Implantation & Bilaminar Germ Disk Formation PDF

IMPLANTATION & BILAMINAR GERM DISK FORMATION Gizem SÖYLER, PhD Near East University Faculty of Medicine Department of Histology & Embryology In The Last Episode Expanded Blastocyst & Hatching  As implantation of the blastocyst occurs, morphologic changes in the embryoblast produce a bilaminar...

IMPLANTATION & BILAMINAR GERM DISK FORMATION Gizem SÖYLER, PhD Near East University Faculty of Medicine Department of Histology & Embryology In The Last Episode Expanded Blastocyst & Hatching  As implantation of the blastocyst occurs, morphologic changes in the embryoblast produce a bilaminar embryonic disc composed of epiblast and hypoblast. The embryonic disc gives rise to the germ layers that form all the tissues and organs of the embryo. Extraembryonic structures forming during the second week are the amniotic cavity, amnion, umbilical vesicle connecting stalk, and chorionic sac. Implantation – Day 6-8 Approximately 6 days after fertilization (around day 20 of a typical 28- day menstrual cycle), the blastocyst attaches to the endometrial epithelium, usually near the embryonic pole. At the eighth day of development, the blastocyst is partially embedded in the endometrial stroma. In the area over the embryoblast, the trophoblast has differentiated into two layers: 1. an inner layer of mononucleated cells, the cytotrophoblast, 2. an outer multinucleated zone without distinct cell boundaries, the syncytiotrophoblast.  Mitotic figures are found in the cytotrophoblast but not in the syncytiotrophoblast. Thus, cells in the cytotrophoblast divide and migrate into the syncytiotrophoblast, where they fuse and lose their individual cell membranes. The syncytiotrophoblast, a multinucleated mass without distinct cell boundaries, extends finger-like processes through the endometrial epithelium and produces enzymes that further erode maternal tissues, allowing the blastocyst to embed itself more deeply into the endometrium.  Cells of the inner cell mass or embryoblast also differentiate into two layers: 1. a layer of small cuboidal cells adjacent to the blastocyst cavity, known as the hypoblast layer, 2. a layer of high columnar cells adjacent to the amniotic cavity, the epiblast layer. Together, the layers form a flat disc. At the same time, a small cavity appears within the epiblast. This cavity enlarges to become the amniotic cavity. Epiblast cells adjacent to the cytotrophoblast are called amnioblasts; together with the rest of the epiblast, they line the amniotic cavity. The endometrial stroma adjacent to the implantation site is edematous and highly vascular. The large, tortuous glands secrete abundant glycogen and mucus. Day 9 The blastocyst is more deeply embedded in the endometrium, and the penetration defect in the surface epithelium is closed by a fibrin coagulum. The trophoblast shows considerable progress in development, particularly at the embryonic pole, where vacuoles appear in the syncytium.  When these vacuoles fuse, they form large lacunae, and this phase of trophoblast development is thus known as the lacunar stage. At the abembryonic pole, meanwhile, flattened cells probably originating from the hypoblast form a thin membrane, the exocoelomic (Heuser) membrane that lines the inner surface of the cytotrophoblast. This membrane, together with the hypoblast, forms the lining of the exocoelomic cavity, or primitive yolk sac.  Day 11-12 By the 11th to the 12th day of development, the blastocyst is completely embedded in the endometrial stroma. Initially, there is a surface defect in the endometrial epithelium that is soon closed by a closing plug of a fibrin coagulum of blood. By day 12, an almost completely regenerated uterine epithelium covers the closing plug. The blastocyst now produces a slight protrusion into the lumen of the uterus.  Concurrently, cells of the syncytiotrophoblast penetrate deeper into the stroma and erode the endothelial lining of the maternal capillaries. These capillaries, which are congested and dilated, are known as sinusoids. The syncytial lacunae become continuous with the sinusoids, and maternal blood enters the lacunar system. As the trophoblast continues to erode more and more sinusoids, maternal blood begins to flow through the trophoblastic system, establishing the uteroplacental circulation.  This early circulation allows for the exchange of oxygen and nutrients between the mother and embryo. Oxygenated blood enters the lacunae from spiral endometrial arteries, while poorly oxygenated blood is removed through endometrial veins. This circulation system ensures that the embryo receives the necessary oxygen and nutrients for its development.  In the meantime, a new population of cells appears between the inner surface of the cytotrophoblast and the outer surface of the exocoelomic cavity. These cells, derived from yolk sac cells, form a fine, loose connective tissue, the extraembryonic mesoderm, which eventually fills all of the space between the trophoblast externally and the amnion and exocoelomic membrane internally. Soon, large cavities develop in the extraembryonic mesoderm, and when these become confluent, they form a new space known as the extraembryonic cavity, or chorionic cavity. This space surrounds the primitive yolk sac and amniotic cavity, except where the germ disc is connected to the trophoblast by the connecting stalk.  