized among species  Diploid chromosome number(2n) is obtained by the combination of haploid gametes (n)  Variations among species occur because of homolog recombination  Natural selection Fertilization occurs in the ampulla of the fallopian tube after a mature oocyte is ovulated from the ovary and enter the fallopian tube ~300.000.000 mil sperm is ejaculated ~200 reach the site of fertilization  The viability of the sperm is ~72 hours  The fertilization potential of the sperm is ~48 hours  The viability of the oocyte is ~12-24 hours 2) OOCYTE ACTIVATION - ZONA REACTION 1) SPERM AND OOCYTE BINDING - CAPACITATION - THE COMPLETION OF II. MEIOSIS - HYPERACTIVATION - THE EXTERNALIZATION OF THE 2. POLAR BODY - CORONA RADIATA-SPERM INTERACTION - PRONUCLEUS FORMATION - PENETRATION OF ZONA PELLUCIDA (ACROSOMAL REACTION) 3) CELL DIVISION - PENETRATION WITH OOLEMMA - DNA REPLICATION HOMOLOGUOUS CHROMOSOME PAIRING OOCYTE MEIOTIC SPINDLE ACTIVATION THE FIRST CELL DIVISION  Sperm goes through the vagina, Fallopian tubes and cells surrounding the oocyte  Mechanic, enzymatic and physiologic procedures; - Mechanically by motility - Enzymatically by the acrosomal enzymes (eg Hyaluronidase) and tubal mucosal enzymes  Sperm and oocyte interaction occurs by the help of sperm receptors on oocyte and sperm.  Sperm cells enter a maturation process called capacitation in the female genital tract after ejaculation.  These changes in the sperm enable the oocyte to penetrate the zona pellucida, that is, fertilization. MALE FEMALE  Lasts about 7 hours  Sperm do not show morphological changes in this process.  During capacitation, the glycoprotein coat and seminal plasma proteins covering the plasma membrane of sperm in the acrosomal region are removed  Only capacitated sperm undergoes acrosome reaction and fertilizes the oocyte  Capacitation is characterized by a series of biochemical and biophysical alterations to the cell; - Includes changes in intracellular pH, - remodeling of the cell surface architecture, - changes in motility patterns and initiation of complex signal transduction pathways  It occurs when sperm enters female genital tract (mucosal secretions)  After capacitation the assymmetry in flagellum motility increases, helix motility is seen  It is a pattern of motility that is required for spermatozoa to penetrate through the cumulus cell layer and the zona pellucida in order to reach the inner membrane of the oocyte Activated (A) and hyperactivated (B) spermatozoa. The numbers in the center of the sperm heads indicate successive positions of the sperm heads at 20ms intervals  The capacitated sperm comes into contact with the granulosa cells (corona radiata) around the secondary oocyte with its hyperactivation ability and passes easily between them.  Between the oocyte and the first layer of granulosa cells extracellular material accumulates called the zona pellucida  Contains three glycoproteins secreted by the oocyte  The zona pellucida is important for sperm receptors, binding specific proteins on the sperm surface and inducing acrosomal activation.  It is composed of three glycoproteins. These are produced by the growing oocyte  ZP2 and ZP3 assemble into long filaments. The sperm head first interacts with the ZP3 protein.  ZP1 cross-links the filaments into a three dimensional network Penetration of sperm with glycoproteins of the zona pellucida triggers the acrosomal reaction The head of the sperm is capped by an organelle called acrosome. The acrosome contains a trypsin-like protein (digesting enzyme) and hyaluronidase, which digests the hyaluronic acid When the head of sperm comes in contact with zona pellucida, an acrosome reaction is induced by the zona proteins.  Holes are formed in the acrosome wall of the sperm, hyaluronidase, trypsin-like substances and acrosine are released.  Hyaluronidase helps bypass the zona pellucida barrier.  Trypsin-like substances function in the digestion of zona pellucida.  Acrosine is attached to the inner acrosomal membrane. It helps the sperm to pass through the zona pellucida. The oolemma of the oocyte fuses with the sperm that has passed through the zona of the oocyte. Actin and myosin filaments in oocyte subcortical region helps the incorporation  When sperm enters the zona pellucida, a change in the properties of the zona pellucida makes it impermeable to other sperm (zona reaction).  The first answer of the oocyte to the incoming sperm is cortical reaction  The cortical granulles are released to the perivitellin space to avoid polyspermy  Fast blockage to polyspermy !!!!  It creates a barrier by the help of cortical granules (specialized secretory vesicles) located within the egg's cortex (region below the plasma membrane)  They modify an existing extracellular matrix to make it impenetrable to sperm entry  The sperm binding activity of ZP3 is lost  With the zona reaction, the binding of another sperm to ZP3 is prevented. STRUCTURES OF SPERM IN OOLEMMA : 1: oolemma 2: cell membrane of the spermatozoon 3: tail o sperm (kinocilium) 4: nucleus of the spermatozoon 5: centrosome of the spermatozoon Women are born with ~400,000 primary oocytes Oocytes experience a arrest in Meiosis I prophase at this stage. When puberty is entered, Meiosis I is completed 612 hours before ovulation, the first polar body is expelled and it is called the secondary oocyte. With the completion of Meiosis I, it continues Meiosis II and arrest at Metaphase II 2-3 hours before ovulation. If fertilization occurs, the secondary oocyte completes Meiosis II and the second polar body is expelled. 1. and 2. POLAR BODY  Nucleus materials of the gametes reorganize and form pronucleus.  The first to form is the female pronucleus, then the male pronucleus is formed.  They carry haploid genome (n) nuclei  The oocyte is called zygote from now on. Female and male pronuclei  Replication starts during the formation and growing of the pronucleuses. The main markers of the fertilization process;  2 pronuclei are formed (genetic material of the mother and father)  Excretion of 2. polar body The maternal chromosomes (22 + X) of mature oocyte condense and arrange themselves in a vesicular pattern to form the female pronucleus. Chromoses of the oocyte scatter to the cytoplasm in anaphase II. Small vesicles start to come together around the scattering chromosomes They combine to form the female pronucleus membrane. Sperm nucleus membrane dissolves Sperm chromatine dissolves in cytoplasm of oocyte (decondensation) Male pronucleus memrane is reformed and forms the male pronucleus.  The male and female pronuclei loose their cell membrane and chromosomes of two nuclei (23 in each) mix together to form diploid (i.e., 46 chromosomes) zygote. PRONUKLEUS PRONUKLEUS  The chromosomes in zygote become arranged on a cleavage spindle in preparation for cleavage of zygote.  Centriole is important for cell divisions (forming the spindle) in the zygote.  The centriole is brought by the sperm to the zygote. Dişi ve erkek prunukleuslarına ait nukleuslar METAPHASE II (MII) METAFASE I (MI) THANK YOU… 2 ndWEEK OF DEVELOPMENT IMPLANTATION Lecturer, Ceren ERDEM ALTUN [email protected] ISTANBUL OKAN UNIVERSITY 12.21.2023 Without cell growth in the embryo, division into 2 occurs mitotic divisions take place. Each mitotic division takes about 24 hours. On the 4th day, the compaction stage, that is, the borders of the blastomeres become invisible with each other and they are connected to each other. On the 5th day, the number of 200-500 cells reaches the blastocyst stage. The blastocyst falls into the uterus. This stage is called early blastocyst. (first cellular differentiation occurs at this stage) EARLY EMBRYO DEVELOPMENT PN’s fuse and dissolve in the cytoplasm (1C stage) The first cleavage starts 24 h after the fertilization, 2 cells produced The cleavage occurs by mitosis The cells are called blastomeres The cells become smaller by each division EARLY EMBRYO DEVELOPMENT Embryo have 4 blastomeres after ~48 h (2 nd day after fertilization) 8 blastomeres after ~72 h (3 rd day after fert.) Blastomeres are loosely attached to each other EARLY EMBRYO DEVELOPMENT Blastomeres starts to come together tightly attaching each other compactly in the 3-4 th day of development This stage is called the compaction EARLY EMBRYO DEVELOPMENT The cells goes on cleaving to form morula on the 4-5 th day of development They are tightly attached to each other Cell boundaries are indistinguishable After the morula stage, a cavitation begins in the early blastocyst stage and the space increases and becomes the blastocoele. blastocoele; It is filled with nutrientcontaining fluid  secreted by the endometrial layer of the uterus. During the divisions, the zona pellucida gradually becomes thinner  because the zona no longer functions It thins out and bursts from a point, the embryo starts to get rid of hatching is called blastocyst, the act of coming out is called hatched. If the embryo cannot come out of the zona, it cannot be implanted. In IVF, especially in elderly female patients and in cases where frozen embryos are thawed and transferred, zona does not burst because it hardens, at that point assisted hatching technique is applied. As fluid increases in the blastocyst cavity, it divides the blastomere into two parts: 1) Outer cell mass (ICM)= Trophoectoderm; forms the embryonic part of the placenta. The trophoblast flattens out to form the epithelial wall of the blastocyst. 