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Volgograd state medical university Department of histology, embryology, cytology for the 1st course English medium students Volgograd, Volgograd, 2013 2013 1 Objectives: Objectives: 1. To describe development, structure and functions of placenta and umbilical cord. 2. To characterize the fetal membranes – chorion, chorion, amnion, yolk sac, allantois. allantois. 3. To evaluate the stages of the fetal period. 2 1 FUNCTIONS FUNCTIONS OF OF PLACENTA PLACENTA AND AND FETAL FETAL MEMBRANES: MEMBRANES: Before birth: Protection Nutrition Respiration Excretion Hormone production At birth: Placenta and fetal membranes separate from the fetus and are expelled from the uterus as afterbirth. 3 FULL-TERM FULL FULL-TERM PLACENTA PLACENTA Placenta is a fetomaternal organ with fetal and maternal portion. It permits the exchange of materials carried in the bloodstreams of the mother and embryo/fetus. The chorion, chorion, amnion, yolk sac and allantois constitute the fetal membranes. They develop from a zygote but do not form embryonic structures, except for portions of the yolk sac and allantois. allantois. 4 2 DEVELOPMENT DEVELOPMENT OF OF PLACENTA PLACENTA inner cell mass degenerating zona pellucida blastocyst cavity 44 days days trophoblast 55 days days The morula passes down the uterine tube, enters the uterus and fluid passes into the morula from the uterine cavity and collects between the cells. As the fluid increases, it separates these cells cells into two parts: an outer cell mass called trophoblast and the inner cell mass called embryoblast. embryoblast. Trophoblast is the 1st extraembryonic organ of the conceptus to be formed. It will give rise to chorion 5and placenta. Early stage of implantation (the 6th day). The trophoblast is attached to the endometrial epithelium at the embryonic pole of the blastocyst. blastocyst. On about 5th day zona pellucida disappears and the blastocyst 6 attaches to the maternal uterine epithelium on about 6th day. 3 IMPLANTATION IMPLANTATION In humans trophoblastic cells over the embryoblast pole begin to penetrate between the epithelial cells of the uterine mucosa 7 about the 6th day. Early Early Stage Stage of of Implantation Implantation (7th (7th day). day). As invasion of the trophoblast proceeds, two cell layer form in it: an inner cytotrophoblast (cellular) and an outer syncytiotrophoblast. syncytiotrophoblast. The fingerfinger-like processes of syncytiotrophoblast penetrate the endometrial epithelium, begin to destroy adjacent endometrial cells and invade endometrial stroma. stroma. By the end of the 1st week the blastocyst is superficially implanted in the endometrium. endometrium. 8 4 Week Week 2. 2. Day Day 8. 8. Size Size of of the the conceptus conceptus –– 0.1 0.1 mm mm At the 8th day the blastocyst is partially emembedded in the endometrial stroma. stroma. Small spaces appear between the cells of the inner cell mass (embryoblast), embryoblast), these spaces soon coalesce to form a slitslitlike amniotic cavity. 9 Blastocyst Blastocyst partially partially embedded embedded at at 8th 8th day, day, showing showing embryoblast embryoblast and and trophoblast trophoblast 10 As amniotic cavity forms, changes occur in the embryoblast resulting in the formation of the flattened, essentially circular, embryonic embryonic disk. 5 Human Human blastocyst. blastocyst. 88 days. days. Epiblast cells adjacent to the cytotrophoblast are called amnioblasts. amnioblasts. They comprise amnion. Together with the rest of the epiblast they line the amniotic cavity. The epiblast forms the floor of the amniotic cavity and is continuous peripherally 11 with the amnion. Amniotic Amniotic Cavity Cavity On day 8 of development, embryoblast differentiates into epiblast and hypoblast forming bilaminar germ disc. A small cavity appears within the epiblast. This cavity becomes amniotic cavity and the covering layer is amnion. Amniotic cavity contains amniotic fluid. 12 6 Human Human Blastocyst. . Blastocyst Blastocyst. Day 9. Day 9. Concurrently other cells probably originating from hypoblast form a thin exocelomic membrane (Heuser (Heuser’’s membrane) which encloses, together with the hypoblast, a cavity known as the primary primary 13 (primitive) yolk sac or exocoelomic cavity. Implanted . 10 blastocyst Implanted human human blastocyst. blastocyst. 10 days. days. 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 the yolk sac cells, form a fine fine loose 14 connective tissue, the extraembryonic mesoderm. 7 Implanted . 12 blastocyst Implanted human human blastocyst. blastocyst. 12 days. days. Extraembryonic mesoderm eventually fills all the space between the trophoblast externally and the amnion and exocoelomic membrane internally. Soon large cavities appear in it, and when these become confluent, they form a new space known as extraembryonic 15 coelom or chorionic cavity. Formation of primary or extraembyonic mesoderm between Heuser’ Heuser’s membrane and cytotrophoblast at 12th day. The extraembryonic mesoderm lining the cytotrophoblast and amnion is called the extraembryonic somatopleuric mesoderm; that covering 16 the yolk sac is called extraembryonic splanchnopleuric mesoderm. 