GENERAL EMBRYOLOGY embrology notes111.pptx

Good notes

1. GENERAL EMBRYOLOGY Sigei Caroline

2. Outline Terminologies Molecular regulation and signaling Gametogenesis First week of development Second week of development Third week of development Fourth to eighth week of development Body cavities Third month to birth (fetus and the placenta) Teratology &prenatal diagnosis

3. What is Embryology? study of embryos prenatal development of embryos and fetuses. Developmental anatomy is the field of embryology concerned with the changes that cells, tissues, organs, and the body as a whole undergo from a germ cell of each parent to the resulting adult. Teratology (Gr. teratos , monster) is the division of embryology and pathology that deals with abnormal development (birth defects).

4. SIGNIFICANCE OF EMBRYOLOGY Bridges the gap between prenatal development and obstetrics, perinatal medicine, pediatrics, and clinical anatomy. Develops knowledge concerning the beginnings of human life and the changes occurring during prenatal development. Is of practical value in helping to understand the causes of variations in human structure. Illuminates gross anatomy and explains how normal and abnormal relations develop .

5. objectives To help understand how normal development occurs from conception to birth. To understand the principle of teratogenesis and the basis of birth defects To understand the developmental basis in the study and practice of medicine

6. Introduction to developing human Human development is a continuous process begins when an oocyte (ovum) from a female is fertilized by a sperm (spermatozoon) from a male. Cell division, cell migration, programmed cell death, differentiation, growth, and cell rearrangement transform the fertilized oocyte, a highly specialized, totipotent cell, a zygote , into a multicellular human being. NB; Development does not stop at birth.

7. Developmental periods prenatal (before birth) postnatal (after birth) periods most visible advances occur during the third to eighth weeks of embryonic development differentiation and growth of tissues and organs occur during fetal period. The rate of body growth increases during this period.

8. Terms used in embryology Oocyte ( L. ovum , egg)-is the female germ or sex cells produced in the ovaries . When mature, the oocytes are called secondary oocytes or mature oocytes. Sperm (Gr. sperma , seed).- or spermatozoon, refers to the male germ cell produced in the testes (testicles). Numerous sperms (spermatozoa) are expelled from the male urethra during ejaculation. Zygote -is the cell that results from the union of an oocyte and a sperm during fertilization. A zygote or embryo is the beginning of a new human being. Cleavage - is the series of mitotic cell divisions of the zygote that result in the formation of early embryonic cells, blastomeres . The size of the cleaving zygote remains unchanged because at each succeeding cleavage division, the blastomeres become smaller.

9. Morula (L. morus , mulberry)-is a solid mass of 12 to approximately 32 blastomeres formed by cleavage of a zygote. The blastomeres change their shape and tightly align themselves against each other to form a compact ball of cells. This phenomenon, compaction , is probably mediated by cell surface adhesion glycoproteins. The morula stage occurs 3 to 4 days after fertilization, just as the early embryo enters the uterus. Blastocyst (Gr. blastos , germ + kystis , bladder). After 2 to 3 days, the morula enters the uterus from the uterine tube (fallopian tube). Soon a fluid-filled cavity, the blastocystic cavity , develops inside it. This change converts the morula into a blastocyst. Its centrally located cells, the inner cell mass or embryoblast , is the embryonic part of the embryo . Implantation . The process during which the blastocyst attaches to the endometrium , the mucous membrane or lining of uterus, and subsequently embeds in it. The preimplantation period of embryonic development is the time between fertilization and the beginning of implantation, a period of approximately 6 days.

10. Gestational Age .-the age the of the embryo or fetus from the presumed first day of the last normal menstrual period It is difficult to determine exactly when fertilization (conception) occurs because the process cannot be observed in vivo (within the living body). it is approximately 2 weeks longer than the fertilization age because the oocyte is not fertilized until approximately 2 weeks after the preceding menstruation Implantation- The process during which the blastocyst attaches to the endometrium , the mucous membrane or lining of uterus and embeds in it. preimplantation period of embryonic development is the time between fertilization and the beginning of implantation, a period of approximately 6 days. Gastrula (Gr. gaster , stomach)- a three-layered or trilaminar embryonic disc that forms in thethird week. During gastrulation (transformation of a blastocyst into a gastrulaThe three germ layers of the gastrula (ectoderm, mesoderm, and endoderm) subsequently differentiate into the tissues and organs of the embryo.