2) Inner cell mass(OCM)= Embryoblast; Inner cells compact to give fetus. trophoectoderm At this stage, cells can no longer transform into another cell, their fate is determined.  called pluripotent cells. blastocoel ICM embryoblast OCM IMPLANTATION IMPLANTATION: The attachment of the embryo in the blastocyst stage to the uterine wall (endometrium) is called. Location: posterior wall of the endometrium, close to the fundus. time: 6-7 days after fertilization. implantation takes about 1 week. The first week of embryo development takes place in the fallopian tubes, and the second week in the uterus in the endometrium. UTERUS  Uterine wall consits of three layers: 1) Endometrium: the inner layer of the uterus - Functionalis (functional layer) - Basalis (basal layer) 2) Myometrium: a thick muscle layer 3) Perimetrium: the outer periton membrane Endometrium shows periodic differences in every menstruel cycle (28 days) by hormonal control Uterine receptivity finishes on 20-24 th day of the menstrual cycle UTERUS  During menstruel cycle uterus have 3 stages: 1) Follicular/ proliferative phase: follicular development 2) Secretory/ progestational phase: starts 2-3 days after ovulation. Endometrium is reestablished 3) Menstruel phase: if implantation don’t occur, the layers become degenerated and menses (bleeding) occurs  Implantation occurs in the secretory phase UTERUS In the follicular stage, the surface of the endometrium begins to thicken. Endometrium >11 mm ideal, In IVF, the endometrium is thickened by giving progesterone and estrogen externally. ENDOMETRIAL RECEPTIVITY  The endometrium is ready to accept the embryo. - Includes; morphological(artery lengthens, endometrium thickens) Genetic metabolic actions.  Surface receptors undergo superficial modification to accept the embryo.  Factors affecting implantation : - quality of the embryo - Endometrial receptivity - maternal age - Timing - hormonal status - metabolic and genetic status IMPLANTATION WINDOW Defines a time and a place. there is a short period of time during which the implantation window is open  a certain area of the endometrium is ready to receive the embryo for a short time. This event takes place 6-10 days after ovulation. Endometrial receptivity and implantation window are affected by; - cytokines (IL-1β and IL-1α), - β-HCG - signaling mechanisms produced by the blastocys STAGES OF IMPLANTATION The process of implantation may be separated into a series of developmental phases starting with the blastocyst hatching and attachment to the endometrium  These steps: - Apposition: first contact - Adhesion: adhesion (here may not like and implant the embryo  natural selection) - Penetration: start to sink in - Invasion: full embedded STAGES OF IMPLANTATION STAGES OF IMPLANTATION After the first attachment, signaling pathways are triggered and the entire endometrium undergoes changes. This is called a decidual reaction. After this point, the endometrium transforms into decidua cells. Decidua cells begin to synthesize and store lipid and glycogen (they will feed the embryo), decidua cells are larger, lighter colored and rich in glycogen than fibroblasts. At the penetration stage, the embryo will release enzymes that break down proteins and push itself deeper. STAGES OF IMPLANTATION It is well embedded in invasion and seals itself with a clot (fibrin plug). Nothing is visible on the uterine surface anymore. DURING IMPLANTATION; 1) Cytotrophoblast: 2) syncytiotrophoblast  The protrusions of trophoblast cells that adhere into the endometrium differentiate to become a new type of cells, syncytiotrophoblast.  The rest of the trophoblasts surrounding the inner cell mass will be referred to hereinafter as cytotrophoblasts.  As this process takes place, changes ocur in ICM, producing a bilaminar embryonic disc composed of two layers, the epiblast and hypoblast  At the end of the first week, a layer of cells, called the hypoblast, first appears on the surface of the embryoblast, facing the blastocyst cavity  The embryonic disc gives rise to germ layers that form all the tissues and organs of the embryo. 1: desidua cells 2: hypoblast 3: syncytiotrophoblast 4: Cytotrophoblast 5: Epiblast Multiple pregnancy is the development of more than one fetus in the uterus during the same gestational period. Multiple pregnancy usually occurs when more than one oocyte is ovulated and fertilized in the same cycle. Rarely, a single zygote splits into two in the early stages of division, forming egg different embryos. Since these embryos carry the same genetic material, they are very similar to each other. These embryos often share the same placenta monozigotic dyzigotic Their genetic material is not the same, and they are as similar to each other as siblings born at different times. TEŞEKKÜR EDERİM… Lecturer CEREN ERDEM ALTUN [email protected] ISTANBUL OKAN UNIVERSITY 08.02.2024 2ND WEEK: IMPLANTATION + BILAMINAR GERM DISC Bilaminar germ disc 3RD WEEK: GASTRULATION + NOTOCORD FORMATION ❑ Transformation of bilaminar germ disc into trilaminar germ disc. ❑ It is the beginning of morphogenesis (formation of body shape). ❑ It is characterized by the formation of three germ sheets (ectoderm, mesoderm and endoderm) in the embryo. Each of these three germ sheets forms special tissues and organs. ❑ At this stage, the embryo is also called the gastrula. 3RD WEEK: GASTRULATION + NOTOCORD FORMATION The first sign of gastrulation is the appearance of the "primitive streak" in the caudal part of the embryo. The primitive streak, which is not very prominent at first, appears as more raised regions running along either side of a shallow groove in the 15-16 day embryo. While the primitive streak extends in this direction with the addition of cells to its caudal end, the primitive node (nodus primitivus) is formed by cell proliferation at the cranial (cephalic) end. Meanwhile, a narrow groove, called the primitive groove, develops in the primitive streak. The primitive groove continues with a depression formed in the primitive node, and this depression is called the primitive pit (fovea primitiva). Epiblast cells migrate towards the primitive streak. When they reach the primitive streak, the balloon-shaped cells separate from the epiblast and slide under the epiblast along the primitive groove. This inward movement of cells is called invagination. The epiblast is the source of the three germ sheets (ectoderm, mesoderm, endoderm) from which all the tissues and organs of the embryo will develop. When the primitive streak appears, it is possible to identify the cranial and caudal aspects of the embryo, its dorsal and ventral aspect, its right and left sides. Some of the cells invaginated from the primitive streak enter between the hypoblast cells and enter the embryonic (intraembryonic) endoderm at the ceiling of the yolk sac, Some spread between the epiblast and the newly formed endoderm to form the intraembryonic mesoderm, Cells remaining in the epiblast form the embryonic (intraembryonic) ectoderm. Primitive streak These cells have the potential to proliferate and differentiate into various cell types such as fibroblasts, chondroblasts and osteoblasts. ECTODERM Epidermis including hair, nails sebaceous glands mammary glands Central and Peripheral Nervous System Ear, nose, eye sensory epithelium Pituitary gland tooth enamel ENDODERM Epithelial lining of the gastrointestinal and respiratory tracts Epithelial lining of the tympanic antrum pharyngotympanic or auditory tube Epithelial lining of the bladder and most of the urethra Liver, Pancreas parathyroid gland Thymus Thyroid tonsils MESODERM Smooth muscle layers, Skeletal and Skeletal muscles Connective Tissue, Cartilage and Bone Veins associated with tissues and organs Most of the cardiovascular system Blood cells and Bone Marrow Reproductive and Excretory Organs (kidney, gonad and related ducts) NOTOCORD FORMATION Prenotochordal cells invaginating from the primitive pit migrate in the cephalic direction up to the prechordal plate, and by mixing these cells into the hypoblast, they form a cellular cord called the notochordal plate (notochord extension) for a short time in the midline of the embryo. A lumen is formed within the notochordal plate (notochord extension) in a short time and is called the notochord canal. Primitive streak Primitive streak There are occasional lysis in the notochord canal floor and the underlying endoderm. These melting areas coalesce and the base disappears completely for a while A plate that bends inward from the ceiling ends that remain intact forms the NOTOKORD PLATE. The hypoblast leaves its place to endoderm cells moving inward along the primitive streak, and the cells of the notochordal plate proliferate and break off from the endoderm Starting from the cranial, the plaque curves more and forms the permanent (definitive) NOTOCORD, which is a solid cord of cells. END OF THE 3RD WEEK; It determines the primordial axis of the embryo and gives the embryo perpendicularity. It forms the basic signals for the development of the axial skeleton (cranial