Review Embryology Block-1 PDF

Review block-1 Lectures Fall Semester 2024 Dr. Ismail Memon MBBS, PhD Saba University School of Medicine  Important syndrome due to numerical chromosomal abnormalities Trisomy of autosomes – Trisomy 21 or Down syndrome –...

Review block-1 Lectures Fall Semester 2024 Dr. Ismail Memon MBBS, PhD Saba University School of Medicine  Important syndrome due to numerical chromosomal abnormalities Trisomy of autosomes – Trisomy 21 or Down syndrome – Trisomy 18 or Edwards syndrome – Trisomy 13 or Patau syndrome Trisomy of sex chromosome – Klinefelter syndrome 47, (XXY) – Triple X syndrome 47, (XXX) Monosomy – Turner syndrome 45, (XO) Dr. Ismail 2  Syndrome due to numerical chromosomal abnormalities Klinefelter Syndrome Klinefelter syndrome is a genetic condition that results when a boy is born with an extra copy of the X chromosome, it isn’t often diagnosed until adulthood. The cells have 47 chromosomes with a sex chromosomal complement of the XXY type. The clinical features of Klinefelter syndrome, found only in males with sterility, testicular atrophy, hyalinization of the seminiferous tubules, longer limbs, and usually gynecomastia. Dr. Ismail 3  LO- Triple X syndrome 6 Occur due to an extra copy of the X chromosome in oocyte or sperm (47, XXX). It affects about 1 in 1,000 females. Many girls and women with triple X syndrome don't experience symptoms or have only mild symptoms. Patients with triple X syndrome are infantile, with scanty menses and some degree of mental retardation. Patients with triple X syndrome often go undiagnosed because of their mild physical features. However, these girls frequently have problems with speech and self- esteem. Dr. Ismail 4 Memon  Syndrome due to numerical chromosomal abnormalities Monosomy Turner syndrome, with a 45, X karyotype, is the only monosomy compatible with life. Even then, 98% of all fetuses with the syndrome are spontaneously aborted. The few that survive are unmistakably female in appearance and are characterized by the absence of ovaries and short stature. Other common associated abnormalities are webbed neck, lymphedema of the Dr. Ismail 5  LO- Structural chromosome 6 abnormalities In some cases, the broken piece of a chromosome is lost, and the infant with partial deletion of a chromosome is abnormal e.g. Cri-du-chat syndrome. Cri-du-chat syndrome.  Caused by partial deletion of the short arm of chromosome 5  Affected children have a cat-like cry, microcephaly, mental retardation, and congenital heart disease.. Dr. Ismail  LO- Microdeletion 6 syndrome Sometimes only a few contiguous genes are deleted. Microdeletion on the maternal chromosome 15 causes Angelman syndrome. Children are mentally retarded, cannot speak, exhibit poor motor development, and are prone to unprovoked and prolonged periods of laughter. Microdeletion on the paternal chromosome 15 causes Prader-Willi syndrome. Affected individuals are characterized by Dr. Ismail 7 hypotonia, obesity, mental retardation,  LO- 6 Fragile X syndrome Caused by mutation in FMR1 gene (fragile X mental retardation 1). – Normally, FMR1 gene makes a protein needed for brain to grow properly. A defect in this gene makes body produce too little of the protein, or none at all.  Characterized by mental retardation, large ears, prominent jaw, and pale blue irises.  Boys and girls can both be affected, but because boys have only one X chromosome, a single fragile X is likely to affect them more severely. Dr. Ismail 8 Primordial germ cells Primordial germ cells (PGCs) are the precursors of sperms and eggs, which generate a new organism that can create endless new generations through germ cells. In other words, we can also say that primordial germ cells matures to form male and female gametes. LO- 9 Dr. Ismail  Gametogenesis We will start to describe the origin of germ cells from the beginning to the end: A sperm will fertilize the ovum in the fallopian tube and form the zygote. A zygote will move in the fallopian tube and become a blastocyst then reach the uterus with a group of cells inside of it called the inner cell mass. The blastocyst is implanted in the endometrium of the uterus and the inner cell mass will start dividing and form a disc of two layers. 