General Embryology PDF

# General Embryology ## Contents | No. | Topic | Page | |---|---|---| | 1 | Gametogenesis | 1 | | 2 | Ovarian cycle | 6 | | 3 | Fertilization | 8 | | 4 | Cleavage | 11 | | 5 | Implantation | 13 | | 6 | Formation of Germ Layers | 15 | | 7 | Formation of Trilaminar Germ Disc | 19 | | 8 | Derivatives...

# General Embryology ## Contents | No. | Topic | Page | |---|---|---| | 1 | Gametogenesis | 1 | | 2 | Ovarian cycle | 6 | | 3 | Fertilization | 8 | | 4 | Cleavage | 11 | | 5 | Implantation | 13 | | 6 | Formation of Germ Layers | 15 | | 7 | Formation of Trilaminar Germ Disc | 19 | | 8 | Derivatives of Germ Layers | 26 | | 9 | Fetal Membranes | 28 | | 10 | Placenta | 34 | | 11 | Fetal Period | 39 | | 12 | Multiple Pregnancy | 43 | | 13 | Teratogenesis | 48 | ## Gametogenesis Gametogenesis is the process by which male and female germ cells undergo a number of chromosomal and morphological changes in preparation for fertilization. ### Chromosomal Changes - To reduce number of chromosomes from diploid number (46) to haploid number (23), observed in gamete which is accomplished by meiotic divisions. ### Morphological Changes - **Male germ cells**: Initially large and round, lose all of its cytoplasm and develops into a head, neck and tail. - **Female germ cells**: Gradually becomes larger as a result of an increase in the amount of cytoplasm. - **At maturity**: the oocyte has a diameter of about 120 μ. ### Spermatogenesis - In male, primordial germ cells remain dominant in the seminiferous tubules of testes until puberty. - At puberty, primordial germ cells differentiate into spermatogonia. - After several mitotic divisions, spermatogonia grow and undergo gradual changes that transform them into primary spermatocytes. - Each primary spermatocyte undergoes 1st meiotic division to form 2 haploid secondary spermatocytes. - Secondary spermatocytes undergo 2nd meiotic division to form 4 haploid spermatids. - Spermatids are gradually transformed into 4 mature sperms or spermatozoa by spermiogenesis. - It includes: - Formation of acrosomal cap - Condensation of the nucleus to form head - Formation of the neck, middle piece and tail, and - Shedding of most of the cytoplasm. **Fig.1. Process of spermatogenesis (Sadler & Langman, 2019)** **Fig.2. Important stages in spermiogenesis (Sadler & Langman, 2019)** - *Entire process of spermatogenesis and spermiogenesis take about 74 days.* - *Spermatozoa are transported passively from the seminiferous tubules to the epididymis where they are stored and become functionally mature.* ### Morphological Characteristics of Normal Human Spermatozoa | Characteristic | Measurements | |---|---| | Length | 65μ | | Number | 100 million per ml of semen | | Motility at emission | more than 80% | | Survival in female genital tract | Several days (72 hours) | | Amount of semen per ejaculate | 2-3 ml | **Fig.3. Various types of abnormal spermatozoa (Sadler & Langman, 2019)** **Applied Anatomy** 1. **Abnormal spermatozoa**: Spermatozoa with abnormally large/small heads, 2 or more tails or 2 heads. 2. **Chromosomal abnormalities**: Structural and numerical abnormalities during cell division. ## Oogenesis - In the female, primordial germ cells differentiate into oogonia as soon as they reach indifferent gonad. - Although it begins before birth, it is completed after puberty. ### During intrauterine life - Oogonia proliferate to form primary oocyte by mitotic division. - Immediately after their formation, it enters first meiotic division. - By 7th month, all primary oocytes entered 1st meiotic division and most of them are surrounded by flat follicular cells (Primordial follicle) which secrete the oocyte maturation inhibitors (OMI). - The oocyte does not finish their 1st meiotic divisions but remain in diplotene stage until puberty. - Thus, no primary oocytes are formed after birth in females. ### At puberty, - A number of primodial follicles begin to mature with each ovarian cycle. - The primary oocytes (still in diplotene stage) begin to increase in size. - Surrounding follicular