11. Neurula (Gr. neuron , nerve). The early embryo during the third and fourth weeks when the neural tube is developing from the neural plate (see Fig. 1-1). It is the first appearance of the nervous system and the next stage after the gastrula. Embryo (Gr. embryon ). The developing human during its early stages of development. The embryonic period extends to the end of the eighth week (56 days), by which time the beginnings of all major structures are present. The size of embryos is given as crown-rump length, which is measured from the vertex of the cranium (crown of head) to the rump (buttocks). Stages of Prenatal Development . Early embryonic development is described in stages because of the variable period it takes for embryos to develop certain morphologic characteristics Embryonic period- begins at fertilization and ends on day 56 (has stage 1-23). fetal period - begins on day 57 and ends when the fetus is completely outside the mother. Conceptus (L. conceptio , derivatives of zygote). The embryo and its adnexa (L., appendages or adjunct parts) or associated membranes (i.e., the products of conception ). includes all structures that develop from the zygote, both embryonic and extraembryonic. i.e the embryo as well as the embryonic part of the placenta and its associated membranes: amnion, chorionic (gestational) sac, and umbilical vesicle or yolk sac

12. Primordium (L. primus , first + ordior , to begin). The beginning or first discernible indication of an organ or structure. . Fetus (L., unborn offspring). After the embryonic period (8 weeks) and until birth, the developing human is called a fetus. During the fetal period (ninth week to birth), differentiation and growth of the tissues and organs formed during the embryonic period occur. Trimester . A period of three calendar months during a pregnancy. Obstetricians commonly divide the 9-month period of gestation into three trimesters. The most critical stages of development occur during the first trimester (13 weeks) when embryonic and early fetal development is occurring. Postnatal Period . The period occurring after birth. Explanations of frequently used developmental terms and periods follow. Infancy refers to the earliest period of extrauterine life, roughly the first year after birth . An infant aged 1 month or younger is called a newborn or neonate . Transition from intrauterine to extrauterine existence requires many critical changes, especially in the cardiovascular and respiratory systems.

13. Childhood is the period from approximately 13 months until puberty. The primary (deciduous) teeth continue to appear and are later replaced by the secondary (permanent) teeth. During early childhood, there is active ossification (formation of bone), but as the child becomes older, the rate of body growth slows down. Just before puberty, however, growth accelerates-the prepubertal growth spurt . Puberty occurs usually between the ages of 12 and 15 years in girls and 13 and 16 years in boys, during which secondary sexual characteristics develop and the capability of sexual reproduction is attained. The stages of pubertal development follow a consistent pattern and are defined by the appearance of secondary sexual characteristics (e.g., pubic hair development, breasts in females, and growth of external genitalia in males). Puberty ends in females with the first menstrual period or menarche , the beginning of the menstrual cycles or periods. Puberty ends in males when mature sperms are produced. Adolescence is the period from approximately 11 to 19 years of age, which is characterized by rapid physical and sexual maturation. It extends from the earliest signs of sexual maturity-puberty-until the attainment of adult physical, mental, and emotional maturity. The ability to reproduce is achieved during adolescence Adulthood (L. adultus , grown up), attainment of full growth and maturity, is generally reached between the ages of 18 and 21 years.

14. ABORTION Abortion (L. aboriri , to miscarry). A premature stoppage of development and expulsion of a conceptus from the uterus or expulsion of an embryo or fetus before it is viable-capable of living outside the uterus. Abortus is the products of an abortion (i.e., the embryo/fetus and its membranes). There are different types of abortion: Threatened abortion (bleeding with the possibility of abortion) is a complication in approximately 25% of clinically apparent pregnancies. Despite every effort to prevent an abortion, approximately half of these concepti ultimately abort. A spontaneous abortion is one that occurs naturally and is most common during the third week after fertilization. Approximately 15% of recognized pregnancies end in spontaneous abortion, usually during the first 12 weeks. A habitual abortion is the spontaneous expulsion of a dead or nonviable embryo or fetus in three or more consecutive pregnancies. An induced abortion is a birth that is medically induced before 20 weeks (i.e., before the fetus is viable). This type of abortion refers to the expulsion of an embryo or fetus induced intentionally by drugs or mechanical means A complete abortion is one in which all the products of conception are expelled from the uterus. A missed abortion is the retention of a conceptus in the uterus after death of the embryo or fetus. A miscarriage is the spontaneous abortion of a fetus and its membranes before the middle of the second trimester (approximately 135 days).

15. Gametogenesis 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. The sperm and oocyte , the male and female gametes, are highly specialized sex cells Gamete maturation is called spermatogenesis in males and oogenesis in females

16. Normal gametogenesis

17. Sexual Reproduction Sexual reproduction occurs when female and male gametes (oocyte and spermatozoon, respectively unite at fertilization. Primordial germ cells Gametes are direct descendants of primordial germ cells (from epiblast) , which are first observed in the wall of the yolk sac at week 4 of embryonic development and subsequently migrate into the future gonad region. Gametes are produced by gametogenesis (called oogenesis in the female and spermatogenesis in the male). Gametogenesis employs a specialized process of cell division, meiosis , which uniquely distributes chromosomes among gametes.

18. Chromosomes The X chromosome. A normal female somatic cell contains two X chromosomes (XX) . The female cell permanently inactivates one of the X chromosomes during week 1 of embryonic development. The choice of which X chromosome (maternal or paternal) is inactivated is random. The inactivated X chromosome (called the Barr body ) can be observed by light microscopy near the nuclear membrane. The Y chromosome. A normal male somatic cell contains one X chromosome and one Y chromosome (XY) . NB-Chromosome pairs 1–22 are autosomal ( nonsex ) pairs . Chromosome pair 23 consists of the sex chromosomes (XX for a female and XY for a male).

