Fertilization, Implantation & Folding PDF

PMS Block Embryology FERTILIZATION &Cleavage By Dr Haidy refaat Department of human Anatomy and Embryology Faculty of Medicine Assiut University  FERTILIZATION Definition: Fertiliza...

PMS Block Embryology FERTILIZATION &Cleavage By Dr Haidy refaat Department of human Anatomy and Embryology Faculty of Medicine Assiut University  FERTILIZATION Definition: Fertilization is fusion of a sperm and an ovum to produce a zygote. Of the 300-500 million sperms deposited in the vagina, only 300-500 sperms reach the fertilization site in the Fallopian tube. Only one sperm is needed for fertilization, and the others aid the fertilizing sperm in penetrating the barriers protecting the female gamete. Fertilization is a complex sequence of events that begins with contact between a sperm and an oocyte, and ends with intermingling of maternal and paternal chromosomes at metaphase of the first mitotic division of the zygote. Site: The ampulla (widest and longest part) of the uterine tube. Duration: Fertilization takes 24 hours. Chemical signals (attractants) secreted by the ovum and follicular cells guide the sperm to the ovum (sperm chemotaxis). Diagram of phases of fertilization First phase 1-Capacitation Seminal plasma proteins and a glycoprotein coat are removed from surface of sperm. 2-Acrosome reaction Capacitated sperms develop perforations in the acrosome. Acrosome reaction is associated with the release of enzymes. 3-Passage of sperm through corona radiata Second phase 4-Penetration of zona pellucida Release of acrosome enzymes cause lysis of the zona pellucida, allowing sperm to penetrate the zona. 5-Zona reaction Once sperm penetrates ZP, alteration in its structure and composition of (zona reaction) makes zona impermeable to other sperms. Phases of fertilization Third phase 6-Fusion of oocyte and sperm plasma membranes 7-Completion of the second meiotic division Penetration of oocyte by a sperm activates oocyte to complete the second meiosis forming a mature oocyte and a second polar body. 8-Formation of male & female pronucleus 9-Formation of the zygote Male and female pronuclei loose their nuclear membrane and fuse into a single diploid aggregation of chromosomes, zygote. 10-Preparation for cleavage of the zygote During growth of male and female pronuclei, they replicate their DNA.. chromosomes become arranged on a cleavage spindle in preparation of normal mitotic division (two cell stage). Results of fertilization 1-Stimulation of the oocyte to complete the second meiotic division. 2-Restoration of the diploid number of chromosomes, half from the father and half from the mother. Hence, the zygote contains a new combination of chromosomes different from both parents. 3-Determination of sex of the new individual, an X-bearing sperm produces a female embryo and a Y-bearing sperm produces a male embryo. 4-Initiation of cleavage: sperm carries activating factor that after fusion of the pronuclei stimulates cellular events associated with early embryogenesis. Without fertilization the oocyte degenerates 24 hours after ovulation.  EARLY EMBRYONIC DEVELOPMENT Cleavage (segmentation) of Zygote Definition: Cleavage or segmentation is rapid and repeated mitotic divisions of the zygote in order to increase the number of embryonic cells (blastomeres). Site: cleavage occurs as the zygote travels along the fallopian tube toward the uterus. Duration and steps: 30 hours after fertilization the zygote divides into 2-cell stage. 4-cell stage is reached by 40 hours and 16-cell stage (morula) is reached by 72 hours. It is noticed that by each cell division blastomeres increase in number but their sizes are reduced. Compaction: after the 8-cell stage, blastomeres are tightly aligned to form compact ball of cells. Blastocyst Formation The spherical morula (32 cells) enters the uterine cavity on day 4 after fertilization. Secretions from uterine glands diffuse through zona pellucida between its cells to form fluid space called blastocele. As fluid increases, it separates the blastomeres into two parts: 1. A thin outer layer – trophoblast (trophe=nutrition) – which gives rise to the embryonic part of the placenta. 