cells change flat to cuboidal and proliferate to form stratified layers of granulosa cells (Primary follicle). - Both granulosa cells and oocyte secrete a layer of glycoprotein coat forming zona pellucida. - Cells of theca folliculi which surround the primary follicle organized into inner layer of theca interna and outer layer of theca externa containing fibroblast-like cells. Theca interna produce oestrogen. - Fluid filled spaces appear between granulosa cells and when spaces coalesce; antrum is formed and is termed as Secondary follicle. **Fig.4. Process of oogenesis (Sadler & Langman, 2019)** - *Initially, antrum is cresent shaped, but greatly enlarges. Granulosa cells surrounding the oocyte remain intact and form cumulus oophorus (Teniary vesicular or Graafian follicle).* **Fig.5. Various stages of follicle (Sadler & Langman, 2019)** **Fig.6. (A) Vesicular stage follicle (B) Graafian follicle (Sadler & Langman, 2019)** - *With each ovarian cycle, a number of follicles (5-15) begin to develop, but only one reach full maturity, others degenerate and become atretic.* - *As soon as the follicle is mature, primary oocyte resumes 1st meiotic divisions* - *After completion of 1st meiotic division, it leads to 2 daughter cells of unequal size. Secondary oocyte and 1st polar body (each 23 double stranded chromosome).* - *Secondary oocyte cells enter 2nd meiotic division.* - *Ovulation occurs and secondary oocyte is shed from the ovary.* - *2nd maturation division is completed only if the oocyte is fertilized.* - *Fertilized oocyte retains its most cytoplasm and soon degenerates, 24 hr after ovulation.* - *There are about 700,000 to 2 million primary oocytes in the ovaries of newborn female infant, but many regress during childhood.* - *Only 40,000 are present by the beginning of puberty.* - *Of these fewer than 500 will be ovulated.* ## Applied Anatomy - **Morphological anomalies**: Abnormal ovum - Primordial follicle with 2 oocytes - Trinucleated oocyte - **Chromosomal anomalies**: Structural and numerical anomalies may originate during meiotic divisions and occasionally during mitotic divisions **Fig. 7. (A) Primordial follicle with two oocytes (B) Primordial follicle with trinucleated oocyte (Sadler & Langman, 2019)** ## Ovarian Cycle - Ovarian cycle is controlled by hypothalamus by producing GnRH. - It acts on the anterior pituitary gland to secrete gonadotrophins FSH and LH. - FSH promotes growth of several ovarian follicles (5-15) but usually only one forms a mature follicle. - Others degenerate and become atretic and are replaced by connective tissue forming corpus atreticum. - Follicular and theca cells produce oestrogen which stimulates pituitary gland to secrete LH. - LH causes follicle maturation and induces shedding of oocyte. **Fig.8. Role of hypothalamus and pituitary gland regulating the ovarian cycle (Sadler & Langman, 2019)** ### Ovulation - Ovulation is rupture of Graafian follicle and expulsion of secondary oocyte together with zona pellucida and surrounding cumulus oophorous cells. - It appears approximately 14 ±1 day before the onset of next menstruation. ### Corpus luteum - Following ovulation, granulosa cells remaining in wall of ruptured follicle together with the cells from theca interna develop into yellowish pigment and change into luteal cells forming corpus luteum under the influence of LH. - They secrete progesterone. - It reaches maximum development 9 days after ovulation. ### Corpus albican - If fertilization fails to occur, corpus luteum degenerates and forms a mass of fibrotic scar known as corpus albican. ### Corpus luteum of pregnancy (Corpus Gravidarum) - If fertilization occurs, corpus luteum persists for 4 months. It produces progesterone. **Applied Anatomy** 1. **Symptoms of ovulation**: Slight bleeding into the peritoneal cavity causing sudden constant inferolateral pain in the abdomen (Mittelschemerz pain) - Slight rise in basal body temperature 2. **Ovulation can be inhibited by contraceptive methods containing progesterone and small amount of estrogen.