Embryology Final PDF

34 Fertilization; Cleavage & Implantation ILOs By the end of this lecture, students will be able to 1. Correlate the structure of sperm and ovum with the process of fertilization. 2. Evaluate role of mitochondria & flagellum in sperm motility. 3. Justify inheritance of...

34 Fertilization; Cleavage & Implantation ILOs By the end of this lecture, students will be able to 1. Correlate the structure of sperm and ovum with the process of fertilization. 2. Evaluate role of mitochondria & flagellum in sperm motility. 3. Justify inheritance of mitochondria from the mother in view of sperm structure. 4. Interpret steps and results of normal fertilization. 5. Distinguish the cascade of cleavage till implantation. 6. Correlate the mechanisms and site of implantation to clinical conditions resulting from their dysregulation. Fertilization Definition: it is the process by which mature sperm and mature ovum meet and fuse forming the zygote. Site: At the ampullary part (lateral third) of the uterine tube. Stages: Spermatozoa are not able to fertilize the oocyte immediately upon arrival in the female genital tract but must undergo capacitation and the acrosome reaction to acquire this capability. Parts of the seprmatozoa ⮚ Spermatozoa are composed of a head, housing the nucleus, and a tail that is divided into four regions: neck, middle piece, principal piece, and end piece. (Fig 1) ⮚ Head of the spermatozoa; It is occupied by the condensed electron-dense nucleus, containing only 1 member of the 23 pairs of chromosomes (22 autosomes + the Y chromosome-or 22 autosomes + the X chromosome), and the acrosome, which partially surrounds the anterior aspect of the nucleus. ⮚ Middle piece; contains a mitochondrial sheath that provides energy needed for sperm motility. Thus, mitochondria are present outside the head. Mitochondria are inherited from the mother only. ⮚ Tail (flagellum); houses the axoneme that has a structure similar to the cilia and responsible for sperms motility. (Fig. 1) ⮚ Role of head in fertilization; the acrosome comes into contact with the cell membrane of the spermatozoon anteriorly. It houses various enzymes, including neuraminidase, hyaluronidase, acid phosphatase, aryl sulfatase, and a trypsin-like protease known as acrosin. Fertilization steps Page 1 of 7  Capacitation: is a period of conditioning in the female reproductive tract; in human it lasts approximately 7 hours. During this time, a glycoprotein coat and seminal plasma proteins are removed from the plasma membrane that overlies the acrosomal region of the spermatozoa. Acrosome reaction: which occurs after binding of the head to the zonapellucida, is induced by zona proteins; enzymes needed to penetrate the zonapellucida are released including acrosin- and trypsin-like substances. Figure 1. Parts of the spermatozoa Phases of fertilization: ⮚ Phase 1, penetration of the corona radiate. ⮚ Phase 2, penetration of the zona pellucida. ⮚ Phase 3, fusion of the oocyte and sperm head cell membranes. Results of fertilization: ⮚ Restoration of the diploid number of chromosomes. ⮚ Determination of the sex of the new individual.(How?) ⮚ Initiation of cleavage: without fertilization, the oocyte usually degenerates 24 hours after ovulation. Page 2 of 7  Figure 2. Structure of the ovum Cleavage Definition:is a series of mitotic divisions that results in an increase in cells. Site: The uterine tube, medial to the ampulla. Stages of cleavage: A. Morula stage: Page 3 of 7 About 30 hours after fertilization, the zygote divides into 2 cells (blastomeres), then into 4 blastomeres at 40 hours. - Twelve cell stage is reached after 3 days of fertilization, while the 16 cell stage is reached at the 4th day. The developing embryo of 12 – 16 blastomeres is called morula that enters the uterus nearly 3 days after fertilization. The morula gets its nutrition from its own cytoplasm. B. Blastocyst formation: As the morula enters the uterus, fluid from the uterine cavity penetrates through the zona pellucida and coalesces to form a single cavity (the blastocele) and the embryo is called blastocyst. The blastocele divides the blastomeres into inner cell mass which will form the embryo proper. The surrounding cells of the periphery form the outer cell mass which will form the trophoblast that will form the fetal part of the placenta. The cells of the inner cell mass are now called the embryoblast and are located at one pole of the blastocyst. The zona pellucida disappears immediately before implantation. Events during the first week of human development. 1, oocyte immediately after ovulation; 2, fertilization,approximately 12 to 24 hours after ovulation; 3, stage of the male and female pronuclei; 4, spindle of the first mitotic division;5, two-cell stage (approximately 30 hours of age); 6, morula containing 12 to 16 blastomeres (approximately 3 days ofage); 7, advanced morula stage reaching the uterine lumen (approximately 4 days of age); 8, early blastocyst stage (approximately 4.5 days of age; the zonapellucida has disappeared); and 9, early phase of implantation (blastocyst approximately 6 days of age). The ovary shows stages of transformation between a primary follicle and a preovulatory follicle as well as a corpus luteum. The uterine endometrium is shown in the progestational stage. Implantation Page 4 of 7 Definition: It means penetration of the blastocyst into the superficial (compact) layer of the uterine endometrium.