19. Meiosis is a specialized process of cell division that occurs only during the production of gametes within the female ovary or male testes. Meiosis consists of two divisions ( meiosis I and II ), which result in the formation of four gametes , each containing half the number of chromosomes (23 single chromosomes) and half the amount of DNA (1N) found in normal somatic cells (46 single chromosomes, 2N). A. Meiosis I. Events that occur during meiosis I include the following : 1. Synapsis: pairing of 46 homologous duplicated chromosomes. 2. Crossing over: exchange of large segments of DNA. 3. Alignment: alignment of 46 homologous duplicated chromosomes at the metaphase plate. 4. Disjunction: separation of 46 homologous duplicated chromosomes from each other; centromeres do not split . 5. Cell division: formation of two secondary gametocytes (23 duplicated chromosomes, 2N). B. Meiosis II. Events that occur during meiosis II include the following: 1. Synapsis: absent. 2. Crossing over: absent. 3. Alignment: alignment of 23 duplicated chromosomes at the metaphase plate. 4. Disjunction: separation of 23 duplicated chromosomes to form 23 single chromosomes; centromeres split. 5. Cell division: formation of four gametes (23 single chromosomes, 1N).

20. meiosis

21. A to D, Stages of prophase of the first meiotic division- The homologous chromosomes approach each other and pair; each member of the pair consists of two chromatids. D ,single crossover in one pair of chromosomes, resulting in the interchange of chromatid segments E, Metaphase - The two members of each pair become oriented on the meiotic spindle. F, Anaphase . G, Telophase- The chromosomes migrate to opposite poles. H, Distribution of parental chromosome pairs at the end of the first meiotic division. I to K, Second meiotic division - It is similar to mitosis except that the cells are haploid.

22. OOGENESIS Primordial germ cells (46, 2N) from the wall of the yolk sac arrive in the ovary at week 6 and differentiate into oogonia (46, 2N) , which populate the ovary through mitotic division. Oogonia enter meiosis I and undergo DNA replication to form primary oocytes (46, 4N) . All primary oocytes are formed by month 5 of fetal life . No oogonia are present at birth. Primary oocytes remain dormant in prophase of meiosis I from month 5 of fetal life until puberty. After puberty, 5 to 15 primary oocytes begin maturation with each ovarian cycle, with usually only 1 reaching full maturity in each cycle.

23. During the ovarian cycle and triggered by the luteinizing hormone (LH) surge, a primary oocyte completes meiosis I to form two daughter cells: the secondary oocyte (23, 2N) and the first polar body , which degenerates. The secondary oocyte promptly begins meiosis II but is arrested in metaphase of meiosis II about 3 hours before ovulation until fertilization occurs.

24. At fertilization, the secondary oocyte completes meiosis II to form a mature oocyte (23, 1N) and a second polar body . Approximate number of oocytes 1. Primary oocytes: At month 5 of fetal life, 7 million primary oocytes are present. At birth, 2 million are present (5 million have degenerated). At puberty, 40,000 are present (1.96 million more have degenerated). 2. Secondary oocytes: Twelve secondary oocytes are ovulated per year, up to 480 over the entire reproductive life of the woman (40 years × 12 secondary oocytes per year = 480). NB- This number (480) is obviously overly simplified since it is reduced in women who take birth control pills (which prevent ovulation), in women who become pregnant (ovulation stops during pregnancy), and in women who may have anovulatory cycles.

25. Spermatogenesis Spermatogenesis is classically divided into 3 phases: 1.Spermatocytogenesis 2.Meiosis 3.Spermiogenesis

26. Spermatocytogenesis 1. Primordial germ cells (46, 2N) from the wall of the yolk sac arrive in the testes at week 6 and remain dormant until puberty . At puberty, primordial germ cells differentiate into type A spermatogonia (46, 2N) . 2. Type A spermatogonia undergo mitosis to provide a continuous supply of stem cells throughout the reproductive life of the male. Some type A spermatogonia differentiate into type B spermatogonia (46, 2N) .

27. Meiosis 1. Type B spermatogonia enter meiosis I and undergo DNA replication to form primary spermatocytes (46, 4N) . 2. Primary spermatocytes complete meiosis I to form secondary spermatocytes (23, 2N) . 3. Secondary spermatocytes complete meiosis II to form four spermatids (23, 1N) .

28. 3.Spermiogenesis 1. Spermatids undergo a postmeiotic series of morphological changes to form sperm (23, 1N) . These changes include the (a) formation of the acrosome , (b) condensation of the nucleus, and (c) formation of head, neck, and tail. The total time of sperm formation (from spermatogonia to spermatozoa) is about 64 days . 2. Newly ejaculated sperm are incapable of fertilization until they undergo capacitation , which occurs in the female reproductive tract and involves the unmasking of sperm glycosyltransferases and the removal of adherent plasma proteins coating the surface of the sperm.