bones and spine). It determines the place where the vertebral bodies will form in the future. It stimulates the embryonic ectoderm and induces the formation of the neural plate. FATE OF THE PRIMITIVE STREAK; In normal conditions, the primitive streak undergoes a degenerative change and disappears at the end of the 4th week. The persistence of primitive streak remnants can result in a large tumor called a sacrococcygeal teratoma. Sakrokoksigeal Teratom 4TH WEEK= NORULATION= NEURAL PLATE AND NEURAL TUBE FORMATION When the notochord develops, it induces the overlying ectoderm. With the thickening of the ectoderm, a structure called the neural plate occurs. At the beginning of the 3rd week, the neural plate is in the form of a flat disc that is wide in the cephalic region and narrower in the caudally. The cells of the plate form the neuroectoderm, and the induction of these cells represents the beginning of the neurulation process. As the notochord lengthens, the neural plate expands and moves cranially. At approximately 18-19 days, the neural plate invaginates along its central axis, forming the neural groove that runs longitudinally in the midline with neural folds on either side. As a result of the contraction of ACTIN and MYOSIN fibers, which work like a muscle in the cells forming the neural plate, the middle of the neural plate becomes dimpled and the neural groove is formed. While the folding continues, the neural groove edges come together, the opposite cells are adhered by cell adhesives called FIBRONECTIN to form the NEURAL TUBE (primordium of the CNS). FORMATION OF SOMITS When the notochord and neural tube are formed, the intraembryonic mesoderm on both sides of them proliferate to form the paraxial mesoderm columns. Each column continues laterally with the intermediate mesoderm, and the intermediate mesoderm continues with the gradually thinning lateral mesoderm layer. Towards the end of the third week, the paraxial mesoderm differentiates and begins to divide into pairs of cubic bodies called somites. These mesoderm blocks are located on either side of the developing neural tube. During the somite development period (days 20-30), approximately 38 pairs of somites are formed. At the end of the 5th week, there are 42-44 pairs of somites. Since they are very prominent at the 4th and 5th weeks, they are among the criteria used to determine the age of the embryo. They form the dermis of the adjacent skin, with most of the axial skeleton (skull bones, spine, ribs, and sternum) and associated muscles. The neural tube develops on both sides of the somites Wide openings cranial and caudal => NEUROPORE EMBRYO FOLDS The amniotic cavity completely surrounds the embryo in all directions and becomes the dominant cavity. It grows gradually. The yolk sac narrows on all sides and becomes a small sac connected to the midgut by a narrow vitelline duct. It gets smaller. The extra-embryonic coeloma is gradually destroyed by the enlarging amnion and eventually disappears completely. On the 24th day, the first 2 pharyngeal arches are seen. 1. Pharyngeal arch (mandibular) is more prominent. 1. Pharyngeal arch; - for the most part → the mandible (lower jaw) is formed, - from the rostral projection → maxillary protrusion (upper jaw) occurs The embryo is slightly curved due to head and tail folds. The heart is selected as a large protuberance ventrally and pumps blood.. On day 26, 3 pairs of pharyngeal arches are observed in the embryo. The anterior neuropore of the neural tube is closed The forebrain protrudes considerably in the head region, and the curling of the embryo gives it the typical C shape. Upper limb buds 26-27. occurs per day. It appears as a small bulge on the ventrolateral wall of the body. Otic pits with outlines of the inner ear are seen. Ectodermal thickenings called the lens plate, which will form the lens of the eye, are seen on both sides of the head. At the end of the 4th week, 4 pairs of pharyngeal arches and lower extremity buds are evident. The long tail-like caudal protrusion is characteristic at the end of the 4th week. Many organ systems, especially the cardiovascular system, have begun to form. By the end of the 4th week, the posterior neuropore of the neural tube is usually closed.. WEEK 5 OF DEVELOPMENT Less changes are observed compared to the changes in the 4th week. Head growth is higher than other regions. The main cause of head growth is the rapid development of the brain and facial outlines. 2. Pharyngeal arch develops more than the others, covers the 3rd and 4th pharyngeal arches and forms lateral pits on both sides → CERVICAL SINUS The mesonephric ridges on either side are the mesonephric kidneys, which will form the temporary excretory organs in humans. WEEK 6 OF DEVELOPMENT The embryo reflexively responds to touch at 6 weeks. With the formation of hand plates on the upper extremities, a regional differentiation begins. FINGER SHARPS appear on the hand plates, which will enable the fingers to be shaped. Spontaneous twitches are seen in the lower and upper extremities. Lower extremity development occurs 4-5 days before upper extremity development. AURICULA CAPES develop around the 1st and 2nd pharyngeal arches, from which the external auditory canal is formed. The eye becomes prominent with the intense pigment formation in the retina. Due to the bending in the neck region, the head is bent in front of the heart protrusion. The intestines enter the embryonic coeloma proximal to the umbilical cord. WEEK 7 OF DEVELOPMENT Significant changes are seen. Clefts form between finger outlines and fingers can be distinguished The connection between the primitive gut and the umbilical sac (the vitellus sac) decreases and turns into the omphaloenteric duct. At the end of the 7th week, ossification begins in the upper extremities. WEEK 7 OF DEVELOPMENT = LAST WEEK OF THE EMBRIONIC PERIOD At the beginning of the this week, the fingers of the hand are separated, but they are webbed. There are prominent slits between the toes. The scalp vascular plexus is observed and forms a characteristic band around the head. At the end of the 8th week, all contours of the extremities are evident, the fingers are extended and completely separated from each other. WEEK 8 OF DEVELOPMENT; Voluntary movement of extremities seen for the first time Ossification begins in the femur At the end of the 8th week, the caudal process (tail) disappears completely. Hands and feet converge ventrally At the end of the 8th week, the embryo has human appearance. The eyes are well developed and the eyelids are closed to protect the eye from muscle movements of the fingers. AT THE END OF WEEK 8 At the end of the 2nd month, that is, at the end of the embryonic period, the embryo is 21-31 mm in length and weighs 9.5 g After the 8th week, the fetal period begins and the person in this developmental period is called a residual fetus. 06.02.2023 FETAL DEVELOPMENT Lecturer, CEREN ERDEM ALTUN 15.02.2024 ISTANBUL OKAN UNIVERSITY, DEPARTMENT OF HISTOLOGY&EMBRYOLOGY FETAL PERIOD: The period from the 9th week until birth In this period; - body grows quickly → body development is very fast - tissues, organs and systems differentiate - Fetal weight gain accelerates in the last weeks GROWTH AND AGE CALCULATION Height and age of the fetus during the fetal period; - Crown rump length (CRL) - crown-to-heel (CHL) are measured by values. AC: amniotic cavity CC: chorionic cavity PREGNANCY TRIMESTERS Clinically, the pregnancy period is divided into 3 trimesters of 3 months each. all major organ systems are developed the size of the fetus develops sufficiently so that anatomical details can be seen during ultrasonography → fetal anomalies can be detected If the fetus is born prematurely (immature) at the beginning of the 3rd trimester, it may survive. The greatest development in the fetus occurs in the 35th week, - weight is ~2500g → It is a measure of fetal maturation. GROWTH AND AGE CALCULATION Crown rump length measurement (CRL) is the preferred method for fetal age determination until the end of the 1st trimester. - because very small changes occur in the fetal body during this period. FETUS DEVELOPMENT BY WEEKS While the growth of the fetus in length is more evident in the 3rd - 5th months, the increase in its weight is more evident in the last 2 months. SHAPING OF THE FETUS ❖ By the end of the 1st trimester, the fetus's face becomes more humanlike. ❖ The limbs also lengthen; but the legs are shorter and less developed than the arms. ❖ Eyes begin to develop on the side of the face and move forward. ❖ Ears take their final place. SOME IMPORTANT PROCESSES taste buds : 7th week swallowing : 10th week respiratory movements : 14th-16th weeks sucking movements : week 24 Hearing : 24th-26th week Vision (sensitivity to light): 28th week BETWEEN WEEKS 9 AND 12 ✓ At the beginning of the 9th week; The head is half the length of the CRL of the fetus. ✓ Thereafter, trunk length growth increases rapidly and by the end of the 12th week, it is more than twice the CRL. Week 11 Week 9 BETWEEN WEEKS 9 AND 12 9th week 12th week The face is wide, the eyes are wide apart, the Primary ossification centers of the skeleton, ears are lower than normal, and the eyelids especially the skull