** 3. **Ovulation can be artificially stimulated by administration of gonadotrophins or ovulating drugs such as clomiphene citrate** **Fig.9. Ovulation (Sadler & Langman, 2019)** ## Fertilization - It is the process by which male and female gametes fuse to form a single cell called zygote. ### Site: - Ampullary part of uterine tube ### Sperm transport - Spermatozoa pass rapidly from vagina into the uterus and uterine tube by flagella activity and muscular contraction of uterus and uterine tube. - In the tube, isthmus serves as sperm reservoir and movement to ampulla is a synchronized process. ### Oocyte transport - Secondary oocyte surrounded by zona pellucida and cumulus oophorous is expelled at ovulation. - It is carried into uterine tube by sweeping movement of fimbriae and motion of cilia on the epithelial lining and is pushed towards the uterine cavity by muscular contraction of tube. ### Maturation of sperm - Sperm arrived into the female genital tract are not capable of fertilizing oocyte. - They undergo: - Capacitation- removal of glycoprotein coat that overlies acrosomal region of spermatozoa. - Acrosome reaction - release of acrosomal enzymes to penetrate zona pellucida. ### Viability of Gametes - Oocyte is viable about 24 hours after ovulation. - Spermatozoa are viable for several days. ### Phase of fertilization - **Phase 1 - Penetration of corona radiata**: Capacitated sperm passes freely through corona radiata by the action of hyaluronidase which is released from the acrosome of the sperms. - **Phase 2 - Penetration of zona pellucida**: By the action of acrosin. - **Phase 3 - Fusion of oocyte and sperm cell membranes**: When a spermatozoon has entered the oocyte, the 2 plasma membranes fuse and egg responds in 3 different ways. - Cortical and zona reaction - oocyte membrane and zona pellucida impenetrable to sperms to prevent the polyspermy - Resumption of 2nd meiotic division - Metabolic activation of egg for early embryogenesis. **Fig.10. Three phases of fertilization (Sadler & Langman, 2019)** ### Results of fertilization 1. Completion of 2nd meiotic division of female gamete 2. Formation of zygote 3. Restoration of diploid number of chromosomes 4. Determination of sex of embryo 5. Initiation of cleavage ### Abnormal Fertilization 1. **Parthenogenesis**: Oocyte is activated without sperm penetration and development may begin 2. **Superfecundation**: - It follows polyovulation. - 2 oocytes fertilized by 2 spermatozoa from 2 different males (seen in various mammals, not usual in human) 3. **Superfetation**: Ovulation and fertilization occurs during pregnancy 4. **Dispermy and Triploidy**: 2 sperms may penetrate 1 oocyte in fertilization ### Applied Anatomy - **Contraceptive methods**: Barrier (male and female condom) - Contraceptive pills (combination of oestrogen and progesterone analogue progestin) which inhibit ovulation but permit menstruation. - Depo-Provera (injected IM or implanted subdermally) which inhibit ovulation, - Intrauterine contraceptive device (IUCD) - Tube ligation in female or vasectomy in male ## Cleavage - A single cell zygote divides into two cell stage by mitotic division. - The two cell stage zygote undergoes a series of mitotic divisions, resulting in increase in number of cells (blastomeres) - Cleavage begins about 30 hours after fertilization - During cleavage the zygote is within the zona pellucida - 16 cells stage zygote (morula or mulberry) is formed about 3 days after fertilization - About 4 days after fertilization, fluid filled space appears inside the morula is called blastocyst cavity or blastocele - As fluid increase in the blastocyst cavity, it separates the blastomere into two parts: - Outer cell mass - trophoblast - Inner cell mass - embryoblast - At this stage, the conceptus is called blastocyst - About 6 days after fertilization, embryonic pole of blastocyst attaches to endometrium of uterus. **Fig.11. Events during the first week of human development (Sadler & Langman, 2019)** - *The two cell stage zygote undergoes a series of mitotic divisions, resulting in increase in number