10 Dr. Ismail  During the 2nd week of development, some cells of the epiblast which are programmed to become primordial germ cells will migrate from the epiblast towards the yolk sac and wait for signal. During 5th week the primordial germ cells will become activated and migrate from the yolk sac to the genital ridge. In the genital ridge the germ cells will divide to increase the number and all of them are diploid. (44 and XY chromosomes). The somatic cells in the genital ridge and the primordial germ cells form the testes or ovary. The primordial germ cell will reside in the 11 Dr. Ismail Oogenesis Oogenesis is the process whereby oogonia differentiate into mature oocytes. Maturation of oocytes begins before birth. Once PGCs have arrived in the gonad, they differentiate into oogonia. In the ovary, these cells undergo several mitotic divisions and the majority of oogonia continue to divide by mitosis, but some of them arrest Dr. Ismail Oogenesis During the next few months, oogonia increase rapidly in number followed by cell death. By the seventh month, the majority of oogonia have degenerated except for a few near the surface. All surviving primary oocytes have entered prophase of meiosis I, and most of them are individually surrounded by a layer of flat follicular epithelial cells. A primary oocyte, together with its surrounding flat epithelial cells, is Dr. Ismail Oogenesis Near the time of birth, all primary oocytes have started prophase of meiosis I. The total number of primary oocytes at birth is estimated to vary from 600,000 to 800,000 Primary oocytes remain arrested in prophase-1 until puberty is reached. This arrested state is produced by oocyte maturation inhibitor (OMI), a small peptide secreted by follicular cells. During childhood, most oocytes become atretic; only approximately 40,000 are present by the beginning of puberty, and fewer than 500 will be ovulated. Dr. Ismail Oogenesis Maturation of oocytes continues at puberty. At puberty, each month, 15 to 20 follicles selected from this pool begin to mature. Some of these die, whereas others begin to accumulate fluid thereby entering the antral or vesicular stage. Immediately prior to ovulation, follicles are quite swollen and are called mature vesicular follicles or graafian follicles. The antral stage is the longest, whereas the mature vesicular stage encompasses approximately 37 hours prior to ovulation. LH Dr. Ismail Oogenesis Preparation for ovulation The cell then enters meiosis II but arrests in metaphase approximately 3 hours before ovulation. Meiosis II is completed only if the oocyte is fertilized; otherwise, the cell degenerates approximately 24 hours after ovulation. At the completion of the oogenesis (meiosis II), Three viable mature oocyte and one polar body Dr. Ismail LO- Dr. Ismail  Ovulation Ovarian cycle: Preparation for ovulation At puberty, the female begins to undergo regular monthly cycles. These sexual cycles are controlled by the Gonadotropin- releasing hormone (GnRH) from hypothalamus. GnRH acts on the anterior pituitary gland and secrete the follicle-stimulating hormone (FSH) and luteinizing hormone (LH) which stimulate and control cyclic changes in the ovary. At the beginning of each ovarian cycle, 15 to 20 primary-stage (preantral) follicles are stimulated to grow under the influence of FSH. LO- Dr. Ismail Zygote formation The definitive oocyte contains the female pronucleus which has 23 chromosomes. The tail of the sperm detaches, and its nucleus will enter the cytoplasm of the definitive oocyte as the male pronucleus carrying 23 chromosomes. Both male and female pronuclei are morphologically indistinguishable, come close to each other, unite, and restore the diploid number of chromosomes and a zygote is What are formed. the end results of fertization : 1- Restoration of the diploid number of the chromosome 2- Determination of the sex of the new individual LO- Dr. Ismail Cleavage and blastocyst formation: The zygote divide to become two cells, then the cleavage continues until a morula is formed which consists of 16 cells. Cells of the morula will differentiate into the outer cell mass and inner cell mass. Intercellular spaces will be formed and finally they unite to form a single cavity called blastocele, at this time the embryo is called the blastocyst. Blastocyst will enter the uterine cavity, but it is still surrounded by the zona pellucida which will prevent implantation. The blastocyst will digest the zona pellucida by trophoblastic enzymes and it will come out of it in a process called hatching. A matureLO- blastocyst consists of: Inner cell mass (embryoblast), outer cell mass Dr. Ismail Stages of human embryo development up to the hatching of the blastocyst Hatching out embryo  Blastocyst formation  Embryonic pole  Side of blastocyst to which inner cell mass is attached  Abembryonic pole  Opposite side LO- 22 Dr. Ismail  LO-1 At the end of 1 week st At the end of 1st week embryo has inner cell mass and outer cell mass. Inner cell mass, the Embryoblast forms the embryo proper. Outer cell mass, the Trophoblast will contribute to formation of placenta. 