(What happens if the implantation extends deeper than this?) Time: Starts by the end of the first week (6th day), and is completed about the 11th day. Normal site of implantation: is the endometrium of the anterior or posterior wall of the body of the uterus in or near the middle line. Mechanism of implantation: While floating freely in the uterus, the embryo gets nourishment from secretions of the uterine glands. About 6 days after fertilization, the blastocyst at the inner cell mass side (embryonic pole) attaches to the endometrium after disappearance of zonapellucida. The trophoblast proliferates rapidly and becomes differentiated into two layers: A. An inner cellular layer of cytotrophoblast. B. An outer multinucleated protoplasmic mass with no cell boundaries called syncytiotrophoblast. -The syncytiotrophoblast forms finger like processes that extend into the endometrium of the uterus. By the end of the first week, the blastocyst is superficially implanted in the compact layer of the endometrium. - The syncytiotrophoblast at the embryonic pole expands quickly. It produces enzymes that erode the uterine maternal tissues, so enabling the blastocyst to burrow into the endometrium. This implanted blastocyst gets its nourishment from the eroded maternal uterine tissues. After complete blastocyst implantation, the endometrium is called "decidua". THE DECIDUA Definition: It is the compact layer of the endometrium after implantation of the blastocyst. Types of the decidua: 1. Decidua basalis: It is the part of endometrium lying at the base of the implanted blastocyst, between it and the myometrium of the uterus. It will form the maternal origin of the placenta. 2. Decidua capsularis: It is the part of endometrium covering the surface of the implanted blastocyst; it lies between the blastocyst and the uterine cavity. 3. Decidua parietalis: It is the part of endometrium lining the rest of the uterine cavity. 4. Decidua marginalis: It is the part of endometrium lying at the junction between decidua capsularis and parietalis (It lies at the margins of the implanted blastocyst). - The last three types of decidua will ultimately fuse and degenerate with the advance of pregnancy due to growth of the fetus. Page 5 of 7 The early stages of human placental development. Diagram depicting the early steps in placenta formation following blastocyst implantation. (A,B) The pre-lacunar stages. (C) The lacunar stage. (D) The primary villous stage. 1° ys, primary yolk sac; ac, amniotic cavity; cs, cytotrophoblastic shell; eec, extra-embryonic coelom; exm, extra-embryonic mesoderm; GE, glandular epithelium; ICM, inner cell mass; lac, lacunae; LE, luminal epithelium; mn. tr, mononuclear trophoblast; pr. syn, primary syncytium; TE, trophectoderm; vs, blood vessels. Development. CLINICALCORRELATES ❖ The syncytiotrophoblast is responsible for hormone production, including human chorionic gonadotropin (hCG). By the end of the second week, quantities of this hormone are sufficient to be detected by radioimmunoassays.(What is its significance?) ❖ Abnormal implantation (Ectopic pregnancy): It is implantation of the blastocyst in any place other than the normal site. It might result in death of the embryo or early abortion with severe internal haemorrhage. Abnormal sites of implantation: 1. Uterine ectopic pregnancy: a. At the cornu of the uterus (the site of attachment of the uterine tube) leading to early abortion. b. At the lower uterine segment or cervix leading to placenta previa. 2. Extra uterine ectopic pregnancy: a. The commonest site is in the fallopian tube. (What will be the results?) b. Ovary (ovarian pregnancy). Page 6 of 7  c. Peritoneum of Douglas pouch (abdominal pregnancy), broad ligament of the uterus, or omentum of the stomach (rare). ❖ Placenta previa: means implantation of the blastocyst in the lower segment of the uterus close to the internal os of the cervix. Thus the placenta will precede the foetus at delivery (normally, the foetus delivered first, followed by the placenta). (What will be the result of that?) Page 7 of 7 37 The Second& Third Weeks of Development ILOs By the end of this lecture, students will be able to 1. Analyze the changes occurring during the 2nd & 3rd weeks of development. 2. Recognize different types of stem cells in relation to stages of fetal development & the significance of their differentiation potential 3. Interpret the process of gastrulation. 4. Correlate the process of gastrulation with teratogenesis, and other clinical disorders. Changes occurring during the second week of development: At the beginning of the second week, the blastocyst is partially embedded in the endometrial stroma. 