of cells (blastomeres)* **Fig.12. Human blastocyst with embryoblast and trophoblast: Blastocyst penetration the uterine mucosa (Sadler & Langman, 2019)** ## Implantation - Implantation is burrowing and embedding of early blastocyst into the deep layers of uterine endometrium by the end of the 1st week of development. ### Site of implantation - It occurs along posterior or anterior wall of body of uterus near the fundus. ### Uterus at the time of implantation - Cyclical changes in the endometrium occur during reproductive age i.e; from puberty (11-13 year) to menopause (40-50 year) is known as menstrual cycle or uterine cycle. - It occurs approximately 28 days. ### During menstrual cycle, uterine endometrium pass through 3 stages - follicular or proliferative phase, - secretory or progestational phase and - menstrual phase. - *At the time of implantation, mucosa of uterus is in secretory phase.* - *(If the oocyte is not fertilized, menstrual phase begins. Menstrual blood flow consists of blood, partially disintegrated epithelium and stroma and secretions of endometrial glands.)* ### Abnormal sites of implantation 1. **Outside the uterus (Extrauterine or ectopic pregnancy)** - In abdominal cavity especially in recto-uterine pouch - In the ampullary region of tube - Tubal implantation (most dangerous) - Interstitial implantation in the narrow portion of tube - Ovarian implantation 2. **Within the uterus, close to internal os of cervix, resulting in placenta previa** ### Applied anatomy 1. **Immunosuppressant protein** - early pregnancy factor (EPF) is secreted by trophoblast and appears in maternal serum within 24-48 hour after fertilization. EPF forms basis of pregnancy test during 1st 10 days of development. 2. **High level of chorionic gonadotrophic hormones** in the urine (by the end of 2nd week) forms the basis for diagnostic test for pregnancy 3. **Inhibition of implantation** - post conception administration of high doses of hormone for several days to prevent implantation of blastocyst 4. **Pre-implantation diagnosis of genetic disorders** using micromanipulation and DNA application 5. **Tubal pregnancy detection** by endovaginal or intravaginal ultrasound **Fig.13. Abnormal implantation sites of the blastocyst (Sadler & Langman, 2019)** ## Stages of Development 1. **Germinal period** - from the time of fertilization to the formation of germ layers, i.e. end of 2nd week. 2. **Embryonic Period** - third to eight week of development, each of 3 germ layers gives rise to number of specific tissues and organs. 3. **Fetal period**- 3rd month to the end of intrauterine life. ### Date of delivery - The average times is 280 days from the beginning of the last menstrual period (LMP). - 38 weeks (266 days) - true age of the fetus - duration of pregnancy - gestation period - 7th month. ### Viable age of the foetus - A foetus may be born prematurely at 7 month, but it is capable of independent existence due to the establishment of pulmonary respiration. ## Formation of Germ Layers ### Formation of Bilaminar Germ Disc - **8th Day**: - **Blastocyst**: - Is partially embedded in the endometrial stroma - Endometrial stroma adjacent to implantation site undergoes decidua reaction which undergoes edematous, highly vascular & tortuous glands - **Trophoblast**: - Inner cytotrophoblast (mono-nucleated cell) - Outer syncytiotrophoblast (multi-nucleated cells) which erode maternal tissue - **Embryoblast**: - Hypoblast - Small cuboidal cells adjacent to blastocyst cavity - Epiblast - High columnar cells (close to inner side of cytotrophoblast) - Hypoblast and epiblast layers form bilaminar germ disc. - Formation of amniotic cavity within the epiblast - Amnioblast (epiblast cells adjacent to cytotrophoblast) **Fig.14. A 7.5 day human blastocyst (Sadler & Langman, 2019)** - **9th Day**: - **Blastocyst**: - Is deeply embedded in endometrium - Defect is closed by fibrin coagulum (blood clot) - **Trophoblast**: - Syncytiotrophoblast - formation of lacunae at embryonic pole - **Embryoblast**: - Heuser's membrane (exocoelomic membrane) from