8 Human Human embryo, embryo, 13 13 days days old. old. After implantation the endometrium transforms into decidua starting from implantation site. By the end of the 2nd week the endometrium is completely replaced by the decidua. decidua. The extraembryonic somatic mesoderm and the trophoblast together constitute the chorion. Extraembryonic mesoderm chorion. lining the inside of the trophoblast is known as chorionic plate. A small secondary yolk sac has formed inside the primitive 17 yolk sac as it is pinched off thus decreasing the primitive yolk sac. Human Human embryo, embryo, 14 days 14 days old. old. The definite yolk sac is much smaller than the primitive yolk sac or original exocoelomic cavity. 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 18 extraembryonic coelom or chorionic cavity. 9 Yolk Yolk Sac Sac The cavity related to the hypoblast is exocoelomic cavity which will be modified into primary yolk sac. Embryonic disc lies between amniotic cavity and primary yolk sac. ExtraExtra-embryonic mesoderm is developed from the lining cells of the yolk sac. Due to the development of extraembryonic coelom in the extraembryonic mesoderm, a large part of the primary yolk sac is pinched off forming the secondary yolk sac. 19 Human Embryo, 14 days old. Bilaminar germ disc lined with tall columnar ectoderm cells and cuboidal endoderm cells. It is connected to the overlying trophoblast by means 20 of connecting stalk. 10 Germ disk of a 1616-day embryo indicating the movement of surface epiblast cells through primitive streak and primitive node. 21 When the cloacal membrane appears, the posterior wall of the yolk sac forms a small finger-like outpouching or diverticulum from its caudal wall that extends into the connecting stalk. This diverticulum is called allantoenteric diverticulum or allantois (Greek “allantos”, “sausage”. In some lower vertebrates it serves as a reservoir for excretion products of the renal system. 17 days 22 11 Allantois Allantois It is formed about the 16th day of development when the yolk sac forms a small diverticulum that extends into the connecting stalk. In humans it remains rudimentary, but may be involved with early blood cells and blood vessels formation and is associated with development of the urinary bladder and may be involved in abnormalities of bladder development. As the bladder enlarges, the allantois becomes the urachus. 23 Extraembryonic Extraembryonic Membane Membane Formation Formation The trophoblast develops the two layers: outer syncytiotrophoblast and inner cytotrophoblast. cytotrophoblast. The epiblast cell mass becomes hollow to form a fluidfluid-filled primitive amniotic cavity. The hypoblast cells form a simple squamous primitive yolk sac. 24 12 A second wave of hypoblast cell migration displaces the primitive primitive yolk sac. Extraembryonic mesoderm coats the old blastocyst cavity to complete the extraembryonic membranes. The trophoblast is now the threethree-layered chorion. chorion. Mesoderm and endoderm (former epiblast cells) form the definite yolk sac. Mesoderm and ectoderm (former epiblast cells) form the definite amnion. 25 Chorion Chorion Extraembryonic coelom becomes expanded to form a chorionic cavity. The extraembryonic mesoderm lining cytotrophoblast is known as chorionic plate. the Connecting stalk is extraembryonic mesoderm. the formed by The placenta forms of chorion. chorion. The connecting stalk between embryo and placenta shifts to the tail end of the embryo to form the umbilical cord. 26 13 Blastocyst Blastocyst of of 14 days 14 days showing showing chorionic chorionic cavity cavity and and endoderm endoderm lined lined secondary secondary yolk yolk sac sac The trophoblast is characterized by villous structure. Cells of cytotrophoblast proliferate locally and penetrate into the syncytiotrophoblast, syncytiotrophoblast, forming cellular columns surrounded by syncytium. syncytium. Cellular columns with the syncytial covering are known as primary villi. villi. By the beginning of the 3rd week the trophoblast is characterized by 27 primary villi that consist of cytotrophoblastic core covered by a syncytional layer. The The Human Human Blastocyst, , Blastocyst Blastocyst, th 99th day. day. Bilaminar Bilaminar germ germ disk disk in in the the lacunar lacunar stage. stage. The trophoblast shows considerable progress in development, particularly at the embryonic pole, where vacuoles appear in the syncytium. syncytium. When these vacuoles fuse, they form large lacunae, and this phase of trophoblast development is known as the lacunar stage. The lacunar networks are the primodia of the intervillous spaces of 28 the placenta. 14 Implanted Implanted human human blastocyst. . blastocyst blastocyst. 10 10 days. days. Trophoblastic lacunae at the embryonic pole are in open connection with maternal sinusoids in the endometrial stroma. stroma. The endometrial capillaries around the implanted embryo become dilated to form sinusoids and some of them become eroded by syncytiotrophoblast. syncytiotrophoblast. Maternal blood now seeps into the lacunar networks and soon begins to flow slowly through the lacunar system, establishing a primitive uteroplacental circulation. As both arterial and venous vessels come into communication with 29 the syncytiotrophoblastic lacunae, blood circulation is established. DEVELOPMENT DEVELOPMENT OF OF THE THE FETAL FETAL MEMBRANES MEMBRANES During further development mesodermal cells penetrate in the core of the villi and grow toward endometrium. newly endometrium. The 30 formed villi are called secondary villi. villi. 