23 Dr. Ismail Memon  Further development of LO-2 embryoblast The inner cells, the embryoblast differentiates in: Dorsal epiblast layer (columnar cells) and ventral hypoblast layer (cuboidal cells). Within the epiblast, clefts begin to develop and eventually coalesce to form amniotic cavity. The amniotic cavity will eventually become filled with amniotic fluid. 24 Dr. Ismail  Further development of LO-3 embryoblast Epiblast cells adjacent to the cytotrophoblast are called amnioblasts. Hypoblast cells migrate, lines the blastocyst cavity and form exocoelomic membrane. Blastocyst cavity is now called exocoelomic cavity or primary yolk sac. Epiblast and hypoblast together form a flat disk known as bilaminar disc. 25 Dr. Ismail Week 2 Summary Dr. Ismail  Clinical Considerations LO-6 Human chorionic gonadotropin (hCG)  Glycoprotein produced by syncytiotrophoblast.  Stimulates production of progesterone by corpus luteum.  Assayed in maternal blood at day 8 or maternal urine at day 10  Basis of pregnancy testing and detectable throughout pregnancy  Low hCG may predict a spontaneous abortion or may indicate an ectopic pregnancy  High hCG may indicate a multiple pregnancy, hydatidiform mole, or gestational trophoblastic neoplasia. 27 Dr. Ismail  LO-7 Gestational trophoblastic disease Hydatidiform mole / Molar pregnancy – Marked benign enlargement of chorionic villi (trophoblast). – Characterized by grapelike vesicles in uterus and absence of embryo, high hCG level. Gestational trophoblastic neoplasia - choriocarcinoma – Malignant tumor of trophoblast that may occur after normal or ectopic pregnancy, abortion, or hydatiform mole. – Sometimes they metastasize to liver 28 Dr. Ismail  LO-7 Oncofetal antigens Cell surface antigens (proteins), normally present during fetal development. For unknown reasons re-express themselves in human malignant cells. Used as tumor markers for diagnosis & treatment prognosis. – e.g., alpha-fetoprotein, which is produced by hepatocellular carcinoma and some germ cell tumors – Carcinoembryonic antigen, which is elevated in people with colon cancer. – Beta 2 microglobulin in multiple myeloma.  Gastrulation, formation of the trilaminar LO- 1 embryonic disc Gastrulation is the conversion of the bilaminar disc into a trilaminar embryonic disc consisting of ectoderm, mesoderm, and endoderm. Gastrulation begins with the formation of the primitive streak in the epiblast followed by differentiation of the epiblast to endoderm and mesoderm and then its name changes from epiblast to ectoderm. Dr. Ismail Memon Formation of Primitive Streak LO- 2 The primitive streak is a linear band of thickened epiblast formed by proliferation of the epiblast cells and migration toward the midline. The cell migration, invagination and specification in the primitive streak are controlled by FGF8, which is synthesized by streak cells themselves. As the primitive streak elongates its cranial end forms the primitive node. A groove appears in the primitive streak and the primitive nodes and their name changes to the primitive groove and primitive pit. Formation of the primitive groove is the beginning of gastrulation. Dr. Ismail Memon  LO-2 Functions of the primitive streak The primitive streak is important for the determination of: 1. Determination of the site of gastrulation. 2. Initiation of formation of germ layers. 