29. Clinical considerations 1.Offspring of older women 1. Prolonged dormancy of primary oocytes may be the reason for the high incidence of chromosomal abnormalities e.g trisomy 21 (Down syndrome)- maternal meiotic nondisjunction. increases with advanced age of the mother. Features; moderate mental retardation, microcephaly, microphthalmia, cataracts and glaucoma, flat nasal bridge, , protruding tongue, simian crease in the hand, increased nuchal skin folds, congenital heart defects..

30. 2.Offspring of older men An increased incidence of achondroplasia (a congenital skeletal anomaly characterized by retarded bone growth) and Marfan syndrome are associated with advanced paternal age.

31. Male infertility 1. Sperm number and motility: Infertile males produce less than 10 million sperm/mL of semen. Fertile males produce from 20 to more than 100 million sperm/mL of semen. Normally, up to 10% of sperm in an ejaculate may be grossly deformed (two heads or tw tails), but these sperm probably do not fertilize an oocyte because of their lack of motility . 2. Hypogonadotropic hypogonadism is a condition where the hypothalamus produces reduced levels of gonadotropin-releasing factor ( GnRF ), leading to reduced levels of follicle-stimulating hormone (FSH) and LH, and finally, reduced levels of testosterone. Kallmann syndrome is a genetic disorder characterized by hypogonadotropic hypogonadism and anosmia (loss of smell). 3. Drugs: cancer chemotherapy, anabolic steroids, cimetidine (histamine H 2 -receptor antagonist that inhibits stomach HCl production), spironolactone (a K + -sparing diuretic), phenytoin (an antiepileptic drug), sulfasalazine (a sulfa drug used to treat ulcerative colitis, Crohn disease, rheumatoid arthritis, and psoriatic arthritis), and nitrofurantoin (an antibiotic used to treat urinary tract infections). 4. Other factors: Klinefelter syndrome (XXY), seminoma, cryptochordism , varicocele , hydrocele, mumps, prostatitis, epididymitis, hypospadias, ductus deferens obstruction, and impotence.

32. Female infertility 1. Anovulation is the absence of ovulation in some women due to inadequate secretion of FSH and LH and is often treated with clomiphene citrate (a fertility drug) 2. Premature ovarian failure (primary ovarian insufficiency) is the loss of function of the ovaries before age 40, resulting in infertility. The cause is generally idiopathic, but cases have been attributed to autoimmune disorders, Turner syndrome, Fragile X syndrome, chemotherapy, or radiation treatment. 3. Pelvic inflammatory disease (PID) refers to the infection of the uterus, uterine tubes, and/ or ovaries leading to inflammation and scar formation. The cause is generally a sexually transmitted infection (STI), usually by Neisseria gonorrhea or Chlamydia trachomatis . 4. Polycystic ovarian syndrome is a complex female endocrine disorder defined by oligoovulation (infrequent, irregular ovulations), androgen excess, multiple ovarian cysts (by ultrasound). The cause is uncertain, but a strong genetic component exist. 5. Endometriosis is the appearance of foci of endometrial tissue in abnormal locations outside the uterus (e.g., ovary, uterine ligaments, pelvic peritoneum). The ectopic endometrial

33. THANK YOU

34. Week one of Human Development (Day 1-7) Fertilization occurs in the ampulla of the uterine tube Includes 3 phases; . Phase 1: Sperm penetration of corona radiata involves the action of both sperm and uterine tube mucosal enzymes. . Phase 2: Sperm binding and penetration of the zona pellucida Sperm binding occurs through the interaction of sperm glycosyltransferases and ZP3 receptors located on the zona pellucida . Sperm binding triggers the acrosome reaction , which entails the fusion of the outer acrosomal membrane and sperm cell membrane, resulting in the release of acrosomal enzymes. 2. Penetration of the zona pellucida requires acrosomal enzymes, specifically acrosin . Sperm contact with the cell membrane of a secondary oocyte triggers the cortical reaction , which entails the release o cortical granules (lysosomes) from the oocyte cytoplasm. This reaction changes the secondary oocyte cell membrane potential and inactivates sperm receptors on the zona pellucida . These changes are called the polyspermy block , which renders th secondary oocyte cell membrane impermeable to other sperm.

35. Phase 3: Fusion of sperm and oocyte cell membranes occurs with subsequent breakdown of both membranes at the fusion area. 1. The entire sperm (except the cell membrane) enters the cytoplasm of the secondary oocyte arrested in metaphase of meiosis II. The sperm nuclear contents and the centriole pair persist, but the sperm mitochondria and tail degenerate. The sperm nucleus becomes the male pronucleus . Since all sperm mitochondria degenerate, all mitochondria within the zygote are of maternal origin (i.e., all mitochondrial DNA is of maternal origin ). The oocyte loses its centriole pair during meiosis so that the establishment of a functional zygote depends upon the sperm centriole pair (a cardinal feature of human embryogenesis)

36. 2. The secondary oocyte completes meiosis II, forming a mature ovum and a second polar body. The nucleus of the mature ovum is now called the female pronucleus . 3. Male and female pronuclei fuse, forming a zygote (a new cell whose genotype is a combination of maternal and paternal chromosomes). 4. Syngamy is a term that describes the successful completion of fertilization, that is, the formation of a zygote. Syngamy occurs when the male and female pronuclei fuse and the cytoplasmic machinery for proper cell division exists. 5. The life span of a zygote is only a few hours because its existence terminates when the first cleavage division occurs.