and long bones, appear. are not opened. The legs are short and relatively small. The upper extremities gain their relative final length, but the lower extremities are shorter than their final size Male and female external genitalia look similar Does not reach mature fetal shapes until the end of the 12th week The liver undertakes most of the hematopoiesis At the end of the 12th week, the spleen takes over the function of the fetal liver. Urine production begins between the 9th and 12th weeks. The fetus excretes urine into the amniotic fluid, which reabsorbs some of it after drinking it. Fetal waste materials are transferred across the placental membranes into the maternal bloodstream. BETWEEN WEEKS 13 AND 16 Development is very rapid during this period.. At the 16th week, the fetal head is relatively small compared to the 12th week, and the lower extremities are elongated. Leg movements first begin at the end of the embryonic period→ It becomes coordinated in the 14th week, but is felt very weak by the mother. → These movements are seen during ultrasound. Fetal skeletal ossification is active → At the beginning of the 16th week, bones are easily observed on ultrasound. BETWEEN WEEKS 13 AND 16 Slow eye movements are observed in the 14th week. In the 16th week, the ovary, consisting of primordial follicles containing oogoniums, differentiates. External genital organs recognizable At the 16th week, the external appearance of the fetus becomes more human-like (ears and eyes settle in their normal places). Week 13 BETWEEN WEEKS 17 AND 20 Development slows but the fetus is still growing and the CRL is approximately 50 mm. Accelerated fetal movements are felt by the mother. BETWEEN WEEKS 17 AND 20 The skin is covered with a fatty cheese-like substance called VERNIX CASEOSA. It consists of a mixture of fat secreted from the sebaceous glands and dead epithelial cells. It protects the fetal skin from abrasion, cracking and damage that can be caused by amniotic fluid. BETWEEN WEEKS 17 AND 20 Eyebrows and hair appear in the 20th week → The whole body is covered with thin hairs called LANUGO. - These hairs help the vernix caseosa to adhere to the skin. Brown fat forms during this period. - It is the energy store of the newborn. - This special fat tissue produces energy by oxidation of fatty acids. - brown adipose tissue mainly; It is located at the base of the neck, behind the sternum and around the kidney. In the 18th week, the uterus forms in the female fetus and the vagina begins to drain. Many primordial follicles are formed in the ovary. In the male fetus, at the 20th week, the testicles begin to descend towards the scrotum from hanging on the posterior abdominal wall. BETWEEN WEEKS 21 AND 25 There is a significant weight gain in the fetus and the head-to-body ratio becomes more realistic Fetal skin is more wrinkled and transparent. - In fresh specimens, the skin color ranges from pink to red. → Blood may be observed within the capillaries. Rapid eye movements begin at week 21. - It has been reported that the fetus responds to vibroacoustic sounds originating from the womb by blinking in the 22nd and 23rd weeks. Nails form in the 24th week. BETWEEN WEEKS 21 AND 25 Type II pneumocyte cells (secretory epithelial cells) in the alveolar wall of the lung begin to secrete surfactant, which ensures the effectiveness of the developing alveoli. 22.-25. When a week-old fetus is born prematurely, it can survive if it is taken to intensive care.However, it can also result in death because the fetus's respiratory system is not yet mature. Babies born before the 26th week of gestation have a high risk of neuronal developmental delay. BETWEEN WEEKS 26 AND 29 The fetus's lungs have the ability to breathe during this period → If birth occurs, it can survive with care. - lung and pulmonary vessels are sufficiently developed for gas exchange. The central nervous system is mature enough to regulate rhythmic respiratory movements and body temperature. Most deaths in newborns occur due to low (≤ 2500 g) and very low (≤ 1500 g) birth weight. BETWEEN WEEKS 26 AND 29 Eyes open at 26 weeks. Hair and lanugo are well developed. Some amount of subcutaneous fat tissue has formed, which corrects skin wrinkles. During this period, the amount of white fat reaches approximately 3.5% of body weight. Towards the end of the 28th week, the spleen's role in hematopoiesis ends → bone marrow takes over. BETWEEN WEEKS 30 AND 34 The pupillary light reflex in the eye (the change in diameter of the pupil as a response to light) can be determined at the 30th week. At the end of this period, the skin is generally pink and smooth. The amount of white fat is approximately 8% of body weight. Fetuses 32 weeks and older generally survive as a result of premature birth. BETWEEN WEEKS 35 AND 38 A normal fetus at birth weighs 3000-4000 g, CRL is 36 cm, CHL is 50 cm. The gender characteristics of the fetus are evident and the testicles have descended into the scrotum. In the last two months, subcutaneous fat tissue begins to accumulate, thus body lines become rounder. EXPECTED DATE OF BIRTH ❑266 days or 38 weeks after fertilization. ❑In other words, it is 280 days or 40 weeks after the 1st day of the last menstrual cycle. ❑However, 12% of babies are born 1 or 2 weeks after the expected due date. Immature baby: Those born before the 27th week Premature baby : Those born between 29-32 weeks Borderline premature Those born at 33-36 weeks Mature : Those born between 38-42 weeks Postmature : Those born after the 42nd week FACTORS AFFECTING FETAL GROWTH ❖Maternal, fetal and environmental factors can affect prenatal growth. ❖Factors that continue throughout pregnancy, such as maternal vascular disease, intrauterine infection, smoking, alcohol consumption → It leads to babies with intrauterine growth restriction (IUGR) or small for gestational age (SGA) babies. ❖Factors acting during the last trimester, such as maternal malnutrition, often result in babies with low birth weight despite having normal length and head growth. ❖Babies whose birth weight is 10% or less compared to gestational age are called low birth weight babies (SGA-IUGR). FACTORS AFFECTING FETAL GROWTH ❖IUGR; It refers to a process that causes a decrease in fetal growth and potential as expected. ❖SGA; It refers to a baby whose birth weight is lower than the predetermined value for a certain gestational age. The most important factor that ensures prenatal development is insulin-like growth factor 1 (IGF 1). IGF 1 is secreted by fetal tissues. Growth after the baby is born is regulated by growth hormone (GH). After GH binds to the receptor, it initiates IGF1 secretion. Laron dwarfism is observed as a result of mutations in the GH receptor. There is no IUGR in these babies. ASSESSMENT METHODS OF FETAL CONDITION It is possible to follow the development and growth of the fetus in the uterus with some methods. One of these is ultrasonography. → With this method, malformations such as the position of the placenta and fetus, multiple pregnancies, neural tube, heart and anterior abdominal wall defects can be detected. ASSESSMENT METHODS OF FETAL CONDITION Another technique used is amniocentesis. → The best time for amniocentesis is 16-18 weeks of pregnancy, counting from the last menstrual date. → In this technique, which allows the removal of some amniotic fluid, a special needle is entered into the amniotic cavity through the mother's abdominal and uterine walls and 20-30 ml of amniotic fluid is withdrawn. ASSESSMENT METHODS OF FETAL CONDITION Amniotic fluid is looked for α-fetoprotein (AFP), a fetal protein. This protein increases in neural tube defects such as anencephaly and anterior abdominal wall malformations such as omphalocele. Apart from this, fetal cells in the amniotic fluid can be grown in cell culture and analyzed for chromosomal abnormalities. ASSESSMENT METHODS OF FETAL CONDITION Another technique is chorionic villus biopsy. → By examining this tissue, which contains rapidly dividing fetal cells, biochemical defects such as chromosomal and congenital metabolic diseases can be detected in a short time. → All these techniques, except ultrasound, are used only in high-risk pregnancies. ASSESSMENT METHODS OF FETAL CONDITION These tests; → older maternal age (35 and over) → Previous family history of neural tube defects → There is another child in the family with abnormalities such as Down syndrome → Having a chromosomal anomaly in one of the parents → the mother is a carrier for one of the X-linked recessive diseases it is done in such cases. PLACENTA and FETAL MEMBRANES Prof.Dr.Cengiz Bayçu -2024 Objectives Describes the structure and function of the placenta, umbilical cord , amnion ,yolk sac,allantois: The extaembryonic of fetal membranes They originate from the embryo, but are not considered part of it. They typically perform roles in nutrition, gas exchange, and waste removal Fetal Membranes and Placenta: Their origin is ZYGOT Membranes : 1. Yolk (Vitelline) sac 2. Amnion 3. Allantois 4. Chorion The fetal membranes are four of six accessory organs developed by the conceptus that are not part of the embryo itself, the other two are the placenta, and the umbilical cord. 1. Umbilical cord 2. Placenta Development of Yolk sac and Amnion (8 through 14 days of 3 week embryogenesis) The inner cell mass becomes a bilaminar disc as it divides into the: A- HYPOBLAST, which forms the YOLK SAC, B- EPIBLAST, which forms the AMNION. The yolk sac and amnion develop simultaneously, which begins during eight (8) day through day-14 of embryogenesis. inner cells Yolk Sac (vitellin sac) Yolk sac forms from proliferating HYPOBLAST cells after implantation. It attaches ventrally to the developing embryo via the yolk stalk. The yolk stalk connects the yolk sac to the midgut, which is an early derivative of the gastrointestinal system. Both the midgut and yolk sac are endodermal in origin. The yolk sac has several critical biological functions during early gestation such as ; 1. It is the structure that provides NUTRITION in the second and third weeks. 