2. A group of centrally located blastomeres – the inner cell mass – gives rise to the embryo. During this stage the conceptus is called blastocyst or blastula. Balstocyst formatiom  PMS Block Embryology IMPLANTATION BILAMINAR EMBRYO TRIAMINAR EMBRYO FOLDING By Dr Haidy refaat Department of human Anatomy and Embryology Faculty of Medicine Assiut University Balstocyst formatiom IMPLANTATION Definition: Implantation is embedding of the blastocyst in the endometrium. Proper site of implantation is near the midline of the upper part of the posterior wall of the uterus. Duration: from day 6 to day 12 after fertilization. As implantation proceeds, morphological changes occur in the embryoblast that produce bilaminar embryonic disc composed of epiblast and hypoblast. Steps of implantation: About day 6 after fertilization, the blastocyst attaches to the endometrial epithelium by its embryonic pole. As soon as it attaches, the trophoblast proliferates and differentiates into two layers: 1. -an inner cellular layer of cytotrophoblast. 2. -an outer syncytiotrophoblast; of multinucleated protoplasmic mass. At the embryonic pole syncytiotrophoblast show finger-like processes that expand to invade the endometrium. Clinical notes Syncytiotrophoblast secretes human chorionic gonadotrophins. hCG maintains the hormonal activity of corpus luteum up to the middle of pregnancy and forms the basis of pregnancy test as early as the end of the second week. Inhibition of implantation: Implantation can be inhibited by: a) Adminstration of large doses of estrgen b) Abortion pill. c) IUD causes local inflammation which interferes with implantation. Abnormal implantation a) Failure of implantation occurs in 25% of cases due to: genetic disorder, poorly developed endometrium or inadequate hormones by corpus luteum. b) Ectopic pregnancy is implantation outside the uterus. -In 95% of cases implantation occurs in the fallopian tube; Other rare sites of ectopic pregnancies are: ovary, abdomen, and cervix. Ectopic pregnancy  Bilaminar Germ Disc (Second Week of Development) At the 8th day cells of the inner cells mass differentiate into two layers: a) Epiblast: a layer of highly columnar cells. b) Hypoblast: a layer of small cuboidal cells adjacent to the blastocele. Cells of each germ layer form a flat disc and together are known as the bilaminar germ disc. At the same time a cavity appears within the epiblast known as the amniotic cavity. Epiblast cells which line the amniotic cavity are called amnioblasts. At the 9th day flattened cells from hypoblast form a primitive yolk sac. Implantation and early embryonic formation  At the 11th-12th day a new population of cells derived from the wall of the yolk sac form loose connective tissue extraembryonic (primary) mesoderm. Soon large cavities develop in the extraembryonic mesoderm and when they fuse a new space known as extraembryonic celom (chorionic cavity) is formed. The space surrounds the amniotic cavity and primitive yolk sac except when the germ disc is connected to the trophoblast by connecting stalk (future umbilical cord). The extraembryonic celom separates the extraembryonic mesoderm into two layers; outer somatic mesoderm and inner splanchnic mesoderm. At the 13th day the trophoblast is characterized by the appearance of villous structures. known as primary chorionic villi. By two-week embryo, the extraembryonic celom expands and forms the chorionic cavity. The trophoblast and its lining of somatic mesoderm are together known as the chorion (chorionic plate). The whole vesicle of the two-week embryo, about 2 mm, is known as the chorionic vesicle. The germ (embryonic) disc is 0.2mm long and egg-shaped.  TRIAMINAR EMBRYO Rapid development of the embryonic disc during the 3rd week is characterized by: 1) Formation of three germ layers: ectoderm, mesoderm, endoderm. This is termed gastrulation. Embryo is named gastrula, becomes pear shaped. From these 3 germ layers all tissues and organs of the body differentiate. 2) Formation of notochord. 3) Development of the chorionic villi. By end of 3rd week the embryo is 3mm long. Notice 2-week embryo is 0.2 mm, it means in the 3rd week, embryo increases 15 times in length. 