37. Summary of the results of fertilization 1. Stimulates the penetrated oocyte to complete the second meiotic division. 2. Restores the normal diploid number of chromosomes (46) in the zygote. 3.Results in variation of the human species through mingling of maternal and paternal chromosomes. 4. Determines chromosomal sex of the embryo. 5. Causes metabolic activation of the ootid and initiates cleavage (cell division) of the zygote.

38. Cleavage and Blastocyst formation A. Cleavage is a series of mitotic divisions of the zygote Cleavage in humans is holoblastic , which means the cells divide completely through their cytoplasm. - Cleavage in humans is asymmetrical , which means the daughter cells are unequal in size (i.e., one cell gets more cytoplasm than the other) at least during the first few cell divisions. -Cleavage in humans is asynchronous , which means only one cell will divide at a time; generally, the largest daughter cell will divide next at least during the first few cell divisions. 2. The process of cleavage eventually forms a blastula consisting of cells called blastomeres .

39. 3. A cluster of blastomeres (16–32 blastomeres ) forms a morula . 4. Blastomeres are totipotent up to the eight-cell stage (i.e., each blastomere can form a complete embryo by itself ). Totipotency refers to a stem cell that can differentiate into every cell within the organism, including extraembryonic tissues.

40. B. Blastocyst formation involves fluid secreted within the morula that forms the blastocyst cavity . The conceptus is now called a blastocyst . 1. The inner cell mass of the blastocyst is called the embryoblast (becomes the embryo). The embryoblast cells are pluripotent . Pluripotency refers to a stem cell that can differentiate into ectoderm, mesoderm, and endoderm. 2. The outer cell mass of the blastocyst is called the trophoblast (becomes the fetal portion of the placenta) C. Zona pellucida degeneration occurs by day 4 after conception. The zona pellucida must degenerate for implantation to occur.

41. Clinical correlation Ectopic tubal pregnancy (ETP) 1. ETP occurs when the blastocyst implants within the uterine tube due to delayed transport . Testicular teratocarcinoma (TTC TTC is a germ cell neoplasm. In its early histologic stages, a TTC resembles a blastocyst with three primary germ layers and may be loosely referred to as “male pregnancy.” 2. TTC contains well-differentiated cells and structures from each of the three primary germ layers: for example, colon glandular tissue (endoderm), cartilage (mesoderm), and squamous epithelium (ectoderm).

42. Second week of Embryonic Development (Day 8-14) During this time period, the embryoblast differentiates into two distinct cellular layers: the dorsal epiblast layer (columnar cells) and the ventral hypoblast layer (cuboidal cells). The epiblast and hypoblast together form a flat, ovoid-shaped disk known as the bilaminar embryonic disk. Within the epiblast , clefts begin to develop and eventually coalesce to form the amniotic cavity. Hypoblast cells begin to migrate and line the inner surface of the cytotrophoblast , forming the exocoelomic membrane, which delimits a space called the exocoelomic cavity (or primitive yolk sac ). This space is later called the definitive yolk sac when a portion of the exocoelomic cavity is pinched off as an exocoelomic cyst. At the future site of the mouth, hypoblast cells become columnar shaped and fuse with epiblast cells to form a circular, midline thickening called the prochordal plate.

43. Further development of the trophoblast Syncytiotrophoblast . The syncytiotrophoblast is the outer multinucleated zone of the trophoblast where no mitosis occurs (i.e., it arises from the cytotrophoblast ). Lacunae form decidual cells- filled with glycogen and lipids and also supply nutrients to the embryoblast - lacunar network- uteroplacental circulation Cytotrophoblast . The cytotrophoblast is mitotically active as new cytotrophoblastic cells migrate into the syncytiotrophoblast , thereby fueling its growth.

44. With development of blood vessels, the stalk becomes the umbilical cord. The syncytiotrophoblast is responsible for production hormone human chorionic gonadotropin ( hCG ) By the end of the second week, quantities of this hormone are sufficient to be detected by radioimmunoassays , which serve as the basis for pregnancy testing.

45. Dev of extraembryonic mesoderm The extraembryonic mesoderm develops from the epiblast and consists of loosely arranged cells that fill the space between the exocoelomic membrane and the cytotrophoblast Large spaces develop in the extraembryonic mesoderm and coalesce to form the extraembryonic coelom. The extraembryonic coelom divides the extraembryonic mesoderm into the extraembryonic somatic mesoderm and extraembryonic visceral mesoderm.

46. Summary-week of Two’s Epiblast and Hypoblast Amniotic cavity and Exocoelomic cavity(yolk sac) Syncytiotrophoblast and Cytotrophoblast Extraembryonic somatic mesoderm and Extraembryonic visceral mesoderm .