2. It is site of «PRIMITIVE HEMATOPOIESIS AND FIRST BLOOD» production at 3rd.week 3. It is site of «GERM CELL« production. Primordial germ cells that appear in the endodermal epithelium of the sac (3rd week) they migrate towards the gonads 5-6 week In 4 th. week, it appears as a MIDDLE INTESTINE, and from here the epithelium of the trachea,lungs and digestive tract develops in the future. The sac is quite large in first month but regresses every week and at 20 week , it becomes very small and then disappears Amniotic Fluid It begins to form from the 12th day of fertilization. The amonut of the fluid is ; 30 ml at the 10th gestational week, 50 ml at the 12th gestational week, and 800 to 1000 ml at full term (40 weeks) Contents ; 99% water ,exfoliated epithelium, carbonhydrate, Protein,Fat, Enzyme,Hormone, 400cc of liquid is swallowed by the fetus per day. A. B. The liquid passes into the respiratory and digestive system and into the fetal bloodstream.Waste products are transferred to the maternal circulation through the placenta. Urine and other substances (water) excreted by the fetal kidneys pass into the amniotic fluid and are swallowed again by the fetus. C. Meconium (fetal feces) formation in the fetus is observed in the last stages of pregnancy Circulation of Amniotic fluid 1. The water content of the amniotic fluid changes every 3 hours. 2. A large amount of water enters the mother's tissue through the chorioamniotic membrane and enters into the uterine capillaries. 3. The exchange of fluid with fetal blood occurs through the umbilical cord, which is connected to the chorionic plate of the amnion on the fetal side of the placenta Fetal face Maternal face Functions of Amnion 1. Plays role in Symmetrical growth of the embryo 2. Protects the embryo/fetus against infections 3. Protects fetus from mechanical impacts 4. Ensures normal lung development of the fetus 5. Maintains optimal retention of body temperature 6. Ensures the free movement of the fetus and the normal development of the muscular system 7. Maintaines homeostasis and electrolyte balance 8. It is a Immunological barrier AMNIOTIC FLUID PROBLEMS Oligohydramnios: (500 ml) Fluid deficiency due to renal agenesis or lack of placental circulation. Low amniotic fluid volumes can be the result of numerous maternal, fetal, or placental complications and can lead to poor fetal outcomes. (Fetal and Placenta deffiency, maternal hypertension) Polyhydramnios (2000 ml.) Increased amount of fluid due to inability to swallow fluid 1. CNS disorder or Esophageal atresia of the foetus 2. Blockages in the baby's intestine 3. Pathologies that prevent swallowing in the baby (fetal goiter, masses on the neck 4. Having diabetes in the mother Various drug and substance uses (cocaine, heroin use or lithium treatment) Meconium Aspiration (MAS) and Birth Injury Under normal circumstances, a fetus’s meconium (excretory matter,feces) is stored in the intestines until after delivery. However, distress of the baby like infection or lack of oxygen can cause passage of meconium into the amniotic fluid before or during birth. Which can cause fetus to inhale the meconium and The mixture can then travel to their lungs and the baby may breathe (aspirate) it into lungs just before, during, or after birth. This amniotic fluid. is known as meconium aspiration syndrome (MAS). The most common signs of fetal distress are: 1. 2. 3. 4. 5. Difficulty in breathing due to precense of meconium in the lungs. Changes in the fetal heart rate (lower or higher rate than normal). The fetus moves less for an extended period of time. Low amniotic fluid. Oxygen deficiency Main Causes : 1. 2. 3. Compression of the head and/or umbilical cord due to hypoxia or hypoxia, Increased vagal stimulation due to hypoxia Relaxation of the anal sphincter due to increased intestinal peristalsis cause meconium to flow into the amniotic fluid. Treating methods of MAS 1. 2. 3. 4. 5. 6. 7. 8. Endotracheal intubation and mechanical ventilation as needed. Supplemental oxygen as needed to keep PaO2 high to relax pulmonary vasculature. Surfactant or antibiotics to open lungs and clear any infection. IV antibiotics. Inhaled nitric oxide in severe cases of PPH. The meconium aspiration of the fetus cannot be prevented. However , To prevent severe aspiration is may possible by ; To monitor the amniotic fluid for meconium and watch for fetal distress Detecting aspiration early and quickly Allantois About at 3rd week it begins to appear in the form of a caudal protrusion from the YOLK SAC AND Moves Inside The Connectıng Stalk Of The Embryo Function of Allantois In the embryonic period ; 1- Plays role in RESPIRATION by exchanging gases with the chorionic membrane 2- Participates in the development BLADDER and it is site of urine storage in this period 3- Participates in the DEVELOPMENT OF BLOOD and UMBILICAL CORD VESSELS. After the second month, it regresses and than the PLACENTA AND AMNION BEGIN TO FUNCTION UMBILICAL CORD A. The umbilical cord is the vital connection between the fetus and the placenta. Connects the embryo/fetus to the maternal placenta. In the womb, the umbilical cord provides the OXYGEN AND NUTRIENTS needed for the embryo to grow. B. It is formed by the (5) fifth week of development and it functions throughout pregnancy to protect the vessels that travel between the fetus and the placenta. At 8-10 week , the umbilical formed. cord has fully By the 10th week the gastrointestinal tract has developed and protrudes through the umbilical ring to form a physiologically normal herniation into the umbilical cord Blood Vessels of the umbilical cord: A- With the Umbilical vein carrying oxygenated blood with nutrients from the placenta to the fetus (Chorioamniotic membrane) B- Umbilical arteries transporting deoxygenated blood with waste products from the fetus to the placenta. Wharton jelly consist of 2 arteries 1 vein -mucous connective tissue Arteries Vein Umbilical cord entanglement and knot Hypoxia- Brain damage and mental retardation in the fetus in case of oxygen deficiency for more than 5 minutes. Anoxia (oxygen deficiency) and death are observed in the knotting The Placenta 1. The placenta begins to develope from the blastocyst shortly after implantation. 2. The placenta and umbilical cord are transport organs 3. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate maternal and fetal circulations 4. It is an important endocrine organ producing hormones that regulate both maternal and fetal physiology during pregnancy. Functions Protection Nutrition Respiration Excretion Production of hormone Development of Placenta Developes From DECIDUA BASALIS and CHORION FRONDOSUM In 3rd week the anatomical and physiological connection is established between the embryo and the mother 1- TROPHOBLAST are cells forming the outer layer of a blastocyst, which provides nutrients to the embryo, and develops into a large part of the placenta. They are formed during the first stage of pregnancy and are the first cells to differentiate from the fertilized egg. 2- In second week the differentiates during implantation into the following: 1- The CYTOTROPHOBLAST, a layer of mitotically active cells around the amnion and yolk sac. 2- The SYNCYTIOTROPHOBLAST, a more superficial, nonmitotic mass of multinucleated cytoplasm which invades the surrounding stroma. As a result, from these layers CHORION is formed (FETAL PLACENTA) The formation of vascularization on week 4 and accordingly, the start of nutrition and gas exchange between embryo and mother. Parts of Placenta A- Fetal Placenta : CHORION: The chorionic membrane is a fibrous tissue layer containing the fetal blood vessels. The chorionic villi are involved in fetal-maternal exchange which is two parts ; 1. Chorion Laeve (smooth) : the smooth part of the chorion that lacks villi and is not part of the placenta. 2. Chorion Frondosum The part of the chorion that has persistent villi and that with the decidua basalis forms the placenta B- Maternal Plasenta : Desidua basalis (in Uterus endometrium) Human Placenta 1. 