1)Formation of three germ layers Gastrulation is the process by which 3 germ layers are formed. It begins with formation of primitive streak (day 14) as a linear opacity in midline of dorsal aspect of embryo. Cranial end of primitive streak forms a node, primitive node. A primitive groove develops in primitive streak.  Gastrulation By end of week-3, It is possible to identify embryo’s cranial and caudal ends, its dorsal and ventral surfaces and its right and left sides. Cells of the epiblast migrate in the direction of the primitive streak, become flask-shaped, detach from epiblast and slip beneath it. Some cells displace hypoblast cells creating definitive embryonic endoderm on roof of yolk sac. Other cells leave deep surface of primitive streak and come to lie between epiblast and endoderm to form intrarmbryonic mesoderm. Mesodermal cells spread cranially and laterally to fill gap between ectoderm and endoderm. Remaining cells of epiblast form embryonic ectoderm. Cross section of a tri-laminar 3-week embryo, showing divisions of intraembryonic mesoderm Fate of the primitive streak The primitive streak forms secondary mesoderm until early in week-4 when production of mesoderm slows down. The primitive streak degenerates by the end of week 4. Clinical Notes 1-Remnants of primitive streak may persist and give rise to a tumor containing various types of tissue elements of the Sacrococcygeal teratoma three germ layers in incomplete stages of differentiation, known as sacrococcygeal teratoma. 2-Gastrulation may be impaired by genetic and teratogenic factors. Sirenomelia, is a syndrome in which there is insufficient mesoderm formed in caudal region of the embryo with hypoplasia of lower limbs, vertebral anomalies, renal agenesis, imperforte anus and genital anomalies. 2) Formation of Notochord On day 17, Some cells in primitive node move forward in a cephalic direction until they reach the prechordal plate. Notochord extends from primitive node to prechordal plate. As primitive streak regresses the notochord is stretched caudally. Functions and Fate of notochord The notochord degenerates but it persists as the nucleus pulposus of intervertebral discs. Notochord forms axial part supporting embryo. It induces development of the neural tube.  Chordoma Anomalies of the notochord Chordomas is remnants of notochord which may give benign or malignant tumors. chordoma 3) Development of Chorionic Villi Chorionic villi develop in three stages; primary, secondary and tertiary. 1. Primary chorionic villi appear by end of week 2 as trophoblastic projections. 2. Early in week 3, mesenchyme grows into the primary villi to become secondary chorionic villi. 3. Mesenchymal cells in the villi differentiate into capillaries and blood cells. Villi are now called tertiary chorionic villi. Capillaries in villi fuse to form vascular networks, which connect to umbilical vessels to embryo’s heart. By end of week 3, embryonic blood flows in the villi. Oxygen and nutrients in maternal blood in intervillous spaces diffuse through walls of villi and enter the embryo’s blood. Carbon dioxide and waste products diffuse back from embryonic capillaries through walls of the villi into maternal blood. Primary, secondary and tertiary chorionic villi. It is through walls of free villi that the main exchange between blood of the mother and embryo takes place. Folding of embryo and its results Early in the 4th week the embryo undergoes folding. Cephalocaudal folding is caused by the rapid longitudinal growth of the neural tube. Lateral folding is produced by the rapidly growing somites. There are head fold, tail fold and two lateral folds. Folding of embryo in week 4 Results of folding 1-Embryo attains a round body form. 2-The brain is pulled forward and becomes the most cranial organ. 3-Septum transversum (future diaphragm), heart, pericardium and oropharyngeal membrane that were cranial to the brain move to a ventral and caudal position. Pericardium becomes ventral to the heart. Stomodeum lies between the brain and the heart. 