1- The trophoblast differentiates into two layers: (a) Inner, actively proliferating layer, the cytotrophoblast, (b) Outer, the syncytiotrophoblast, which erodes maternal tissues. By day 9, lacunae (cavities) develop in the syncytiotrophoblast. Subsequently, maternalsinusoids are eroded by the syncytiotrophoblast; maternal blood enters the lacunar network, and by the end of the second week, a primitive uteroplacentalcirculation begins. The cytotrophoblast, meanwhile, forms cellular columns penetrating into and surrounded by the syncytium. These columns are primary villi. By the end of the second week, the blastocyst is completely embedded, and the surface defect in the mucosa has healed. 2- The inner cell mass or embryoblast, meanwhile, differentiates into: (a)the epiblastand (b) the hypoblast, together forming a bilaminar disc. Epiblast cells give rise to amnioblaststhat line the amniotic cavity superior to the epiblast layer. Endoderm cells are continuous with the exocoelomic membrane (that lines the inner surface of the cytotrophoblast), and together they surround the primitive yolk sac. 3- By the end of the second week, extraembryonic mesoderm fills the space between the trophoblast externally, and the amnion and exocoelomic membrane internally. When vacuoles develop in this tissue, the extraembryonic coelom or chorionic cavity forms. Page 1 of 6  The extraembryonic mesoderm lining the cytotrophoblast and amnion is called the extraembryonicsomatopleuric mesoderm; the lining covering the yolk sac is known as the extraembryonicsplanchnopleuric mesoderm. Summary:The second week of development is the week of twos, because of the following: Trophoblast differentiates into 2 layers, (Nominate theses 2 layers) Inner cell mass differentiates into 2 layers, (Nominate theses 2 layers) Primary mesoderm splits into somatopleuric primary mesoderm &splanchnopleuric primary mesoderm. Starting of formation of the amniotic and yolk sac cavities. Stages of development of the embryo during the 2nd week. A. Late blastocyst. B, Beginning of implantation at 6 days. The hypoblast has formed and is beginning to spread beneath the cytotrophoblast as the endoderm. C. Implanted blastocyst at 7 days. D. Implanted blastocyst at 8 days. E. Embryo at 9 days. F. Late second week. Page 2 of 6 A 9-day human blastocyst. The syncytiotrophoblast shows a large numberof lacunae. Flat cells form the exocoelomic membrane. The bilaminar disc consists of a layer of columnar epiblast cells and a layer of cuboidal hypoblast cells. The original surface defect is closed by a fibrin coagulum. Differentiation of Extraembryonic mesoderm What is the final product of the first week of development?(slideplayer.com) Page 3 of 6 Embryonic stem cells Stem cells are undifferentiated (unspecialized) cells that have the following properties: 1. Self-renewal: it is the ability of the cell to go through numerous cycles of cell division while maintaining the undifferentiated state. 2. Potency: it is the capacity to differentiate into different cell types. Embryonic stem cells: these are totipotent stem cells that can differentiate into any other types of cells. Clinical Hint: Stem cells have an important role in treatment of many diseases because of their ability to differentiate into different cell types in cell cultures. These cells can be transplanted into the patient to regenerate the damaged cells. Sources of stem cells: a. Embryonic cells that are of limited use due to ethical restriction. b. Adult cells; can be obtained from several sources such as the bone marrow. They are (multipotent) less potent than embryonic stem cells as they can differentiated into limited number of cell types. Figure.Embryonic stem cells Changes occurring during the third week of development: (TRILAMINAR GERM DISC) GASTRULATION: (Formation of Embryonic Germ layers) It is the process by which the bilaminar embryonic disc is converted into a trilaminar embryonic disc. Gastrulation begins with formation of a midline groove on the surface of the epiblast of the embryonic disc with elevated edges, it is called primitive streak. Page 4 of 6  The cephalic end of this steak is called primitive node. A groove appears at the center of the node called primitive pit. Cells of the ectoderm (epiblast) migrate in the direction of the primitive streak; they slip under the epiblastic layer through the primitive streak to replace the hypoblast andform the endodermal layer of embryonic disc. Then, some of invaginatedepiblastic cells form the intraembryonic mesoderm, thus, the ectoderm or the epiblast is the source of the three germ layers of the embryo). The intraembryonic mesoderm migrates in all directions forming a complete layer of cells separating the ectoderm dorsally from the endoderm ventrally except at the area of the oral membrane and the cloacal membrane. Formation of the notochord: Some mesenchymal cells migrate cranially from the primitive node and pit (deep to epiblast), forming a median cellular cord; the notochord.. A. Dorsal side of the germ disc from a 16-day embryo indicating the movement of surface epiblast cells (solid black lines) through the primitive streak and node and the subsequent migration of cells between the hypoblast and epiblast (broken lines). B. Cross section through the cranial region of the streak at 15 days showing invagination of epiblast cells. The first cells to move inward displace the hypoblast to createthe definitive endoderm. Once definitive endoderm is established, inwardly moving epiblastforms mesoderm. Functions of the notochord: 1. It forms the axis around which the axial skeleton develops. 