2. Placenta also called ; Placenta cotylodonata Placenta discoidalis 3. Placenta hemochorialis Placental barrier: Chorion Villi consist of : a. Cytotrophoblast-syncytiotrophoblast layers b. Connective tissue of villi c. Vascular endothelium of villi 1 Placenta Layers 2 1. Decidua parietalis: the part that covers the inside of the uterus 2. Decidua basalis : the layer that forms the maternal placenta 3. Decidua capsullaris : the part of the placenta that surrounds the fetus 3 DECIDUA : Endometrium gravidarum The decidua forms the maternal part of the placenta and remains for the duration of the pregnancy Composition of Decidua A- Cells Macrophages, Lymphocytes, Granulocytes, Decidual cells B-Exstracellular matrix Laminin ,Fibronectin Kollagen type-IV Heparan sulfate, proteoglycan 1- Decidual cells are stromal cells in the uterine endometrium that develop, grow and accumulate glycogen-fat due to an increase in Progesterone during pregnancy 2- Decidual cells also protect the mother from the attack of syncytiotrophblasts Placenta after birth Maternal Fetal Vascularization of the Chorion Villi 10 week Mature a.CytotrophoblastSyncytiotrophoblast layers b.Connective tissue of villi c.Vascular endothelium of villi Histology of Mature Placenta--1 Functions of Hofbauer cell: 1-Macrophage-like cells and are involved in defense 2- Ensures the formation of the villi stroma 3-Controls the flow of placental fluid 4-Control of vasculogenesis 5-Possibly indirectly stimulate collagen production Fetal-placental circulation 1. Oxygen-poor blood leaves the fetus and enters the placenta through the Umbilical Arteries 2. 3. 4. These vessels in the placenta are divided into many branches and form a dense ARTERIO-VENOUS CAPILLARY SYSTEM IN THE VILLI This system forms a very large surface that performs metabolism and gas exchange between the mother and the fetus The oxygenated blood in the fetal capillaries passes through the veins, these veins merge to form the Umbilical Vein, which carries oxygen-rich blood to the fetus. Placenta as Allograft and Tissue Rejection 1. Allograft : An allograft is tissue that is transplanted from one person to another 0r a tissue graft taken from another individual (donor) who is the same species as the recipient 2. The placenta is an allograft according to the mother. The concept is the part that forms the Fetal Part of the Placenta that carries the genetic material of the mother and father. In this case, how is the placenta protected from the immune system of the mother or why the mother does not reject the placenta ? 3. 4. The fetal-maternal immune system determines the fate of pregnancy. THE TROPHOBLAST cells not only give an active response against external stimuli but are also involved in secreting most of the cytokines. These cells have an essential function IN FETAL ACCEPTANCE OR FETAL REJECTION. Tolerance of the fetus by the maternal immune system: role of inflammatory mediators at the fetalmaternal interface and Factors that play role in tissue rejection DECIDUA provide an immuno protective environment for the development of the embryo. A. Cytotrophoblast cells are exposed to T LYMPHOCYTES AND NATURAL KILLER (NK) cells which are two types of maternal immune cells in decidua, and therefore cytotrophoblast cells are potentially target of an immune attack. B. Production of PROSTOGLANDINS AND OTHER IMMUNESUPPRESANT substances secreted by DECIDUAL cells to inhibit the activation of T /NK cells in the endometrial stroma Secondly, Secretion of Interleukin-2 by leukocytes entering the endometrial stroma to prevent rejection of the embryo by the maternal tissue C. D. Despite the fact that chorionic villi cells are exposed to immune cells of the maternal tissue, the absence of major histocompatibility (MHC) antigens in the SYNCYOTROPHOBLAST DO NOT INITIATE TISSUE REJECTION Metabolism of the Placenta Substances transfer between the mother and the Fetus: 1. Water-Glucose 2. Cholesterol-Triglyceride 3. Amino Acids-Hormones-Electrolyte 4. Antibodies from mother (IgG) There is a 2-way transport of substances between the placenta and the mother and these are basically 4 types: 1. Passive transport by simple diffusion: oxygen -CO2 -water electrolytes 2. Facilitated diffusion : glucose 3. Active transport – amino acid ,vitamin 4. Pinocytosis-fat,complex proteins,Ig Placental Hormones and functions Syncytiotrophoblasts in the fetal placenta synthesize protein and steroid hormones a. The placenta provides the production of the hormones PROGESTERONE and ESTROGEN, which are involved in maintaining pregnancy. b. hCG (HUMAN CHORIONIC GONADOTROPIN) is synthesized in the second week that suppresses the menstrual cycle , ensures the continuation of the corpus luteum (corpus luteum of pregnancy). At the eighth week hormone reaches the highest level in c. d. e. the mother's blood and urine, then gradually decreases Chorionic somatotropin or placental lactogen Chorionic thyrotropin Chorionic corticotropin Placental Barrier and harmful substances Pregnancy and Rubella infection (Rubella syndrome) Rubella is a common viral infection. It can cause serious problems like Abartus and anomalia in the fetus during pregnancy. Infection is caused by direct contact with the secretions of the nose and mouth Deafness, Cataracts, Heart defects, hearing loss, Diabetes mellitis, brain disorders, Mental retardation,fetal growth restriction bone alterations, Liver and spleen damage. peripheral pulmonary stenosis narrowing in one or more of the branches of the pulmonary arteries 7 Toxoplasma Infection Toxoplasmosis is an infection with a parasite called Toxoplasma gondii ( most animals and birds ). Toxoplasmosis can cause miscarriages, dead or disabled births during pregnancy. People often get the infection from ; A. Eating undercooked meat or from contact with cat feces B. Organ transplantation or blood transfusion from an infected person The parasite can pass from placenta and reach to a baby during pregnancy. 1- Symptoms : 1. 2. 3. 4. Too much fluid in or around the brain, also called hydrocephalus. Severe eye infection. Irregularities in brain tissues. An enlarged liver or spleen. 2- Symptoms of severe disease vary ; 1. Problems with mental or motor skills. 2. Problems with thinking and learning 3. Blindness or other vision problems. 4. Hearing problems. 5. Seizures. 6. Heart disorders. Placenta Complications. Placenta previa: Abnormal insertion of the placenta in the uterine wall The placenta is next to the cervix but does not cover the opening. the placenta covers part of the cervical opening Risc factors that predispose women to this complications are : Uterine malformations Advanced maternal age Twin pregnancy or multiple pregnancy Having had several previous pregnancies the placenta covers the entire cervical opening Short time between two births Having had a previous cesarean delivery Uterine scars from previous abortions or surgeries Tobacco and cocaine abuse Placenta Accreta The placenta is adhered to the wall of the uterus. The placenta does not only adhere to the wall, but moves into the wall and is called 1. placenta accreta, 2. placenta increta 3. placenta percreta, respectively, according to the degree of this progression. Twin pregnancy Dizygotic Monozygotic Twins 9 week twins 1 2 3 Stages of Labor and Birth Clinically, there are 3 stages of childbirth Dilation of cervix (stage 1) Birth (stage 2) Delivery of Placenta (stage 3) Stages 1-2 9 Prenatal Diagnostic Techniques : Diagnostic Amniocentesis 1. 2. Applied in 15th and 18th weeks of pregnancy The needle no.22 is immersed along the abdominal and uterine walls of the mother to reach the chorion and amnion and 15-20 ml of amniotic fluid is taken up and biochemical and genetic analyses. 3. Genetic disorders such as Down Syndrome, Neural Tube Defects, Congenital Metabolic disorders are diagnosed with this method CHORIONIC VILLUS SAMPLE (CVS) g Ultrasonografi (renkli dopler) IVF (in vitro fertilization) ICSI (intracytoplasmic sperm injection) Thank you for attention Cardiovascular histology Prof.Dr. B.Zühal Altunkaynak AIMS 1. Wall structure of the heart 2. Cardiac muscle cell types 3. Wall structure of arterial and venous system vessels 4. Functional differentiation in the vessels Overview of the cardiovascular system (CVS) Transport system Blood and lymph fluid Cells; nutrients; waste products; hormones; antibodies Overview of the cardiovascular system (CVS) Blood vessels work in two directions Artery takes blood to tissue Vein carries blood from tissue to heart Lymph vessels work one way, collect the exess intercellular fluid from the stroma and empty to lymph sacs. Heart Wall  It is a muscular pump  Three layers  Epicardium  Outside layer  This layer is also called as the visseral pericardium  Connective tissue layer  Myocardium  Middle and thickest layer  Mostly cardiac muscle  Endocardium  Inner layer  Endothelium and subendocardial layer Heart Wall Myocardium Endocardium Epicardium Epicardium Outermost layer of the heart Composed of connective tissue with nerves, vessels, adipocytes and an outer layer of mesothelium Covers and protects the heart Myocardium Thickest layer of the heart Thickest in left ventricle because must pump hard to overcome high pressure of systemic circulation Right atrium the thinnest because of low resistance to back flow Consist of cardiac muscle cells = myocytes – Different from smooth or skeletal muscle cells due to placement of nuclei, cross striations, and intercalated disks Intercalated disks – Junctional complexes that contain fascia adherens, desmosomes, and gap junction to provide connection and communication. – Bind myocytes