hypoblast that lines inner surface of cytotrophoblast to form the primary yolk sac or primitive yolk sac or exocoelomic membrane. **Fig.15. A 9-day human blastocyst (Sadler & Langman, 2019)** - **11th to 12th Day**: - **Blastocyst**: - Is completely embedded - Surface epithelium almost entirely covers the original defect in uterine wall - Decidual reaction spread throughout endometrium - **Trophoblast**: - Syncytiotrophoblast penetrate the stroma and is continuous with maternal sinusoids establishing utero-placental circulation - **Embryoblast**: - New cell population derived from yolk sac between inner surface of cytotrophoblast & outer surface of exocoelomic cavity known as extra-embryonic mesoderm. - Large cavities in E.E.M become confluence & form chorionic cavity or extra-embryonic coelom. - E.E.M lining the cytotrophoblast & amnion formed extra-embryonic somatopleuric mesoderm. - E.E.M lining the yolk sac formed extra-embryonic splanchnopleuric mesoderm **Fig.16. A 12-day human blastocyst (Sadler & Langman, 2019)** - **13th Day**: - **Blastocyst**: - Surface defect- healed - Bleeding may occur at implantation site as a result of increased blood flow into lacunar spaces (Implantation bleeding). - It may be confused with menstrual bleeding. - It can cause inaccuracy in determining expected delivery date (EDD) - **Trophoblast**: - Cytotrophoblast - penetrate into syncytiotrophoblast and forming the primary villi - **Embryoblast**: - Hypoblast produces additional cells (inside the Heuser's membrane) that migrate the inside of the exocoelomic membrane forming definitive yolk sac or secondary yolk sac. - Pinched off portion of exocoelomic cavity form the exocoelomic cyst in chorionic cavity. - E.E.M lining inside of cytotrophoblast - chorionic plate - E.E.M transversing chorionic cavity-connecting stalk (umbilical cord) **Fig.17. A 13-day human blastocyst (Sadler & Langman, 2019)** ## Notochord - A median cellular cord called the notochordal process migrates cranially from the primitive node until it reaches the prechordal plate, a small circular area of columnar ectodermal cells which is firmly attached to the overlying ectoderm. This will later form the buccopharyngeal membrane. - The primitive pit extends into the notochordal process and forms the notochordal canal. - The floor of the notochordal process fuses with the underlying intraembryonic endoderm of yolk sac. - The fused layers gradually undergo degeneration, resulting in openings in the floor of the notochordal process which brings the notochordal canal into communication with the yolk sac. - The opening becomes confluent and the floor of the notochordal process disappears. - A small opening called the neurenteric canal temporarily connects the yolk sac and amniotic cavity. - The disappearance of the floor of the notochordal process converts it into a flattened midline bar of mesoderm called the notochordal plate. - The plate detaches from the endoderm and forms a solid cord, the definitive notochord. - It forms a midline axis and supports the embryo. - It indicates the future site of the vertebral bodies. - As the vertebral column forms, the notochord in the region of the vertebral bodies disappear but they persist in the centre of the intervertebral disc as the nucleus pulposus – a semi-fluid jelly-like substance. - It induces the formation of the neural tube from the ectoderm overlying the notochord. **Fig.20. Formation of the notochord (Sadler & Langman, 2019)** ## Secondary Mesoderm - Secondary mesoderm is known as intraembryonic mesoderm. - It involves in the formation of organs and systems of the body. - During 3rd week of development, primitive streak appears with primitive node and primitive pit. - Cells of the epiblast migrate in the direction of the primitive streak. - On arrival in the region of the streak, they become flask-shaped, detach from the epiblast and slip beneath it (invagination). - Once the cells have invaginated, some migrates in lateral directions between the epiblast & hypoblast to form the secondary mesoderm or