2. It stimulate the overlying ectoderm to form the central nervous system. 3. The notochord degenerates and disappears as the bodies of the vertebrae form. Its remnant is the nucleus pulposus of the intervertebral discs. (What is the intervertebral discs?) Page 5 of 6 CLINICAL APPLICATION: Gastrulation may be disrupted by genetic abnormalities and toxic insults. In caudal dysgenesis (sirenomelia), insufficient mesoderm is formed in the caudal-most region of the embryo. Because this mesoderm contributes to formation of the lower limbs, urogenital system, and lumbosacral vertebrae, abnormalities in these structures occur. Affected individuals exhibit a variable range of defects, including hypoplasia and fusion of the lower limbs, vertebral abnormalities, renal agenesis, imperforate anus ,and anomalies of the genital organs. In humans, the condition is associated with maternal diabetes and other causes. At the end of the fourth week, the primitive streak shows regressive changes, rapidly shrinks and soon disappears. Sometimes, remnants of the primitive streak persist in sacrococcygeal region. These pluripotent cells proliferate and form tumors known as sacrococcygealteratomas. Caudal dysgenesis (sirenomelia) Sacrococcygealteratoma Page 6 of 6  38 The Embryonic period ILOs By the end of this lecture, students will be able to 1. Interpret the importance of embryonic folding during development. 2. Differentiate between the derivatives of the three germ layers. 3. Appraise their dysregulated development in occurrence of birth defects 4. Distinguish how the timeline of embryogenesis is the most sensitive period for teratogens and structural defects. The embryonic period or period of organogenesis, occurs from the third to the eighth weeks of development and is the time when each of the three germ layers, ectoderm, mesoderm, and endoderm, gives rise to a number of specific tissues and organs. Also, folding of the embryo occurs at the beginning of this period. FOLDING OF THE EMBRYO Definition: Conversion of the flat trilaminar embryonic disc into a cylindrical embryo. Time: begins by the end of the 3rd week. It is completed by the 4th week. Types: 1. Cephalocaudal folding (head fold & tail fold): It is caused by the rapid longitudinal growth of the central nervous system. A. The head fold: Before folding: the following structures are present in the midline of intraembryonic mesoderm arranged in a craniocaudal direction: a. septum transversum (future central tendon of diaphragm) b. cardiogenic plate (future heart) the pericardial cavity lies dorsal to the cardiogenic plate. c. Oral membrane (future mouth opening). Late in folding: The following structures lie ventral to the embryo and arranged in a craniocaudal order: a. Oral membrane, b. Cardiogenic plate, c. Septum transversum. Due to folding, a constriction appears at the junction of the embryo and yolk sac. Part of the endodermal yolk sac is included in the cranial part of the embryo it is called foregut. B. Tail fold: Page 1 of 5 Before folding, the allantois is caudal to the yolk sac. The yolk sac lies ventral to the endodermal layer of embryonic disc. The cloacal membrane lies in the caudal part of the embryo. After folding: The allantois and the cloacal membrane shifted ventrally to the embryo. Part of the yolk sac incorporated in the caudal part of the embryo forming the hind gut. The terminal part of hind gut dilates to form the cloaca (future urinary bladder and rectum) Sagittal midline sections of embryos at various stages of development to demonstrate cephalocaudal folding and its effect on position of the endoderm-lined cavity. A. Presomite embryo. B. Embryo with 7 somites. C. Embryo with 14 somites. D. End of the first month. Note the angiogenic cell clusters in relation to the buccopharyngeal membrane. 2. Lateral folding (right and left folds) It is due to the rapid growth of the somite (part of intraembryonic mesoderm). Lateral folding lead to formation of midgut, also it leads to constriction of the wide communication between the extraembryonic ceolom and midgut. This constricted communication called vitellointestinal duct or yolk stalk. The amniotic cavity increases in size on expense of the extraembryonic coelom. Page 2 of 5 Transverse sections through embryos at various stages of development to show the effect of lateral folding on the endoderm-lined cavity. A. Folding is initiated. B. Transverse section through the midgut to show the connection between the gut and yolk sac. C. Section just below the midgut to show the closed ventral abdominal wall and gut suspended from the dorsal abdominal wall by its mesentery. Results of folding: 1. It gives the embryo its cylindrical form. 2. Formation of the gut. 3. As a result of formation of the head fold: the buccopharyngeal membrane, heart & septum transversum become ventral in position and arranged in a craniocaudal order. 4. As a result of formation of the tail fold: the cloacal membrane and allantois become ventral in position. 5. The umbilical cord is formed and the connecting stalk is shifted ventrally. 