and allow ion exchange to facilitate electrical impulses to pass Cardiac Myocytes Oval, with central single nuclei It has a striated structure Cells have collaterals Intercalar disc is located between cells Some cardiocytes in the atria have secretory granules (ANF) Cardiac Myocytes Branching myocytes Central nuclei Fibers with Cross Striations Intercalated discs It is at the border where the heart muscle cells meet Includes multiple gap-junctions There are also fascia adherens and desmosomes It is also found at the border where Purkinje cells adjoin. Gap-junctions serve to speed up the message Endocardium Innermost layer Composed of: – Simple squamous epithelium (endothelium) – Connective Tissue – Subendocardium: in contact with cardiac muscle and contains small vessels, nerves, and Purkinje Fibers. Purkinje Fibers Impulse conducting fibers Large modified muscle cells – Cluster in groups together – 1-2 nuclei and stain pale due to fewer myofibrils AV bundle branches located in the subendocardial connective tissue Blood Vessels: The Vascular System  Taking blood to the tissues and back  Arteries  Arterioles  Capillaries  Venules  Veins The Vascular System Figure 11.8b Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide Blood Vessels:  Three layers (tunics)  Tunica intima  Endothelium  Tunica media  Smooth muscle  Controlled by sympathetic nervous system  Tunica externa  Mostly fibrous connective tissue Tunica intima It is the layer in contact with blood Consists of single layer of squamous cell layer (= endothelium) Basal lamina Loose connective tissue ENDOTELIUM 1.Provide an exceptionally smooth surface 2.Regulate hemostasis, leukocyte adhesion and leukocyte transmigration 3.Secrete types II, IV, and V collagens, lamin, endothelin, nitric oxide, and von Willebrand factor. SUBENDOTHELIAL LAYER A subendothelial layer lies immediately beneath the endothelial cells. It is composed of loose connective tissue and a few scattered smooth muscle cells, both arranged longitudinally. Beneath the subendothelial layer is an internal elastic lamina (rich from the elastin) that is especially well developed in muscular arteries. Tunica media Circularly located smooth muscle cells Elastic laminas between rows of smooth muscle cells Elastic laminas with pores (with windows) (for diffusion) Extracellular matrix (ECM) elements in T.media are produced by smooth muscle cells (eg elastic lamina) T.media is thicker in the arteries Larger muscular arteries have an external elastic lamina, which is more delicate than the internal elastic lamina and separates the tunica media from the overlying tunica adventitia. Tunica adventitia Loose connective tissue, the outermost layer of the vessel Collagen, elastic fibers ECM = produced by fibroblasts Vaza vasorum, nerve fibers, lymph vessels T. Adventitia is thicker in veins Tunika adventisia is also called "Tunika externa" Classification of the Vessels I. Arteries II. Veins III. Capillaries Elastic Arteries the aorta and its major branches Also called conductive vessels There are 40-70 layers of the muscle cells and more elastic laminae Function: Keeping blood pressure constant in the arterial system Elastic Arteries Diameter:> 10 millimeters (mm) T. intima: endothelium, connective tissue, smooth muscle and elactic laminae T. media: smooth muscle, elastic lamellas T. adventitia: connective tissue; elastic fibers; Thinner than T.media; vaza vazorums extend to T.media Largest, conducting arteries – lead directly from heart, subject to high pressures Superior & inferior vena cava and their tributaries Pulmonary trunk & aorta and their major branches Vasa vasorum. Walls of the larger vessels, as the aorta, contain in the tunica adventitia a supply of microvasculature to bring O2 and nutrients to local cells too far from the lumen to be nourished by blood there. These arterioles (A), capillaries and venules (V) constitute the vasa vasorum (vessels of vessels). The adventitia of large arteries is also supplied more sparsely with small sympathetic nerves (N) for control of vasoconstriction. X100. H&E. Muscular Arteries Medium diameter arteries Also called distributive arteries They are the vessels that deliver blood to the organs Their diameters are variable Most anatomically named arteries are muscular arteries. Muscular Arteries Diameter: 2 - 10 mm T.intima: Endothelium Basal lamina Membrana elastica interna (most prominent) T.media: Smooth muscle Collagen fibers Elastic fibers (less than elastic artery) Membrane elastica externa (prominent in large muscular arteries) T.adventitia: Connective tissue Elastic fibers (less) Thinner than T.media ARTERIOLES Diameter: 10 - 100 µm (micrometers) T.intima: Endothelium basal lamina Connective tissue T.media usually consists of one or two layers of smooth muscle cells arranged in a spiral. No outer elastic lamina T.adventitia: Thin Difficult to differ from the connective tissue sheath  They are Resistance vessels VEINS Veins are capacitance vessels At any time, approximately 70% of the blood (circulating in the veins) is in the veins Veins begin with the postcapillary venule Postcapillary venules Diameter: 10 – 50 µm T. İntima: – Endothelium – Basal lamina – Pericytes: » Contractile » Can divide » May differ T.media: Ø T.adventitia: Ø Small Veins Medium-Sized Veins Large Veins Capillaries  Arising from the terminal ends of the arterioles are capillaries which form, by branching and anastomosing, a capillary bed (network) between the arterioles and the venules.  Electron micrographs have revealed three types of capillaries: (1) continuous, (2) fenestrated, and (3) sinusoidal General Structure of Capillaries  These endothelial cells are flattened, with the attenuated ends tapering to a thickness to 0.2 µm or less, although an elliptical nucleus bulges out into the lumen of the capillary.  The cytoplasm contains a Golgi complex, a few mitochondria, some rough endoplasmic reticulum (RER), and free ribosomes Continuous Capillaries  Continuous capillaries have no pores or fenestrae in their walls.  Continuous capillaries are present in muscle, nervous, and connective tissues, whereas in the brain tissue they are classified as modified continuous capillaries.  The intercellular junctions between their endothelial cells are a type of fasciae occludentes, which prevent passage of many molecules. In continuous capillaries, basal lamina covers the endothelium and surrounding pericyte cells PERICYTES: The origin is plurıpotent stem cells according to the vessel type and specifically depending on injury or growth factors; it turns into endotel cell fibroblasts Smooth muscle cell Fenestrated Capillaries  Fenestrated capillaries have pores (fenestrae) in their walls that are 60 to 80 nm in diameter and covered by a pore diaphragm.  These capillaries are found in the pancreas, intestines, and endocrine glands.  The pores in fenestrated capillaries are bridged by an ultrathin diaphragm.  An exception is the renal glomerulus, composed of fenestrated capillaries that lack diaphragms. diaphragms. glomerulus Sinusoidal Capillaries  Sinusoidal capillaries may possess discontinuous endothelial cells and basal lamina and contain many large fenestrae without diaphragms, enhancing exchange between blood and tissue.  The vascular channels in certain organs of the body, including the bone marrow, liver, spleen, lymphoid organs, and certain of the endocrine glands, are called sinusoids, irregular blood pools or channels that conform to the shape of the structure in which they are located. Thank you………… RESPIRATORY SYSTEM Lecturer Ceren ERDEM ALTUN [email protected] 07.03.2024 → Must be able to describe the basic wall structure of the airways from the nose to the alveoli. → Must be able to explain the functions of respiratory tract mucosa and mucus. GOALS → Be able to list the layers that make up the respiratory membrane. → Be able to explain cell types and functions in the alveolar epithelium. RESPIRATORY SYSTEM FUNCTIONS ✓ Transport of oxygen to cells, removal of CO2 ✓ Heating of inhaled air (by the veins near the surface and by turbulence in the turbinates(conchae) ✓ Humidification of inhaled air (with serous glands) ✓ Removal of particles from inhaled air (with mucus and kinocilium) ✓ Immune protection (with lymphoid Tissue and macrophages) ✓ Olfactory (olfactory epithelium) ✓ Voice creation (real and fake vocal cords) ANATOMY OF THE RESPIRATORY SYSTEM CONDUCTING PORTION RESPIRATORY PORTION ❑ The respiratory system is functionally examined in 2 parts; 1) CONDUCTING PORTION - nasal cavity - nasopharynx (throat) - larynx (larynx) - trachea - bronchi - bronchiole and terminal bronchiole → It cleans and moistens the inhaled air and creates a passage through which air travels to and from the lungs. → Cartilage, elastic and collagen fibers, and smooth muscles in the conductor section provide the necessary bendability, extensibility and structural support ❑ The respiratory system is functionally examined in 2 parts; 2) RESPIRATORY PORTION - respiratory bronchioles - alveolar ducts - alveoli → The part where gas exchange occurs between air and blood. →Alveoli; They are sac-like structures that make up a large part of the lungs, where O2 and CO2 exchange between inhaled air and blood takes place. NASAL CAVITY Nasal skin is a keratinized stratified squamous epithelium that enters through the nostrils and progresses to the vestibule. This skin contains sweat glands, sebaceous glands, and wet and thick nasal hairs that trap large particles in the inhaled air. In the vestibule, the epithelium loses its keratin structure and turns into the typical pseudostratified columnar ciliated epithelium of the respiratory system before entering the nasal cavities. The front part of the nose is supported by cartilages, and the back part is supported by cartilages and bones. Nasal pits are located within the skull as two chambers separated by the nasal septum. There are 3 bony protrusions called turbinates (conchae) on the side wall of each chamber. The middle and lower turbinate are covered with RESPIRATORY EPITHELIUM, the roof of the nasal fossa and the upper turbinate are covered with specialized OLFACTORY EPITHELIUM NASOPHARYNX The nasal cavity is adjacent to the nasopharynx from behind via the turbinates. Turbinates(conchae); They increase the surface area and contribute to the heating and humidification of inhaled air by creating turbulence. 