4-Endoderm of yolk sac is incorporated in the head fold to form foregut, and in the tail fold to form hindgut. Midgut communicates with the yolk sac by the vitelline duct. 5-The connecting stalk shifts from a caudal position to a ventral position and merges with the vitelline duct to form umbilical cord. 6-The amniotic cavity expands on expense of yolk sac, and its attachment to ventral surface is reduced at the umbilical region.  PMS Block Embryology EARLY TISSUE AND ORGAN DIFFERENTIATION By Dr Haidy refaat Department of human Anatomy and Embryology Faculty of Medicine Assiut University Derivatives of Ectoderm Neurulation is formation, separation and closure of the neural tube. It starts during Neurulation week-3 and is completed by end of week-4. The neural plate appears as thickening of ectoderm cranial to primitive node. By end of week-3,. Neural folds approach each other in midline, fuse to form the neural tube. Fusion is accompanied by separation from surface ectoderm.. Formation of neural tube and somites  Neuroectodermal cells at lateral borders of neural folds dissociate and form paired neural crests. Neural crest cells migrate and differentiate to other types of cells. Derivatives of neural crest cells: 1-spinal and autonomic ganglia, and ganglia of cranial nerves V,VII,IX,X. 2-Schwann (neurolemma) cells. 3-Meninges (pia and arachnoid). 4-Melanocytes. 5-Suprarenal medulla. 6-Bones and connective tissues of head&neck. 8-Enamel of teeth. Summary of derivatives of ectoderm Ectoderm germ layer gives rise to structures that protect and maintain contact of the embryo with the outside: 1-Nervous system. 2-Sensory epithelium of eye, ear and nose. 3-Epidermis of skin including hairs, nails, sweat glands and mammary glands. 4-Enamel of teeth. 6-Pituitary gland. Clinical Note Anencephaly (partial absence of the brain), is the most common and most severe neural tube defect, due to failure of closure of neural tube. spina bifida is a condition that affects the spine and is usually apparent at birth due to neural tube defect (NTD Folic acid supplementation to pregnant mother is a preventive measure.  Derivatives of Mesoderm By day 17, mesoderm close to the midline on each side of the notochord forms a thick longitudinal column of paraxial mesoderm. This is followed by intermediate mesoderm and lateral mesoderm. Cavities appear in the lateral mesoderm and fuse to form intraembryonic coelomic cavity. Intraembryonic coelom divides lateral cell mass into two layers: a) Somatic or parietal outer layer. b) Splanchnic or visceral inner layer. Somatic mesoderm and the overlying ectoderm form the body wall, splanchnic mesoderm and the underlying endoderm form the gut. Derivatives of mesoderm Paraaxial mesoderm Paraxial mesoderm becomes organized into segments or somites. until the end of the 5th week, 44 pairs of somites are recognized. Cells of the ventromedial walls of somites form sclerotomes which shift to surround the notochord and spinal cord to form the vertebral column. The dorsolateral walls of somites form dermatomyotomes which constitute myotomes and dermatomes. myotomes provide muscules of axial skeleton. Dermatome forms dermis and subcutaneous tissue of skin. Intermediate Mesoderm develop into the urinary and genital systems. Lateral Mesoderm Parietal (somatic) mesoderm together with overlying ectoderm form the lateral and ventral body walls. Visceral (splanchnic) mesoderm and underlying endoderm will form the wall of the gut Summary of derivatives **** of mesoderm Mesoderm germ layer is the middle supportive and connective layer and gives rise to: 1-Connective tissues, cartilages, bones and muscles. 2-Heart, blood vessels, blood cells and the spleen. 3-Serous membranes; pericardium, pleura and peritoneum. 4-Dermis of skin. 5-Suprarenal cortex. 6-Urogenital system. Derivatives of endoderm The endoderm germ layer, the inner lining and nutritive layer, gives rise to: 1-Epithelial lining of the gut and respiratory tract. 2-Parynchyma of thyroid, parathyroid, liver and pancreas. 3-Stroma of tonsils and thymus. 4-Epithelial lining of urinary bladder and urethra. 5-Epithelial lining of tympanic cavity and auditory tube.