3. Defining major body axes. Fate of the primitive streak: 1- The primitive streak gradually diminishes in size and becomes insignificant structure in the sacro- coccygeal region of the embryo and normally disappear by the end of the 4th week. sacrococcygeal teratoma. Dr. Ismail Memon  Clinical Corelates Tumors Associated with Gastrulation Sacrococcygeal teratomas Sometime, remnants of the primitive streak persist in the sacrococcygeal region. These clusters of pluripotent cells proliferate and form tumors, known as sacrococcygeal teratomas, which commonly contain tissues derived from all three germ layers. Birth Defects Associated with Laterality Situs inversus refers to a condition where the positioning of all organs is reversed in a mirror image arrangement. E.g., inversions (i.e., the two ventricles in the heart are reversed). Dr. Ismail Memon  Clinical CorelatesLO-9 Teratogenesis Associated with Gastrulation Third week of development, when gastrulation is initiated, is a highly sensitive stage for teratogenic insult. At this time, fate maps for various organ systems, may be damaged by teratogens. In animals, high doses of alcohol at this stage kill cells in the anterior midline of the germ disc, producing a deficiency of the midline in craniofacial structures and resulting in holoprosencephaly. In such a child, the forebrain is small, the two lateral ventricles often merge into a single ventricle, and the eyes are close together (hypotelorism). Dr. Ismail Memon LO- 2 During the 2nd week of development, some cells of the epiblast which are programmed to become primordial germ cells will migrate from the epiblast towards the yolk sac and wait for signal. During 5th week the primordial germ cells will become activated and migrate from the yolk sac to the genital ridge. In the genital ridge the germ cells will divide to increase the number and all of them are diploid (44 and XY chromosomes). The somatic cells in the genital ridge and the primordial germ cells form the testis or ovary. 35 Dr. Ismail  Neurulatio LO-1 Neural tube formation n Neurulation is the process whereby the neural plate forms the neural tube. Neural plate and body axis lengthen. As the neural plate lengthens, its lateral edges elevate to form neural folds, and the depressed midregion forms the neural groove. Gradually, the neural folds approach each other in the midline, where they fuse. Fusion begins in the cervical region (fifth somite) and proceeds cranially and caudally. As a result, the neural tube is formed. The cephalic and caudal ends of the neural tube communicate with the amniotic cavity by 36 Dr. Ismail  Neurulation LO-1 The neural tube communicate with the amniotic cavity by way of the anterior (cranial) and posterior (caudal) neuropores. Closure of the cranial neuropore occurs at approximately day 25 (18- to 20-somite stage), whereas the posterior neuropore closes at day 28 (25-somite stage). Neurulation is then complete, and the central nervous system is represented by a closed tubular structure with a narrow caudal portion, the spinal cord, and a much broader cephalic portion, the brain vesicles. Upregulation of fibroblast growth factor (FGF) 37 Dr. Ismail  Failure of the closing of LO-2 neuropores. Neural Tube Defects Neural tube defects result when neural tube closure fails to occur. If the neural tube fails to close in the cranial region, the defect is called anencephaly. If closure fails anywhere from the cervical region caudally, then the defect is called spina bifida. The most common site for spina bifida to occur isGetting in the enough lumbosacral folic region. acid, a type of vitamin B, before and during pregnancy prevents most neural tube defects. Dr. Ismail  LO- Placenta 2 The placenta is a temporary organ that forms in uterus during pregnancy. It attaches to uterine wall and provides nutrients and oxygen to baby in the womb through the umbilical cord. It has two parts: 1. Maternal part - Decidua basalis 2. Fetal part - Chorion frondosum 39 Dr. Ismail  LO- 3 Maternal part of placenta –Decidua (shed or sloughed off) Uterine endometrium after implantation is called decidua. Types decidua: 1. Portion of decidua where placenta is to be formed is called decidua basalis. 2. Part of decidua that separates embryo from uterine lumen is called decidua capsularis. 3. Part lining rest of uterine cavity is called decidua parietalis (vera). 40 Dr. Ismail  LO- Fetal part of placenta- Chorion 3 frondosum Formation of chorionic villi Functional unit of placenta is called villi. First, they are formed as offshoots from all over the surface of trophoblast – chorion. Villi related to decidua capsularis degenerate, chorion becomes smooth and is called chorion laeve. Villi related to decidua basalis proliferate and form placenta, this part of chorion is called chorion frondosum. 