47. Third Week of Embryonic Development(Week of Three’s) GASTRULATION Gastrulation is the process that establishes the three definitive germ layers of the embryo ( ectoderm, intraembryonic mesoderm, and endoderm ), forming a trilaminar embryonic disk by day 21 of development. These three germ layers give rise to all the tissues and organs of the adult. Gastrulation is first indicated by the formation of the primitive streak, caused by a proliferation of epiblast cells. The primitive streak consists of the primitive groove, primitive node, and primitive pit. Located caudal to the primitive streak is the future site of the anus, known as the cloacal membrane, where epiblast and hypoblast cells are fused.

48. Fate Map of cells Established During Gastrulation Cells of the epiblast that migrate and ingress through the primitive streak have been mapped and their ultimate fates determined as follows:- 1. Cells that ingress through the cranial region of the node become notochord; 2. Cells migrating at the lateral edges of the node and from the cranial end of the streak become paraxialmesoderm ; 3. those migrating through the mid-streak region become intermediate mesoderm; 4. those migrating through the more caudal part of the streak form lateral plate mesoderm ; 5. cells migrating caudal-most part of the streak contribute to extraembryonic mesoderm (the other source of this tissue is the primitive yolk sac [hypoblast]

49. Changes involving intraembryonic mesoderm Paraxial mesoderm is a thick plate of mesoderm located on each side of the midline. Paraxial mesoderm becomes organized into segments known as somitomeres and somites which form in a craniocaudal sequence. Sclerotome forms the cartilage and bone components of the vertebral column. Myotome forms epimeric and hypomeric muscles. Dermatome forms dermis and subcutaneous area of skin.

50. 2.Intermediate mesoderm is a longitudinal dorsal ridge of mesoderm located between the paraxial mesoderm and lateral mesoderm. This ridge forms the urogenital ridge, which is involved in the formation of the future kidneys and gonads. 3. Lateral mesoderm is a thin plate of mesoderm located along the lateral sides of the embryo. Large spaces develop in the lateral mesoderm and coalesce to from the intraembryonic coelom. The intraembryonic coelom divides the lateral mesoderm into two layers: a. Intraembryonic somatic mesoderm (also called somatopleure ) b. Intraembryonic visceral mesoderm (also called visceropleure or splanchnopleure )

51. Derivatives of the Ectoderm Epidermis, hair, nails, sweat and sebaceous glands Utricle, semicircular ducts, vestibular ganglion of CN VIII Saccule , cochlear duct (organ of Corti ), spiral ganglion of CN VIII Olfactory placode , CN I Ameloblasts (enamel of teeth) Adenohypophysis Lens of eye Anterior epithelium of cornea Acinar cells of parotid gland Acinar cells of mammary gland Epithelial lining of: Lower anal canal Distal part of male urethra External auditory meatus

52. Derivatives of the Mesoderm Muscle (smooth, cardiac, skeletal) Extraocular muscles, ciliary muscle of eye, iris stroma , ciliary body stroma Substantia propria of cornea, corneal endothelium, sclera, choroid Muscles of tongue (occipital somites ) Pharyngeal arch muscles Laryngeal cartilages Connective tissue Dermis and subcutaneous layer of skin Bone and cartilage Dura mater Endothelium of blood and lymph vessels Red blood cells, white blood cells, microglia, and Kupffer cells Spleen Kidney Adrenal cortex Testes, epididymis, ductus deferens, seminal vesicle, ejaculatory duct Ovary, uterus, uterine tubes, superior 1/3 of vagina

53. Derivatives of the Endoderm Hepatocytes Principal and oxyphil cells of parathyroid Thyroid follicular cells thymus Epithelial reticular cells of thymus Acinar and islet cells of pancreas Acinar cells of submandibular and sublingual glands Epithelial lining of: Gastrointestinal tract Trachea, bronchii , lungs Biliary apparatus Urinary bladder, female urethra, most of male urethra Inferior 2/3 of vagina Auditory tube, middle ear cavity Crypts of palatine tonsils

54. Derivatives of the Neural crest cells Cranial neural crest cells: Pharyngeal arch skeletal and connective tissue components Bones of neurocranium Pia and arachnoid Parafollicular (C) cells of thyroid Aorticopulmonary septum Odontoblasts (dentin of teeth) Sensory ganglia of CN V, CN VII, CN IX, CN X Ciliary (CN III), pterygopalatine (CN VII), submandibular (CN VII), and otic (CN IX) parasympathetic Ganglia Trunk neural crest cells: Melanocytes Schwann cells Chromaffin cells of adrenal medulla Dorsal root ganglia Sympathetic chain ganglia Prevertebral sympathetic ganglia Enteric parasympathetic ganglia of the n gut (Meissner and Auerbach; CN X ) Abdominal/pelvic cavity parasympathetic ganglia

55. NOTOCHORD Notochord is a solid cylinder of mesoderm extending in the midline of the trilaminar embryonic disk from the primitive node to the prochordal plate. Functions a. It induces the overlying ectoderm to differentiate into neuroectoderm to form the neural plate. b. It induces the formation of the vertebral body of each of the vertebrae. c. It forms the nucleus pulposus of each intervertebral disk.