The extraembryonic mesoderm lining the cytotrophoblast and amnion is called the extraembryonic somatic mesoderm; the lining covering the yolk sac is known as the extraembryonic splanchnic mesoderm. Growth of the bilaminar disc is relatively slow compared with that of the trophoblast; consequently, the disc remains very small (0.1 to 0.2 mm). Cells of the endometrium, meanwhile, become polyhedral and loaded with glycogen and lipids; intercellular spaces are filled with extravasate, and the tissue is edematous. These changes, known as the decidua reaction, at first, are confined to the area immediately surrounding the implantation site but soon occur throughout the endometrium. Decidualization The connective tissue cells around the implantation site accumulate glycogen and lipids and assume a polyhedral (many-sided) appearance. Some of these cells, decidual cells, degenerate adjacent to the penetrating syncytiotrophoblast. The decidual reaction provides an immuneprotective environment for the development of the embryo. The decidual reaction involves: 1. The production of immunosuppressive substances (mainly prostaglandins) by decidual cells to inhibit the activation of natural killer cells at the implantation site. 2. Infiltrating leukocytes in the endometrial stroma that secrete interleukin-2 to prevent maternal tissue rejection of the implanting embryo. Syncytiotrophoblast cells do not express major histocompatibility complex class II. Therefore, the syncytiotrophoblast cannot present antigens to maternal CD4+ T cells. Day 13 By the 13th day of development, the surface defect in the endometrium has usually healed. Occasionally, however, bleeding occurs at the implantation site as a result of increased blood flow into the lacunar spaces. Because this bleeding occurs near the 28th day of the menstrual cycle, it may be confused with normal menstrual bleeding and, therefore, may cause inaccuracy in determining the expected delivery date. The trophoblast is characterized by villous structures. Cells of the cytotrophoblast proliferate locally and penetrate into the syncytiotrophoblast, forming cellular columns surrounded by syncytium. Cellular columns with the syncytial covering are known as primary villi.  In the meantime, the hypoblast produces additional cells that migrate along the inside of the exocoelomic membrane. These cells proliferate and gradually form a new cavity within the exocoelomic cavity. This new cavity is known as the secondary yolk sac or definitive yolk sac. This yolk sac is much smaller than the original exocoelomic cavity, or primitive yolk sac.  During its formation, large portions of the exocoelomic cavity are pinched off. These portions are represented by exocoelomic cysts, which are often found in the extraembryonic coelom or chorionic cavity. Meanwhile, the extraembryonic coelome expands and forms a large cavity, the chorionic cavity. The extraembryonic mesoderm lining the inside of the cytotrophoblast is then known as the chorionic plate. The only place where extraembryonic mesoderm traverses the chorionic cavity is in the connecting stalk. With development of blood vessels, the stalk becomes the umbilical cord.  The syncytiotrophoblast produces a glycoprotein hormone, hCG, which enters the maternal blood via isolated cavities (lacunae) in the syncytiotrophoblast; hCG maintains the hormonal activity of the corpus luteum in the ovary during pregnancy. The corpus luteum is an endocrine glandular structure that secretes estrogen and progesterone to maintain pregnancy. Enough hCG is produced by the syncytiotrophoblast at the end of the second week to give a positive pregnancy test, even though the woman is probably unaware that she may be pregnant.  https://www.youtube.com/watch?v=bIdJOiXpp9g  The second week of development is known as the week of 2’s: 1. The trophoblast differentiates into two layers: the cytotrophoblast and syncytiotrophoblast. 2. The embryoblast forms two layers: the epiblast and hypoblast. 3. The extraembryonic mesoderm splits into two layers: the somatic and splanchnic layers. 4. Two cavities form: the amniotic and yolk sac cavities. Ectopic Pregnancies Ectopic pregnancies occur when a blastocyst implants outside the uterus, with 95% to 98% occurring in the uterine tubes, most often in the ampulla and isthmus. Tubal pregnancies are the leading cause of maternal deaths during the first trimester. Symptoms Women with tubal pregnancies exhibit typical pregnancy symptoms along with abdominal pain, tenderness, abnormal bleeding, and sometimes peritonitis. Pain may mimic appendicitis if the pregnancy is in the right uterine tube. These pregnancies produce β-human chorionic gonadotropin at a slower rate, leading to possible false-negative results in early tests. Transvaginal ultrasonography is crucial for early detection. Causes Factors delaying or preventing the zygote's transport into the uterus, such as mucosal adhesions or scarring from pelvic inflammatory disease, often cause tubal pregnancies. These pregnancies typically result in the rupture of the uterine tube and hemorrhage within the first 8 weeks, necessitating surgical removal of the affected tube and conceptus. Implantation Sites Can Be Isthmus of the Uterine Tube: Narrow and unexpandable, often rupturing early with extensive bleeding. Intramural Uterine Tube: May develop beyond 8 weeks before rupture, causing significant bleeding. Ampulla or Fimbriae of the Uterine Tube: Can be expelled into the peritoneal cavity, sometimes leading to abdominal pregnancies, which may go to full term but involve high maternal risk from hemorrhage. Abdominal Pregnancies: High risk of maternal death; rare instances of the fetus surviving, or forming a "stone fetus" (lithopedion) if undetected. Heterotopic Pregnancies: Rare simultaneous intrauterine and ectopic pregnancies, more common with assisted reproductive technologies. Cervical Implantations: Rare, often leading to heavy bleeding and requiring surgical interventions like hysterectomy.