1) VESTIBULE It is the part of the nose that opens to the outside environment. It is lined with stratified squamous epithelium, which is a continuation of the facial skin. It contains numerous VIBRISSA (nasal hairs) that trap large particles entering with inhaled air. The secretions of the sebaceous glands it contains also help capture particles. at the point where the vestibule ends, the epithelium becomes thinner and turns into pseudostratified columnar ciliated epithelium, which is specific to the respiratory region. MIDDLE AND LOWER CHONCAE RESPIRATORY EPITHELIA UPPER CHONCAE OLFACTORY EPITHELIA 2) RESPIRATORY PORTION It constitutes the majority of the nasal cavity volume. 2) RESPIRATORY PORTION pseudostratified columnar ciliated epithelium Basal membrane LAMINA PROPRIA MUCOSA = EPITHELIA + LAMINA PROPRIA EPITHELIA LAMINA PROPRIA →It consists of loose connective tissue with a rich vascular network. → The arrangement of the veins ensures that the inhaled air is heated by the flowing blood. These veins become overfilled and leak during colds, allergic reactions or viral infections. Lamina propria swells with fluid accumulation. As a result, swelling of the mucous membrane limits air passage and breathing difficulties occur. →The mucus layer produced by the glands and goblet cells traps airborne particles. →IgA secreted from plasma cells in the lamina propria plays a role in local defense. THERE ARE 5 TYPES OF CELLS IN THE RESPIRATORY EPITHELIA AND EACH SIT ON THE BASAL MEMBRANE!!! 1. 2. 3. 4. 5. Columnar ciliated cells; is the most abundant, 250-300 hairs on the apical surface Goblet cells; more dense in some areas, nucleus located basally, secretory granules apically Brush cells; a small number of prismatic cells, vestigial microvilli, and chemosensory (chemical sensing) receptors. Kulchitsky cells; cells of the neuroendocrine system containing dense granules Basal cells; Stem and precursor cells capable of mitosis G: Goblet cell arrow: mucus accumulations 3) OLFACTOR PORTION THERE ARE 3 TYPES OF CELLS IN THE OLFACTOR EPITHELIA!!! 1. Olfactory receptor cell 2. Supporting cell 3. Basal cell OLFACTORY NEURON → bipolar neurons → Their nuclei form an irregular row in the central part of the epithelium.. → The extensions facing the apical (lumen) are dendrite tips. → Long cilia extend from the basal bodies, which are immobile but serve to increase the surface area for chemoreceptors. SUPPORTING CELL →They are long thin prismatic cells extending from basal to apical. →The nuclei at the top of the epithelium are the support cell nuclei. →There are plenty of microvilli on their surface. →They provide mechanical and metabolic support to olfactory cells. →Proteins that bind odor molecules are secreted from these cells. BASAL CELLS → They are small, round or coneshaped cells close to the basal lamina. → Every 2-3 months they replace olfactory neurons and, less frequently, supporting cells. BASAL CELLS The Lamina Propria of the olfactory epithelium contains the olfactory glands, which are large serous glands that facilitate the entry of new odorants by providing a constant flow of fluid around the olfactory hairs; Bowman’s gland Supporting cells Olfactory epithelia Lamina propria SC: supporting cell OC: olfactory cell BC: basal cell NASOPHARYNX NASOPHARYNX The nasal cavities open into the nasopharynx, the first part of the pharynx. The nasopharynx continues caudally with the oropharynx (throat). This structure opens into the larynx and esophagus. The epithelium is a respiratory epithelium similar to the nasal cavity epithelium. LARYNX It is a short (4cmx4cm) air passage located between the pharynx and trachea. Hard wall; Large cartilages (thyroid, cricoid, arytenoid) are hyaline type. Small cartilages (epiglotte, cuneiform, corniculate) are elastic type. Cartilages in the structure; They play a role in keeping the airway open, preventing food from entering the trachea, and producing sound. LARYNX G: seromucous gland LV: larynx vestibules VF: vestibüler fold V: ventricle VC: vocal cords VM: striated vocalic muscles EPIGLOTTIS It is a flat structure that protrudes from the upper part of the larynx. It prevents swallowed food or liquid from entering the trachea. EPIGLOTTIS → The side facing the tongue is stratified squamous epithelium; It turns into respiratory epithelium at different points of the laryngeal surface. There are mixed serous and mucous glands in the lamina propria beneath the epithelium. TRACHEA It contains approximately 12 C-shaped hyaline cartilage rings. It strengthens the wall and ensures that the tracheal lumen remains open. The open ends of the cartilage rings are directed towards the esophagus on the back side of the trachea, and they are joined by a smooth muscle bundle called tracheal muscle and fibroelastic tissue attached to the pericondrium. The entire organ is surrounded by adventitia. The trachea, 10–12 cm long in adults, is lined with typical respiratory mucosa in which the lamina propria contains numerous seromucous glands that produce watery mucus. The trachea is completely lined with respiratory epithelium and supported by C-shaped rings of hyaline cartilage between the submucosa and adventitia, strengthening the wall and keeping the tracheal lumen open. It is a tube with 3 layers: mucosa, submucosa and adventitia. Divides into 2 primary bronchi SUBMUCOSA MUCOSA LAMINA PROPRIA BASAL MEMBRANE RESPIRATORY EPITHELIUM LAMINA PROPRIA It is loose connective tissue. There are many fibroblasts, lymphocytes, plasma cells, mast cells, eosinophils and abundant blood vessels. Collagen and elastic fibers condense in their depths and form a fibroelastic region. SUBMUCOSA It has the feature of loose connective tissue. There are many seromucous glands CARTILAGE: The submucosa continues with the perichondrium of the underlying hyaline cartilage. ADVENTITIA It is loose connective tissue that contains blood vessels and nerves. MUCOSA SUBMUCOSA ADVENTITIA BRONCHIAL TREE AND LUNG The trachea branches and divides into 2 to form the primary bronchus. (accompanied by arteries, veins and lymph vessels) After entering the lungs, the bronchi divide into 3 secondary bronchi in the right lung and 2 secondary bronchi in the left lung.. The secondary bronchi branch again and form the tertiary bronchi. Each of the tertiary bronchi divides into smaller branches and forms the bronchopulmonary segment. This structuring; It allows surgical resection of diseased lung tissue without damaging adjacent healthy tissue. The diameter of the tertiary bronchi gradually decreases and they branch to form bronchioles. Each bronchiole enters the pulmonary lobule and forms 5-7 terminal bronchioles and continues as respiratory bronchioles. Cartilaginous rings turn into cartilage plates as the diameter of the bronchi decreases. When it reaches the bronchioles, it disappears. BRONCHI E: respiratory epithelia SM: smooth muscle C: hyaline cartilage B:seromucous glands V: vein SEGMENTAL BRONCHI BRONCHIOLES There is tight connective tissue and smooth muscle, but there are no glands and cartilage structures. In larger bronchioles the epithelium is still pseudostratified ciliated columnar epithelium. However, as you move towards the terminal bronchioles, which are the last parts, the size and complexity decrease and the epithelium turns into single-layered columnar and singlelayered cuboidal epithelium. BRONCHIOLES In very small bronchioles, the epithelium descends and turns into a singlelayered fibrillar cuboidal epithelium. Several layers of smooth muscle, indicated by arrows, make up the bulk of the wall. TERMINAL BRONCHIOLES They are the last parts of the air conduction system before the gas exchange zones. It contains 1 or 2 layers of smooth muscle cells surrounded by connective tissue. The epithelium consists of cuboidal epithelial cells with cilliated and low prismatic cells (clara cells) that do not contain cilia. TERMINAL BRONCHIOLES CLARA CELLS: Cells that do not contain cillia, have a domeshaped apical surface, and have secretory granules in their cytoplasm. CLARA CELLS; Clara - secretes surfactant, which reduces s