6. The allantois becomes ventral instead of dorsal. Differentiation& Derivatives of the three germ layers: Differentiation of the secondary (intra-embryonic) mesoderm: Secondary mesoderm is divided into three columns on each side of the notochord. 1. The paraxial mesoderm: - It is the medial part that lies on either side of the notochord. - It is divided by transverse grooves into body blocks called somites (4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 8-10 coccygeal). - The somites give the axial skeleton (bones & cartilage), vertebral muscles and covering skin. 2- The intermediate cell mass (or nephrogenic cord). It gives rise to the urinary and genital systems. 3. The lateral plate of mesoderm: Page 3 of 5 - A cavity appears in the lateral plate of mesoderm called the intraembryonic coelom. This ceolom splits the lateral plate of mesoderm into two layers, the somatic and splanchnic layers. A. The somatic layer: gives the muscles of body wall. B. The splanchnic layer: It lies next to the endoderm. It gives the smooth or involuntary muscles (heart, bronchial tree & gut) Differentiation of the intraembryonic mesoderm Endodermal Derivatives: The endodermal germ layer provides the epithelial lining of the gastrointestinal tract, respiratory tract, and urinary bladder. It also forms the parenchyma of the thyroid, parathyroids, liver, and pancreas. Ectodermal Derivatives: The ectodermal germ layer gives rise to the organs and structures that maintain contact with the outside world: (a) central nervous system; (b) peripheral nervous system; (c) sensory epithelium of ear, nose, and eye; (d)skin, including hair and nails; and (e) pituitary, mammary, and sweat glands and enamel of the teeth. Neurulation: The neural plate appears as a thickening of embryonic ectoderm induced by the developing notochord. A longitudinal neural groove develops in the neural plate, which is flanked by neural folds. Fusion of the folds forms the neural tube (the primordium of the central nervous system). As the neural folds fuse to form the neural tube, neuroectodermal cells form a neural crest between the surface ectoderm and the neural tube. Page 4 of 5  Formation of the neural tube; A: Day 17; B: Day 19; C: Day 20; D: Day 21 neuroembryology Flashcards | Quizlet C L I N I C A L C O R R E L A T E S: Birth Defects Most major organs and organ systems are formed during the third to eighth week. This period, which is critical for normal development, is therefore called the period of organogenesis. Neural tube defects can develop during this period due to abnormal neurulation process. Page 5 of 5  39 The Fetal Membranes ILOs By the end of this lecture, students will be able to 1. Differentiate between the different fetal membranes & correlate that to their possible abnormalities. 2. Recognize the clinical importance of amniotic fluid in diagnosis of genetic defects. 3. Interpret how trophoblastic disorders contribute to development of preeclampsia. Fetal membranes are the chorion, amnion, yolk sac, allantois. They develop from the zygote but do not form parts of the embryo. 1- Chorion: It consists of syncytiotrophoblast, cytotrophoblast and primary mesoderm (extra- embryonic mesoderm). - By the beginning of the third week, the trophoblast is characterized by primary villi that consist of a cytotrophoblastic core covered by a syncytiotrphoblast. Then, mesodermal cells penetrate the core of primary villi and grow toward the decidua. The newly formed structure is known as a secondary villus. By the end of the third week, mesodermal cells in the core of the villus begin to differentiate into blood cells and small blood vessels, forming the villous capillary system. The villus is now known as a tertiary villus. Later on, capillaries in tertiary villi are connected to blood vessels of umbilical cord and placenta. - Fate of villi: In the early weeks of development, villi cover the entire surface of the chorion. As pregnancy advances, villi on the embryonic pole continue to grow and expand, giving rise to the chorion frondosum (bushy chorion). Villi opposite decidua capsularis degenerate, giving rise to the chorion leave (smooth). - Types of villi according to Function: Villi that extend from the chorionic plate to the decidua basalis (decidual plate: the part of the endometrium where the placenta will form) are called anchoring villi (fixative). Those that branch from the sides of anchoring villi are free villi (nourishing) through which exchange of nutrients and other factors will occur. Page 1 of 5 CLINICAL CORRELATION: In some cases, the trophoblast develops and forms placental membranes, although little or no embryonic tissue is present. Such a condition is known as a hydatidiform mole. Moles secrete high levels of hCG and may produce benign or malignant (invasive mole, choriocarcinoma) tumors. insufficient invasion of trophoblast cells into the myometrial portions of the spiral arteries is thought to play a crucial role in the development of preeclampsia. Uteroplacental vessels fail to provide a sufficient blood supply to the placenta. So, placental hypoxia causes secretion of placental metabolites resulting in pregnancy- induced hypertension. 