56. Teratogenesis associated with gastrulation Poor fatemap of cells during gastrulation – may be due to alcohol intake, diabetes,serotonin (5HT) e.t.c causing holoprocencephaly , caudal dysgenesis, situs inversus ( commonly present with kartagener’s syndrome , dextrocardia ) Sacrococcygeal teratoma

57. FOURTH WEEK OF EMBRYONIC DEVELOPMENT Neurulation and Embryonic folding

58. NEURILATION It is the formation of the neural plate and neural tube begins (22-23 days) in the region of the fourth to sixth pairs of somites

59. The nervous system develops from the neural plate (a thickened area of embryonic ectoderm) induced by the notochord The neural tube differentiates into the CNS, consisting of the brain and spinal cord. The neural crest gives rise to cells (Neural crest cells) that form most of the PNS and ANS, consisting of cranial, spinal, and autonomic ganglia, and many other structures.

60. the cranial two thirds of the neural plate and tube represent the future brain, and the caudal one third of the neural plate and tube represents the future spinal cord. Fusion of the neural folds and formation of the neural tube proceeds in cranial and caudal directions until only small areas of the tube remain open at both ends( rostral and caudal neuropore) The neural canal forms the ventricular system of the brain and the central canal of the spinal cord.

61. FOLDING OF THE EMBRYO A significant event in the establishment of body form is folding of the flat trilaminar embryonic disc into a somewhat cylindrical embryo Folding occurs in both the median and horizontal planes and results from rapid growth of the embryo

62. Folding of the Embryo in the Median Plane Folding of the ends of the embryo ventrally This produces head and tail folds that result in the cranial and caudal regions moving ventrally as the embryo elongates cranially and caudally

63. Head Fold By the beginning of the fourth week, the neural folds in the cranial region have thickened to form the primordium of the brain. Later, the developing forebrain grows cranially beyond the oropharyngeal membrane and overhangs the developing heart. The septum transversum (transverse septum), primordial heart, pericardial coelom, and oropharyngeal membrane move onto the ventral surface of the embryo

64. Tail Fold Folding of the caudal end of the embryo results primarily from growth of the distal part of the neural tube-the primordium of the spinal cord As the embryo grows, the caudal eminence (tail region) projects over the cloacal membrane (future site of anus).

65. Folding of the Embryo in the Horizontal Plane Folding of the sides of the embryo produces right and left lateral folds . Lateral folding is produced by the rapidly growing spinal cord and somites . The primordia of the ventrolateral wall fold toward the median plane, rolling the edges of the embryonic disc ventrally and forming a roughly cylindrical embryo. As the abdominal walls form, part of the endoderm germ layer is incorporated into the embryo as the midgut (primordium of small intestine. Initially, there is a wide connection between the midgut and umbilical vesicle. After lateral folding, the connection is reduced to an omphaloenteric duct . The region of attachment of the amnion to the ventral surface of the embryo is also reduced to a relatively narrow umbilical region

66. Lateral folding With lateral folding mesoderm is recruited to gut wall Mesodermal layer of the gut tube is called splanchnic (visceral) mesoderm - derived from lateral plate mesoderm

67. FORMATION OF THE BODY CAVITIES The intraembryonic coelom becomes the embryonic body cavity which is divided into three well-defined cavities during the fourth week 1. A pericardial cavity 2.Two pericardioperitoneal canals 3.A peritoneal cavity

68. These body cavities have a parietal wall lined by mesothelium- future parietal layer from somatic mesoderm visceral wall covered by mesothelium- future visceral layer derived from splanchnic mesoderm The peritoneal cavity (the major part of intraembryonic coelom) is connected with the extraembryonic coelom at the umbilicus The peritoneal cavity loses its connection with the extraembryonic coelom during the 10th week as the intestines return to the abdomen from the umbilical cord

69. During formation of the head fold , the heart and pericardial cavity are relocated ventrocaudally , anterior to the foregut NB : After embryonic folding, the caudal part of the foregut , the midgut , and the hindgut are suspended in the peritoneal cavity from the dorsal abdominal wall by the dorsal mesentery

70. Division of the embryonic body cavity Begin by formation of ; Cranial and caudal ridges that form pleuropericardial and pleuroperitonial folds respectively Pleuropericardial folds enlarge forming pleuropericardial membranes that separate pericardial from the pleural cavity pleuroperitonial folds enlarge forming pleuroperitoneal membranes that separate the pleural cavity from peritoneal cavity

71. Mesenteries A mesentery is a double layer of peritoneum that begins as an extension of the visceral peritoneum covering an organ It connects the organ to the body wall and conveys vessels and nerves to it. divide the peritoneal cavity into right and left halves The ventral mesentery soon disappears except where it is attached to the caudal part of the foregut The peritoneal cavity then becomes a continuous space The arteries supplying the primordial gut pass between the layers of the dorsal mesentery

