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Embryology 8 In this lecture we will talk about the second week of development of the blastocyst. The most important event in the second week is forming the bilaminar germ disc which consists of the primary ectoderm from epiblast and the primary endoderm from hypoblast. Note: when we talk about the development of the embryo in any day we should mention two things: 1-the developments in the blastocyst that happens to the embryo. 2-the developments in the endometrium. we had learned that in the seventh day the blastocyst implants superficially in the endometrium (in the tenth day it become completely implanted )also the trophoblast had turned to cytotrophoblast and syncytiotrophoblast and the blastocyst cavity still existing, but also the amniotic cavity formed above the epiblast. Embryology 8 The eighth day Blastocyst development Blastocyst is partially embedded in the endometrial stroma (partial implantation). In the area over the embryoblast, the trophoblast has differentiated into two layers: 1-cytotrophoblast (which have cell membranes "obvious boundary " ,mononucleated and divide by mitotic division). 2-syncytiotrophoblast (which multinucleated zone without distinct cell boundaries and no divisions) 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 secrete HCG hormone that used in the pregnancy test the implantation took place in the superficial layer (surface epithelium)by penetration of the embryo in the seventh day so the surface epithelium contains an opening that will be closed by fibrin clot at the end of implantation then the surface epithelium regenerates and forms complete surface . the part of the embryo that penetrates the endometrium called embryonic pole and the opposite pole called abembryonic pole. By the end of the thirteenth and the fourteenth days (the second week) the whole embryo has become inside the endometrium and the changes surround all its parts. Embryology 8 The changes in the endometrium in the 8th day: The small blood vessels dilate and encourage also the glands of the uterine to become fully secretive and to secrete the glycogen and other proteins to nourish the embryo. The endometrial stroma adjacent to the implantation site is edematous and highly vascular. The large, tortuous glands secrete abundant glycogen and mucus. Cells of the inner cell mass or embryoblast also differentiate into two layer (a) a layer of small cuboidal cells adjacent to the blastocyst cavity, known as the hypoblast layer, (b) a layer of high columnar cells adjacent to the amniotic cavity, the epiblast layer that differentiate to the ectoderm layer in the future. The three germ layers of the embryo that will form in the future are: 1-the ectoderm (external layer) 2-the mesoderm (middle layer) 3-the endoderm (internal layer) And these three layers will differentiate to form the all different organs of the body. Like the connective tissues (blood, lymph, bones and cartilage) which originate from the mesoderm layer. The epiblast also called primary ectoderm and the hypoblast called primary endoderm these two layers form the bilaminar germ disc, notice that the primary mesoderm layer has not formed yet. At the same time, a small cavity appears within or above the epiblast. This cavity enlarges to become the amniotic cavity. Epiblast (columnar cells) cells adjacent to the cytotrophoblast are called amnioblasts(flattened cells); together amnioblast with the rest of the epiblast, they line the amniotic cavity and this amniotic cavity formed inside the epiblast and in the future it will enlarge and contain the amniotic fluid that surrounds the embryo completely with the amniotic membrane (from the amnioblast cells). Embryology 8 The Ninth day Blastocyst Development The amniotic cavity gradually enlarges and the amnioblast cells with epiblast become apparent. The hypoblast cells proliferate especially at the edges and continue downwards as primary endodermal cells. The blastocyst cavity turns to exocoelomic cavity, or primitive (primary) yolk sac and its function is nourishment to the embryo. It acquired this name because its lined by exocoelomic (Heuser's) membrane which proliferated "the membrane" from the hypoblast cells. So the lining epithelium of the exocoelomic cavity is the hypoblast cells from above and the exocoelomic (Heuser's) membrane from the sides. At the place of penetration, a fibrin coagulum has formed and the whole embryo is now inside the endometrium, so the implantation occurred fully either by the end of the ninth day or the beginning of the tenth day. The epithelial surface of the endometrium enters mitotic division to make fully healing in the place of implantation and the cytotrophoblasts all around the blastocyst enter mitotic division and form syncytiotrophoblast even at the abembryonic pole, as well as trophoblastic lacunae(called like this because the syncytiotrophoblast originate from trophoblast) formed within syncytiotrophoblast ,these lacunae will fuse with the uterine blood vessels to form the uteroplacental circulation, note that in the future the syncytiotrophoblast will grow up to form placenta. Embryology 8 The changes in the endometrium in the 9th day: The epithelial surface of the endometrium enters mitotic division to make fully healing in the place of implantation and the blood vessels become dilated , enlarged and near to synsytiotrophpblast. 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(synsytiotrophpblast). 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’s) 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. The tenth day The blastocyst is completely implanted. The endometrium divides to fully close implantation place with epithelium. The eleventh and the twelfth days The extraembryonic coelom (also called primary mesoderm) forms in the 11th day and it's called extra embryonic because it is out of the bilaminar germ disc. This extraembryonic ceolom is extraembryonic mesoderm and the Heuser's membrane will be replaced by primary endoderm cells extraembryonic endoderm and the primary yolk sac will turn to a secondary yolk sac which smaller in the size. Embryology 8 The changes in the endometrium in the 11th & 12th days: Trophoblastic lacunae will be formed at abembryonic pole and the syncytiotrophoblast will penetrate large area of the endometrium ,also the dilated and encouraged blood vessels grow up to maternal sinusoids at the embryonic pole Sinusoids: large spaces filled with maternal bloods in the endometrium These sinusoids