2- Amnion: At the beginning of the 2nd week, a small cavity appears within the epiblast. This cavity enlarges to become the amniotic cavity which is filled by amniotic fluid. Epiblast cells adjacent to the cytotrophoblast are called amnioblasts; together with the rest of the epiblast, they line the amniotic cavity. (What are the structures forming the roof and floor of amniotic cavity?) As the embryo fold on itself, the amniotic cavity expands greatly (on the expense of extra embryonic coelom) and surrounds the embryo from all sides. So, the embryo float in the amniotic fluid which fill the cavity. Sources of amniotic fluid: 1. Maternal blood: by transport across the amnion from the placenta. 2. Amniotic membrane cells 3. Fetal urine (major component): The kidney start functioning from the 4th month. Composition of amnion: It is a clear watery fluid (98% water) containing 2% salts, emzymes and hormones. Volume: one liter at the end of pregnancy. The volume is replaced every 3hours. Functions: 1. Protects the embryo from shocks. 2. Prevents adhesion of amniotic membrane to the growing embryo. 3. Allows free movement of the embryo to permit muscular growth. 4. Permits symmetrical external environment for growth of the embryo. Page 2 of 5  5. Learns the embryo how to suckle. 6. Keep constant temperature around the embryo. During labour: It forms the fore bag of water which allows dilatation of the cervix. After its rupture, it washes the cervix, lubricate it for the descend of the baby and acts as bacteriostatic. Abnormalities (CLINICAL CORRELATION): 1. Polyhydramnios: The volume exceeds 1.5- 2 liters. It may be due to anencephaly, esophageal atresia or maternal diabetes. 2. Oligohydramnios: The volume is less than half a liter. It may be due to renal agenesis or placental insufficiency. (That is the result of this abnormality?) 3. Caul de sac: The fetus is delivered with the amniotic membrane intact. (How can we deal with it?) Development of fetal membranes in the different stages of embryonic development 3- Yolk sac: During the 2nd week of development, flattened cells originating from the hypoblast form a thin membrane, the exocoelomic (Heuser’s) membrane, that lines the inner Page 3 of 5  surface of the cytotrophoblast. This membrane, together with the hypoblast, forms the lining of the exocoelomic cavity, or primitive yolk sac. After that, the hypoblast produces additional cells that migrate along the inside of the exocoelomic membrane which form a new cavity within the exocoelomic cavity. This new cavity is the secondary yolk sac or definitive yolk sac which is smaller than the primitive yolk sac. As a result of cephalocaudal folding, a larger portion of the yolk sac is incorporated into the body of the embryo proper, in the anterior part, forming the foregut; in the tail region, it forms the hindgut. The part between foregut and hindgut is the midgut. The midgut temporarily communicates with the yolk sac by the yolk stalk (vitelline duct). This duct is wide but with further growth of the embryo, it becomes narrow and much longer and degenerates. Functions of yolk sac: Its endoderm gives the mucous membrane of gastrointestinal tract, respiratory system and most of urinary bladder. Primordial germ cells present in the wall of yolk sac migrate to the site of ovary and testis to form the ova and sperms. Splanchnic mesoderm covering the yolk sac forms blood cells and vitelline blood vessels. Abnormalities (CLINICAL CORRELATION) of yolk sac: 1. Foecal umbilical hernia: due to persistence of all the yolk sac. 2. Meckel’s diverticulum: due to persistence of a part of yolk sac attached to the intestine (ileum). It is 2 inches long, 2 feet away from the ileocaecal junction and occurs in about 2% of population. 3. Fibrous band: Yolk stalk obliterates and is changed into a fibrous band which may lead to intestinal obstruction. 4. Vitelline sinus and cyst: (what is the cause of each?) Congenital anomalies of yolk sac Page 4 of 5 4- Allantois: When the cloacal membrane appears, the posterior wall of the yolk sac forms a small diverticulum that extends into the connecting stalk. This is the allantois. An important result of cephalocaudal folding is partial incorporation of the allantois into the body of the embryo, where it forms the cloaca. The distal portion of the allantois remains in the connecting stalk. By the end of folding, the yolk stalk, allantois, and umbilical vessels shifted to the region of the umbilical ring. Functions of allantois: The primary mesoderm of the connecting stalk surrounding the allantois gives the umbilical blood vessels. Fate of allantois: Intraembryonic part of allantois obliterates to give the uracus which persists as median umbilical ligament after birth. Abnormalities (CLINICAL CORRELATION) of allantois: 1. Urachal syst 2. Urachal sinus 3. Urachal fistula (What is the cause of each?) Fate of allantois (After birth it obliterates to form the median umbilical ligament attached to the apex of urinary bladder) Congenital anomalies of allantois Page 5 of 5  40 The Placenta And Umbilical Cord ILOs By the end of this lecture, students will be able to 1. Differentiate between the origin and structure of the placenta & umbilical cord. 2. Interpret the causes of congenital anomalies of the placenta & umbilical cord. 3. Correlate postnatal changes of umbilical cord to its congenital anomalies. 