intraembryonic mesoderm. - Migration of the cells into the primitive streak occurs until the end of the 4th week after which it disappears. - They spread in lateral and cephalic directions beyond the margin of the disc. - Migrated cells contact with extra-embryonic mesoderm covering the yolk sac and amnion. - Secondary mesoderm spreads over the whole of the embryonic disc except: - in the median plane in the region of the notochord and - at the prechordal plate. ## The development of secondary mesodermal germ layer - Secondary mesoderm has 3 subdivisions; - Paraxial mesoderm - on each side of the notochord - Intermediate mesoderm - lateral to the paraxial mesoderm - Lateral plate mesoderm - lateral to the intermediate mesoderm - Initially, cells of the mesodermal germ layer form a thin sheet of loosely woven tissue on each side of the midline. - On 17th day, cells close to the midline proliferate and form a thickened plate of tissue known as paraxial mesoderm. - The mesodermal layer remains thin and is known as lateral plate mesoderm. - The lateral plate mesoderm is divided into two layers; somatic or parietal layer and splanchnic or visceral mesodermal layer. **Fig.21. The development of secondary mesodermal germ layer** ### Derivatives of secondary mesoderm 1. **Paraxial mesoderm** - Skeleton except skull - Muscles of head - Skeletal muscles of trunk and limb - Dermis of skin - Connective tissue 2. **Intermediate mesoderm** - Urogenital system including kidneys, gonads and their ducts. 3. **Lateral plate mesoderm** - Serous membrane of pleura, pericardium and peritoneum - Primitive heart - Blood and lymph cells - Connective tissue and muscles of viscera - Spleen - Suprarenal cortex ## Somites - Intraembryonic mesoderm on either side of notochord and neural tube proliferate to form paraxial mesoderm. - At the beginning of 3rd week, paraxial mesodermal cells become organized into segments known as somitomeres. - From occipital region caudally, somitomeres organized into somites. - But, 1st 7 pairs of somitomeres do not form somites. - At 20th day, first pair of somite appear in cervical region. - Then, new somites appear cephalo-caudally about 3 pairs per day until end of 5th week, 42 - 44 pairs are present. - They are 4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 8 - 10 coccygeal pairs. - 1st occipital and last 5 - 8 coccygeal somites later disappear. Remaining somites form axial skeleton. - During this period of development, age of embryo correlates to number of somites. ### Differentiation of Somites - Beginning of 4th week, somites surround the notochord and neural tube and are known as sclerotome. - The ventral portion of somites surrounds the notochord and forms the vertebral body and that surround the neural tube forms the vertebral arch. - Remaining dorsal somites known as dermomyotome. - Dermo-myotome gives rise to - Myotome - forming skeletal muscles - Dermatome - forming dermis and subcutaneous tissue - Hence, each somite forms its own sclerotome (cartilage and bone component) - its own myotome (segmental muscle component) and - its own dermatome (segmental skin component) - Each myotome and dermatome also has its own segmental nerve component. **Fig.22. Stages in the development of a somite (Sadler & Langman, 2019)** ## Derivatives of Germ Layers - Three germ layers are formed during gastrulation in 3rd week ### Derivatives of Ectoderm **A. Surface ectoderm** - Epidermis, hair and nails - Cutaneous (sweat glands & sebaceous glands) and mammary gland - Anterior pituitary gland - Epithelial lining of the cheek and gum, enamel of teeth - Epithelial lining of the lower part of anal canal and terminal part of urethra - Sensory epithelia of eye, ear and nose - Lens of the eye - Muscles of iris, arrectores pilorum muscles of skin and myoepithelial cells of the breast **B. Neuroectoderm** - Central nervous system and peripheral nervous system - Retina of eye - Pineal body - Posterior pituitary gland ### Derivatives of Mesoderm **A. Head mesoderm** - Skull - Connective tissue of head - Dentine of teeth **B. Paraxial mesoderm** - Muscles of head - Skeleton except skull - Connective tissue - Dermis of skin and - All skeletal muscles of trunk and limbs **C. Intermediate mesoderm** - Urogenital system including kidney, gonads and genital ducts **D. Lateral plate mesoderm** - Connective tissue and muscle of viscera - Serous membranes of pleura, pericardium and peritoneum - Primitive heart - Blood and lymph cells - Suprarenal gland (cortex) - Spleen ### Derivatives of Endoderm **A. Epithelial parts of** - Larynx - Trachea - Bronchi - Lungs - Pharynx - Thyroid gland - Tympanic cavity (middle ear cavity) - Pharyngotympanic tube - Tonsils - Parathyroid gland **B. Epithelium of** - Gastrointestinal tract - Liver - Pancreas - Urinary bladder - Urachus - Vagina and vestibule - Urethra and glands ## Fetal Membranes - Any tissues or structures develop from zygote but not take part in formation of embryo proper but they provide the growth and survival of embryo until the time of its independent existence. It includes yolk sac, amnion, chorion, allantois, umbilical cord and placenta. ### Umbilical cord - An oval unclosed area on the ventral surface of embryo at the amnioectodermal junction is known as primitive umbilical ring. ### Contents of the ring at 5th week: 1. **Connecting stalk** containing allantois and umbilical vessels (2 arteries and one vein). 2. **Vitelline duct** accompanied by vitelline vessels. 3. **Canal** connecting intra and extraembyonic celomic cavities. 4. **As amniotic cavity enlarges**: amnion envelops the connecting and yolk stalk to form primitive umbilical cord. 5. **The cord** contains yolk sac & umbilical vessels distally and intestinal loop & remnant of allantois proximally. 6. **At 3rd month**: amnion enlarges and obliterates the chorionic cavity. 7. **Later, allantois, vitelline duct and vitelline vessels are obliterated** and umbilical vessels are surrounded by Wharton's jelly. 8. **It serves as life line of the fetus.** 9. **The mature cord is 1-2cm in diameter** and average 55cm in length. 10. **Its insertion into placenta is nearly central.** **Fig. 23. A. Primitive umbilical ring at 5th week. B. primitive umbilical cord of 10th week embryo. C. Transverse section of primitive umbilical ring. D. Transverse section of umbilical cord (Sadler & Langman, 2019)** ### Anomalies of the cord - **Long cord**: - May coil around the fetus - Prolapse of umbilical cord between fetus and the mother's bony pelvis, causing compression of cord leading to fetal hypoxia - **Short cord**: - May cause premature separation of placenta from uterus during delivery - Absence of an umbilical artery - False knot of the cord due to longer umbilical vessels - True knot of the cord lead to fetal death **Fig. 24. A. False knot of umbilical cord. B. True knot of umbilical cord (Moore, 2016)** ### Yolk sac - **Primary Yolk Sac**: On 9th day of development, flattened cells from hypoblast form a thin membrane (Heuser's membrane) lining the inner surface of cytotrophoblast. - This membrane together with hypoblast form primary yolk sac. (see fig.15) - **Secondary yolk sac**: On 13th day of development, cells from hypoblast migrate along the inside of exocoelomic membrane. - A new cavity appears in exocoelomic cavity forming secondary or definitive yolk sac. - A large portion of exocoelomic cavity is pinched off forming exocoelomic cyst. - (see fig.17) ### Significance of Yolk Sac - Non-functional but essential for the following reasons - Transfer of nutrients to the embryo during 2nd & 3rd week when utero-placental circulation is established. - Formation of blood from yolk sac wall until haemopoietic activity begins in the liver during 6th week. - Some portion of yolk sac incorporating into embryo as primitive gut during the 4th week. - The endoderm of the yolk sac gives rise to epithelium of the trachea, bronchi, lungs and digestive tract. - Primordial germ cells appear in endodermal lining of wall of yolk sac. Later, they migrate to developing gonad and form oogonia in female and spermatogonia in male. **Fig. 25. A. A 