in the maternal side ,but in the embryonic side the trophblastic lacunae enlarge and do communication with sinusoids in the 12th day This communication called uteroplacental circulation functions as a nourishment. By the 11th to 12th day of development, the blastocyst is completely embedded in the endometrial stroma and the surface epithelium almost entirely covers the original defect in the uterine wall The blastocyst now produces a slight protrusion into the lumen of the uterus. The trophoblast is characterized by lacunar spaces in the syncytium that form an intercommunicating network. This network is particularly evident at the embryonic pole; at the abembryonic pole, the trophoblast still consists mainly of cytotrophoblastic cells 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. In the meantime, a new population of cells appears between the inner surface of the cytotrophoblast and the outer surface of the exocoelomic cavity.here there is very important event including the proliferating of the cells. Embryology 8 These cells, derived from yolk sac cells, form a fine, loose connective tissue called, the extraembryonic mesoderm, which eventually fills all of the space between the cytotrophoblast 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 coelom, 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 also,it surrounds the bilaminar germ disc. The connecting stalk is the part that will form in the future the umbilical cord Note Nobody exactly know the origin of the extraembryonic mesoderm but the some supposed it has come from the edges of the bilaminar germ disc but actually there is genome box in the embryonic cells programmed by the time so in the 12th or 13th day it is translated and form the extraembryonic mesoderm layer The extraembryonic mesoderm lining the cytotrophoblast and amnion is called the extraembryonic somatopleuric mesoderm the lining covering the yolk sac is known as the extraembryonic splanchnopleuric )(حشويةmesoderm Growth of the bilaminar disc is relatively slow compared with that of the trophoblast the disc remains very small (0.1–0.2 mm). Embryology 8 Cells of the endometrium, meanwhile, become polyhedral and loaded with glycogen and lipids; intercellular spaces are filled with extravasate, and the tissue is edematous.(the endometrium becomes edematous by the fluids ,glycogen and other proteins) These changes, known as the decidua reaction (the changes of the endometrium), at first are confined to the area immediately surrounding the implantation site but soon occur throughout the endometrium. The decidua is three types: 1- basalis that forms placenta and it's the most important one. 2-capsularis 3-parietalis **Pleural is the adjective of pleura which surround the organs like the parietal(somatic) and visceral(splanchnic) pleura of the lungs. The thirteenth day: Blastocyst development: The connecting stalk is the only part of the embryo out the chorion ,it's at the side of the tail of the embryo. The extraembryonic coelom (chorionic cavity) enlarges and the primary yolk sac decreases in size forming secondary yolk sac. Embryology 8 The Heuser's membrane turns to extraembryonic endoderm lines the secondary yolk sac,peripherally to the extraembryonic endoderm is extraembryonic splanchnopleuric mesoderm The extracoelomic cyst has no importance it just produced by changing the yolk sac from primary to secondary The cytotrophoblast makes primary villi which is protrusion the cytotrophoblast through the synsytium at the embryonic pole then secondary villi formed and protrude the synsytium in the endometrium also there is tertiary villi and finally it form the placenta. The changes in the endometrium in the 13th day: It become edematous and filled with lipids, glycogen and proteins The trophoblastic lacunae began in the embryonic pole and it will extend to reach the abembryonic pole. Decidual reaction still exists. 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, cause inaccuracy in determining the expected delivery date(some pregnant ladies have in the 28th day of menstrual cycle (the thirteenth day of pregnancy)have bleeding as the menstrual cycle caused by the bulky amount of blood in lacunar spaces that results in miscalculation the 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 (extraembryonic endoderm cells)that migrate along the inside of the exocoelomic membrane These cells proliferate and gradually form a new cavity within the exocoelomic cavity. Embryology 8 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. The beginning of the fourteenth day: Meanwhile, the extraembryonic coelom 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 (including the cytotrophoblast and extraembryonic). 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. Pregnancy tests 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 radioimmunoassay, which serve as the basis for pregnancy testing. Abnormal implantation: Abnormal implantation sites sometimes occur even within the uterus. Occasionally the blastocyst implants close to the internal opening os (opening) of the cervix. the placenta bridges the opening (placenta previa) and causes severe, even lifethreatening bleeding in the second part of pregnancy and during delivery so the baby born by caesarean surgery. Embryology 8 Occasionally, implantation takes place outside the uterus, resulting in extrauterine pregnancy, or ectopic pregnancy. Ectopic pregnancies may occur at any place in the abdominal cavity, ovary, or uterine tube However, 95% of ectopic pregnancies occur in the uterine tube, and most of these are in the ampulla In the abdominal cavity, the blastocyst most frequently attaches itself to the peritoneal lining of the rectouterine cavity, or Douglas’ pouch (these cases is not important) Sometimes the blastocyst develops in the ovary proper, causing a primary ovarian pregnancy. In most ectopic pregnancies, the embryo dies about the second month of gestation, causing severe hemorrhaging and abdominal pain in the mother . hydatidiformmole Abnormal blastocysts are common. It is likely that most abnormal blastocysts would not have produced any sign of pregnancy because their trophoblast was so inferior that the corpus luteum could not have persisted. In some cases, however, the trophoblast develops and forms placental membranes, although little or no embryonic tissue is present. Such a condition is known as a hydatidiformmole. Moles secrete high levels of hCG and may produce benign or malignant (invasive mole, choriocarcinoma. Good luck Afnan Emad