4. Value the structural importance of placental barrier and correlate that with clinical conditions that develop when breeched. BLACENTA Origin of placenta: By the beginning of the fourth month, the placenta has two components: (a) A fetal portion, formed by the chorion frondosum; and (b) A 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, of which the decidual plate is most intimately incorporated. Development of placenta: Between the chorionic and decidual plates are the intervillous spaces, which are filled with maternal blood. During the fourth and fifth months the decidua forms a number of decidual septa, which project into intervillous spaces but do not reach the chorionic plate. 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. As a result of this septum formation, the placenta is divided into compartments, or cotyledons. Since the decidual septa do not reach the chorionic plate, contact between intervillous spaces in the various cotyledons is maintained. Origin and development of placenta 1  Structure of placenta Full term placenta: At full term, the placenta is discoid with a diameter of 15 to 25 cm, is 3 cm thick, and weighs about 500 to 600 g. At birth, it is torn from the uterine wall and, approximately 30 minutes after birth of the child, is expelled from the uterine cavity. After birth, when the placenta is viewed from the maternal surface, 15 to 20 cotyledons, are clearly recognizable and it is reddish and rough. Grooves between the cotyledons are formed by decidual septa. The fetal surface of the placenta is whitish and smooth because it is covered by the amnion. Attachment of the umbilical cord is usually central or eccentric. Placental circulation: It is divided into: 1- Maternal circulation: Cotyledons receive their blood through 80 to 100 spiral arteries that pierce the decidual plate and enter the intervillous spaces. Oxygen and nutrients from maternal blood passes through placental barrier into umbilical vein to the fetus. At the same time, CO2 and waste products passes from the umbilical artery of the fetus to the placenta through the barrier. 2- Fetal circulation: The two umbilical arteries carry fetal blood containing CO2 and waste products which passes to the placenta through placental barrier. At the same time, oxygen, nutrients pass from maternal blood into umbilical vein to the fetus. Functions of placenta: 1- Nutrition: Nutrients pass from the mother to the fetus. 2- Excretion: Waste products pass from the fetus to the mother. 3- Respiration: Oxygen and CO2 are exchanged between the mother and fetus. 4- It Prevents toxins, drugs and microorganisms to pass from the mother to fetus. 2  5- Production of hormones like progesterone, estrogen and HCG. Placental circulation and exchange of materials between maternal and fetal blood Placental barrier (membrane): Definition: They are the structures separating fetal blood from maternal blood (wall of tertiary villi). They prevent mixing of fetal and maternal blood and allow exchange of gases and passage of nutrients and waste products. Structure: 1- The placental membrane is initially composed of four layers: (a) the endothelial lining of fetal vessels; (b) the primary mesoderm; (c) the cytotrophoblast; and (d) the syncytiotrophoblast. 2- From the fourth month on, the placental membrane thins, since the endothelial lining of the vessels comes in intimate contact with the syncytial membrane, greatly increasing the rate of exchange. What are the layers forming the barrier? 3- At the end of pregnancy, permeability must decrease, so, fibrinoid material is deposited on the outer surface. What are the layers forming the barrier? ▪ The placental membrane is not a true barrier, since many substances pass through it freely. Placental barrier at the different stages of pregnancy 3  UMBILICAL CORD Full term umbilical cord: ▪ At birth, the umbilical cord is approximately 2 cm in diameter and 50 to 60 cm long. It is tortuous, causing false knots. ▪ Normally there are two arteries and one vein in the umbilical cord pathed in Warton’ jelly). What is it? Transverse section of a definitive umbilical cord Development of umbilical cord: 1- Primitive umbilical cord: It is formed during folding. It contains: a. Body stalk containing allantois and umbilical blood vessels. b. Yolk stalk and vitelline blood vessels. c. The remaining part of extra embryonic coelom. 2- Definitive umbilical cord: Extra embryonic coelom and allantois obliterate Why? and yolk stalk degenertates. So, it will contain Umbilical blood vessels and Wharton’s jelly covered by amniotic membrane. Structures passing through the primitive umbilical ring and umbilical cord 4 Abnormalities (CLINICAL CORRELATION) of placenta and umbilical cord: 1- Bilobed or triloped placenta. 2- Accessory placenta. 3- Placenta praevia: It may be; a. Centralis b. Marginalis c. Parietalis which leads to antepartum haemorrhage. So, delivery must be by ceasarian section. 