3-week-old embryo showing primordial germ cells on the wall of yolk sac. B. Migratory pathway of primordial germ cells to the genital ridges (Sadler & Langman, 2019)** ### Allantois - Sausage like diverticulum appears from caudal wall of yolk sac extending into connecting stalk at 16th day of development. ### Importance - It is important for blood formation during 3rd to 5th week - Its blood vessels persist as one umbilical vein and arteries ### Fate - Extraembryonic portion degenerates during 2nd month - Intraembryonic portion forms urachus (median umbilical ligament) connecting the umbilicus and bladder ### Anomalies - Remnants of extraembryonic portion forms allantoic cyst (cystic mass in umbilical cord) - Remnants of intraembryonic portion forms urachal fistula/ cyst/ sinus ## Amnion - A small cavity appears in the epiblast during 8th day of development. This enlarges to form amniotic cavity. - At the end of 3rd month, this cavity fills the chorionic sac. - The amnion fuses with chorionic wall resulting in obliteration of chorionic cavity. **Fig. 27. Transverse section of embryo showing developmental stages of amnion (Sadler & Langman, 2019)** ### Amniotic fluid (Liquor Amnii) - Clear watery fluid that fills the sac. - Derived partly from amniotic cells and partly from maternal tissue fluid. - Plays a major role in fetal growth and development. - Amount of amniotic fluid is 30ml at 10 weeks, 450ml at 20weeks, 800-1000ml at 37weeks (see fig.16 &17) ### Circulation of Amniotic fluid - Water content changes every 3 hours - Large volume moves in both directions between maternal & fetal circulation - Fetus swallows the amniotic fluid as early as 5th month and it is absorbed by fetal respiratory and digestive tract. - Fetal urine is added daily to the amniotic fluid. ### Significance of Amniotic Fluid - Permits external growth of fetus - Acts as a barrier to infection - Cushions the fetus against injuries - Prevents the adherence of amnion to fetus - Permits normal fetal lung development - Enables the fetus to move freely there by aiding muscular development in the limbs - Helps to control embryo's body temperature - Involves in maintaining homeostasis of fluid and electrolytes - Helps in diagnosis of certain disorders in fetus by study of amniotic fluid - Helps to dilate the cervical canal by formation of hydrostatic wedge of amniochorionic membrane during child birth ### Anomalies - **Polyhydramnios** -an excess of amniotic fluid (1500 to 2000 ml) - idiopathic causes (35%) - maternal diabetes (25%), and - cogenital malformations of CNS (anencephaly) & of GIT (esophageal atresia) - **Oligohydramnios** - decreased amount (less than 400 ml) in renal agenesis. - Premature rupture of foetal membrane leads to - Oligohydramnios - Amniotic band - Premature labour and delivery ## Chorion (chorionic cavity) - Extraembryonic mesoderm (EEM) derived from yolk sac appears between the inner surface of cytotrophoblasts and outer surface of exocelomic cavity. - Small cavities appear within these cells and unite to form chorionic cavity. - EEM lining cytotrophoblast is known as chorionic plate. - This membrane forms chorionic villi later. (see fig.16 &17) ### Anomalies (trophoblast or ### Vesicular or hydatidiform mole - Complete or partial - Both types derived from abnormal fertilization involving two sperm or single abnormal diploid sperm (Eg. 69, XXY) - Abnormal proliferation of syncytiotrophoblasts and cytotrophoblasts forming swollen chorionic villi (grapes like vesicles) - High level of hCG in maternal blood ### Choriocarcinoma - 50% of choriocarcinoma arises from complete hydatidiform mole - Appears as haemorrhagic necrotic uterine mass without formation of definite placental type villi - Lesion in uterus usually regresses completely, leaving only metastases to lungs (50%) and other tissues ## Placenta - As the human embryo grows its need for nutrition increases, requiring a connection to the mother for nutrient, gas and waste exchange. - Placenta develops to meet these needs. - Placenta is a feto-maternal organ connecting the