Embryology and Gametogenesis 2023 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