4- An extremely long cord may encircle the neck of the fetus, usually without increased risk, whereas a short one may cause difficulties during delivery by pulling the placenta from its attachment in the uterus. What is the result of this anomaly? 5- Presence one artery only Why? These babies have approximately a 20% chance of having cardiac and other vascular defects. 6- Anomalies in the attachment to placenta: marginal attachment or insertion into the chorionic membranes outside the placenta (velamentous insertion). 7- Exomphalos (Omphalocele): Due to failure of a loop of the intestine to return to the abdominal cavity after herniation. The protruded part is covered by amniotic membrane. Abnormalities of placenta and umbilical cord 5  41 2nd & 3rd trimester (Developmental Landmarks) ILOs By the end of this lecture, students will be able to 1. Summarize the key events during the fetal period. 2. Interpret the developmental horizons during fetal life event. 3. Apply these events to explain clinical correlations, as low birth defects. Fetal period Definition: The period from the beginning of the ninth week to birth. It is characterized by: 1- maturation of tissues and organs. 2- rapid growth of the body. ▪ The length of pregnancy is about 40 weeks after the onset of the last normal menstrual period or 38 weeks after fertilization. Monthly changes: One of the most striking changes taking place during fetal life is the relative slowdown in growth of the head compared with the rest of the body. At the beginning of the third month the head constitutes approximately half of the CRL (crown rump length) (what is it?). By the beginning of the fifth month, the size of the head is about one-third of the CHL, and at birth it is approximately one-fourth of the CHL. So, over time, growth of the body accelerates but that of the head slows down. Size of the head in relation to the rest of the body at various stages of development. A. 3rd month B. 5th month C. At birth Page 1 of 4 During the 3rd month: ▪ the face becomes more human looking. ▪ The limbs reach their relative length in comparison with the rest of the body, although the lower limbs are still a little shorter and less well developed than the upper extremities. ▪ Primary ossification centers are present in the long bones and skull by the 12th week. ▪ Also, by the 12th week, external genitalia develop to such a degree that the sex of the fetus can be determined by external examination (ultrasound). ▪ During the 6th week intestinal loops cause a large swelling (herniation) in the umbilical cord, but by the 12th week the loops withdraw into the abdominal cavity. During the 4th and 5th months: ▪ The fetus lengthens rapidly. ▪ The weight of the fetus increases little during this period and by the end of the fifth month is still less than 500 g. ▪ The fetus is covered with fine hair, called lanugo hair. ▪ Eyebrows and head hair are also visible. ▪ During the fifth month movements of the fetus can be felt by the mother (Quikening). During the 2nd half of intrauterine life: ▪ The weight increases considerably, particularly, during the last 2.5 months, when 50% of the full-term weight (approximately 3200 gm) is added. During the 6th month: ▪ The skin of the fetus is reddish and has a wrinkled appearance because of the lack of underlying connective tissue. ▪ Although several organ systems are able to function, the respiratory system and the central nervous system have not differentiated sufficiently. During the last two months: ▪ The fetus obtains well-rounded contours as a result of deposition of subcutaneous fat. ▪ By the end of intrauterine life, the skin is covered by a whitish, fatty substance (vernix caseosa) composed of secretory products from sebaceous glands. Event Age/ week Taste buds appear 7 Swallowing 10 Respiratory movements 14–16 Sucking movements 24 Some sounds can be heard 24–26 Eyes sensitive to light 28 Some developmental events (horizons) occurring during the fetal life Page 2 of 4 At the end of 9th month: ▪ The skull has the largest circumference of all parts of the body, an important fact with regard to its passage through the birth canal. ▪ At the time of birth, the weight of a normal fetus is 3000 to 3400 gm; ▪ Its CRL is about 36 cm; and its CHL (crown heal length) (what is it?). is about 50 cm. ▪ Sexual characteristics are pronounced, and the testes should be in the scrotum. 12 weeks baby 28 weeks baby Page 3 of 4 Clinical correlation: 1- Low Birth Weight: There is considerable variation in fetal length and weight, and sometimes these values do not correspond with the calculated age of the fetus in months or weeks. Most factors influencing length and weight are genetically determined, but environmental factors also play an important role. 2- Intrauterine growth restriction (IUGR) Approximately 1 in 10 babies have IUGR and therefore an increased risk of neurological deficiencies, congenital malformations, meconium aspiration, hypoglycemia, hypocalcemia, and respiratory distress syndrome (RDS). IUGR may be due to chromosomal abnormalities; congenital infections; poor maternal health; the mother’s nutritional status and socioeconomic level; her use of cigarettes, alcohol; placental insufficiency; and multiple births (e.g., twins, triplets). Fetuses that weigh less than 500 g seldom survive. Page 4 of 4