72. FETAL MEMBRANES AND PLACENTA Structure of the placenta Beginning of the fourth month, the placenta has two components: (1 ) Fetal portion , formed by the chorion frondosum and (2) Maternal portion , formed by the decidua basalis . On the fetal side, the placenta is bordered by the chorionic plate; on its maternal side, it is bordered by the decidua basalis Between the chorionic and decidual plates are the intervillous spaces , which are filled with maternal blood. They are derived from lacunae in the syncytiotrophoblast and are lined with syncytium of fetal origin During the 4 th and 5 th months, the decidua forms a number of decidual septa, which project into intervillous spaces but do not reach the chorionic plate dividing placenta into cotyledons . These septa have a core of maternal tissue, but their surface is covered by a layer of syncytial cells, so that at all times, a syncytial layer separates maternal blood in intervillous lakes from fetal tissue of the villi

73. Placenta in the second half of the pregnancy

74. Functions of the placenta Exchange of gases Exchange of nutrients and electrolytes Transmission of maternal antibodies e.g immunoglobulin G Hormone production e.g progesterone, estriol,hcG , somatomammotropin

75. Development of the placenta Primary villi begin to form in the 2 nd week from the cytotrophoblast Beginning of the 2nd month , trophoblast is characterized by secondary and tertiary villi Stem (anchoring) villi extend from the mesoderm in the chorionic plate to the cytotrophoblast shell Maternal blood is delivered to the placenta by spiral arteries in the uterus. Erosion of these maternal vessels to release blood into intervillous spaces is accomplished by endovascular invasion by cytotrophoblast cells released from the ends of anchoring villi numerous small extensions grow out from existing stem villi and extend as free (branch) villi into the surrounding lacunar or intervillous spaces. beginning of the 4 th month , cytotrophoblastic cells and some connective tissue cells disappear . The syncytium and endothelial wall of the blood vessels are then the only layers that separate the maternal and fetal circulations Large pieces of syncytium may break off and drop into the intervillous blood lakes ( syncytial knots)

76. The placental membrane (barrier)

77. Chorion Frondosum and decidua basalis Chorion frondosum also known as bushy chorion is the area on the embryonic pole where the villi grow and expand Chorion leave is the smooth part of the chorion in the abembryonic pole where the villi degenerate during the third month The amnion and the chorion fuse to form amniochorionic membrane

78. Clinical correlates Preeclampsia – characterized by hypertension and proteinuria due to reduced organ perfusion Eclampsia Hemolytic disease of the fetus and newborn Fetal hydrops – edema and effusion into body cavities

79. Amnion and umbilical cord Primitive umbilical ring ( amnioectodermal junction) contains the following by 5 th week of development 1. Connecting stalk (contain allantois and umbilical vessels) 2. Yolk stalk (vitelline duct) 3. Canal connecting intraembryonic and extraembryonic cavity With further development, the amniotic cavity enlarges rapidly at the expense of the chorionic cavity So the amnion begins to envelop the connecting and yolk sac stalks, crowding them together and giving rise to the primitive umbilical cord

80. Structures passing through primitive umbilical ring-5 th week

81. Amniotic fluid Clear watery fluid that fill the amniotic cavity produced by the amniotic cells and the maternal blood Amniotic fluid increases from ; 30ml at 10 weeks, 450ml at 20 weeks, 800-1000 at 37 weeks

82. Clinical correlates Placental abnormalities Placenta accreta Placenta percreta Placenta Previa 2. Preeclampsia – characterized by hypertension and proteinuria due to reduced organ perfusion Eclampsia 2. Hemolytic disease of the fetus and newborn Fetal hydrops – edema and effusion into body cavities 3. Umbilical cord abnormalities Too long or too short cord (normal 50-60cm) One umbilical artery

83. Clinical correlates cont … 4. Amniotic bands 5. Amniotic fluid Polyhydramnios (1500-2000 mls )- may be due to cns and git malformations, diabetes,e.t.c Oligohydramnios (<400 mls )- may reslt from renal agenesis leading to lung hypoplasia, club foot 6. Premature rupture of membranes (PROM) - rupture of membranes before uterine contractions begin, b4 37 complete weeks

84. Fetal Hydrops, Limb constriction, digit amputation

85. Fetal membranes in twins Dizygotic (fraternal twins) – occur when two oocytes are fertilized by different spermatozoa Monozygotic twins (identical twins)- single fertilized ovum, splitting of the zygote

86. Dizygotic twins

87. Fetal membranes in monozygotic

88. Abnormalities associated with twins Vanishing twin- death of one fetus due to resorption or formation of fetus papyraceus , twin to twin transfusion syndrome Conjoined twins

89. Fetus papyraceus , twin to twin transfusion syndrome

90. Conjoined twins

91. Parturition(childbirth) It is a process by which the fetus, placenta and the fetal membranes are expelled from the mothers reproductive tract. Labor- is a sequence of involuntary uterine contractions that result in dilatation of the cervix and expulsion of the fetus and placeta from the uterus 3 stages of labor: Stage 1(Dilatation): Effacement (thinning and shortening) and dilatation of the cervix Stage 2(Expulsion): Delivery of the fetus Stage 3 (Placental stage): Delivery of the placenta and the fetal membranes