41 Dr. Ismail  Twinning LO-8 Dizygotic Twins Dizygotic (fraternal) twins results from fertilization of two different secondary oocytes by two different sperms. Approximately 90% of twins are dizygotic, and their incidence increases with maternal age. The two zygotes have totally different genetic constitutions. They may or may not be of different sex. The zygotes implant individually in the uterus, and usually each develops its own placenta, 42  Twinning LO-8 Monozygotic twins Monozygotic (identical) twins results from fertilization of one secondary oocyte by one sperm. Resulting zygote split at different stages of development. Twins are genetically identical 43 Dr. Ismail Splitting of the zygote may LO-8 occur at different stages: Splitting of zygote at two cell stage: 2 placentas, 2 chorionic sacs, 2 amniotic sacs. 35% case, develop like dizygotic twins. Splitting of zygote at early blastocyst stage: 1 placenta, 1 chorionic sac, 2 amniotic sac. 65% case Splitting at bilaminar germ disc (just before primitive streak ) stage: Incomplete division of inner cell mass 1 placenta, 1 chorionic sac, 1 amniotic sac. Dr. Ismail 44  LO-8 Vanishing twins One partner usually dies in the first trimester, and is compressed & mummifies - fetus papyraceus Cause of vanishing twins: – Twin transfusion syndrome The term vanishing twin refers to the death of one fetus. This disappearance, which occurs in the first trimester or the early second trimester, may result from resorption or formation of a fetus papyraceus. 45 Dr. Ismail  LO-8 Twin transfusion syndrome  Usually occur in monozygotic twins which share common placenta Vascular placental anastomoses  the connecting blood vessels within the placenta allow blood to pass from one twin to the other  allows one twin to receive more blood than the other. 46 Dr. Ismail  LO- Striated Skeletal Muscles 4 Some cells from the VLL region also migrate into the adjacent parietal layer of the lateral plate mesoderm. Here they form infrahyoid (neck muscles), abdominal wall (rectus abdominis, internal and external oblique, and transversus abdominis), and limb muscles (abaxial or hypaxial). The remaining cells in the myotome form muscles of the back, shoulder girdle, and intercostal muscles (primaxial or epaxial). In humans, the erector spinae, the transversospinales, the splenius and suboccipital muscles are the epaxial muscles. Each myotome receives its innervation from spinal nerves derived from the same segment as the muscle cells. Dr. Ismail Developmental origin of muscles  LO- Limb Defects 10 Amelia: Complete absence of one or more of the extremities. Meromelia: Partial absence of one or more of the extremities. Micromelia: Sometimes, all segments of the extremities are present but abnormally short. Brachydactyly: Sometimes, the digits are shortened. Syndactyly: If two or more fingers or toes are fused. Dr. Ismail  Polydactyly? Polydactyly is a condition in which a baby is born with one or more extra fingers. It is because of abnormal duplication of the zone of polarizing activity (ZPA).  LO- Limb Defects 10 Cleft hand and foot consists of an abnormal cleft between the second and fourth metacarpal/metatarsal bones and soft tissues. The third metacarpal and phalangeal bones are almost always absent, and the thumb and index finger and the fourth and fifth fingers may be fused. Dr. Ismail  LO- Limb Defects 10 Arthrogryposis Arthrogryposis (congenital joint contractures) usually involves more than one joint. May be caused by: Neurological defects (motor horn cell deficiency, meningomyelocele). Muscular abnormalities (myopathies, muscle agenesis) Joint and contiguous tissue problems (synostosis, abnormal development). Clubfoot may be caused by arthrogryposis. Dr. Ismail  LO- Limb Defects 10 Amniotic bands Amniotic bands may cause ring constrictions and amputations of the limbs or digits. The origin of the bands is not clear, but they may represent adhesions between the amnion and affected structures in the fetus. The bands may originate from tears in the amnion that detach and surround part of the fetus. Dr. Ismail  Clinical corelates Preeclampsia Preeclampsia is a leading cause of maternal mortality in the United States. Preeclampsia is a condition characterized by maternal hypertension and proteinuria due to reduced organ perfusion and occurs in approximately 5% of pregnancies. Preeclampsia begins suddenly anytime from approximately 20 weeks’ gestation to term and may result in fetal growth retardation, fetal death, or death of the mother. The condition may progress to eclampsia, which is characterized by seizures. Dr. Ismail