15 By the end of the 3rd week these cells begin to differentiate into blood cells and small blood vessels, forming the villous capillary capillary system. These villi are known as tertiary or definite villi. villi. Capillaries in them make contact with the capillaries developing in the mesoderm mesoderm of the chorionic plate and in the connecting stalk. These vessels in turn establish contacts with the intraembryonic circulatory system, connecting future placenta and the embryo. Hence, when the heart begins to beat in the 4th week of development, the villous system is ready to supply the embryo with oxygen and nutrients. 44 weeks weeks Developme Developme nt nt of of the the Fetal Fetal Membranes Membranes 31 Development Development of of Chorion. Chorion. Meanwhile cytotrophoblastic cells in the villi penetrate progressively into the overlying syncytium until they reach the maternal endometrium. endometrium. Here they establish contact with similar extensions of neighboring villous stems, forming a thin outer 32 trophoblastic shell. 16 This shell gradually surrounds the trophoblast entirely and attaches the chorionic sac firmly to the maternal endometrial tissue. Tertiary and secondary villi give trophoblast a characteristic radial appearance. Intervillous spaces are lined with syncytium. Cytotrophoblastic cells surround the trophoblast entirely and are in direct contact with endometrium. The chorionic cavity meanwhile becomes larger and larger. By the 20th day embryo is attached to its trophoblastic shell by only a narrow connecting stalk. The connecting stalk later develops into umbilical cord. Presomite Presomite Embryo. Embryo. 20 days 33 By the beginning of the 2nd month the trophoblast is characterized by a great number of secondary and tertiary villi that give it a radial appearance. The villi are anchored in the mesoderm of the chorionic plate and are attached peripherally to the maternal decidua by way of outer cytotrophoblastic shell. At abembryonic pole the villi are few and poorly developed. End End of of the the nd 22nd month month 34 17 Fetomaternal Fetomaternal Junction Junction Fetal part of the placenta (villous chorion) chorion) is separated from the maternal part (decidua (decidua basalis) basalis) by the cytotrophoblastic shell. 35 36 18 FORMATION FORMATION OF OF DECIDUA DECIDUA th week 4th The term decidua (Latin “falling off” off”): is applied to the functional layer of gravid (pregnant) endometendometrium indicating that it is shed at parturition. Three regions of decidua are designated according to their relation to the implantation site: decidua basalis – the part underlying the conceptus and forming the maternal component of placenta; decidua capsularis – the superficial portion overlying the conceptus and decidua parietalis – the remaining uterine mucosa. Until the 8th week chorionic villi cover the entire surface of chorionic sac. 37 DEVELOPMENT DEVELOPMENT OF OF THE THE DECIDUA DECIDUA As the sac grows, the villi associated with the decidua capsularis become compressed and their blood supply is reduced. Subsequently, Subsequently, these villi degenerate, producing by the end of the 2nd month a bare area known as the chorion laeve (Latin “levis” levis”=smooth). As it occurs, the chorionic villi associated with the decidua basalis, basalis, rapidly increase in number, branch profusely and enlarge. This portion of the of the 38 chorionic sac, known as the chorion frondosum (Latin “frondosus” frondosus”=leafy, bushy), forms the fetal component of the placenta. 19 Decidua basalis consists of a compact layer of large decidual cells, with abundant amount of lipid and glycogen. With a growth of the chorionic vesicle, decidua capsularis becomes stretched and degenerates. End End of of the the nd nd 22 Month Month 39 Subsequently the chorion laeve comes into contact with the uterine wall (decidua (decidua parietalis) parietalis) on the opposite side of the uterus, and the two fuse obliterating the uterine lumen. 40 20 Formation Formation of of the the Amnio-Chorionic Amnio-Chorionic Membrane. Membrane. As amniotic sac enlarges faster than the chorionic sac, the amnion and smooth chorion fuse to form amnioamniochorionic membrane. This is the membrane that ruptures during labour. labour. 10 weeks 20 weeks 41 Decidua Decidua is a functional layer of the endometrium of a pregnant women, decidual cells contain glycogen and lipids, falls off after parturition has three regions: Decidua basalis - maternal part of placenta Decidua capsularis - overlying conceptus Decidua parietalis - remaining parts 42 21 Placenta Placenta is a fetomaternal organ, fetal portion develops frondosum of chorionic sac, from chorionic maternal portion develops from decidua basalis of gravid endometrium, endometrium, provides protection, nutrition, excretion, hormone production. respiration, 43 Full-term Full-term placenta: placenta: is a discoid with a diameter of 15 to 25 cm, 3 cm thick, weighs 500500-600 g, at birth it is torn from the uterus wall, approximately 30 minutes after birth of a child it is expelled from the uterus. 44 22 ПОСЛЕД ПОСЛЕД 45 Full-Term Full-Term Placenta Placenta The final shape of placenta is determined by the form of the persistent area of chorionic villi giving the placenta a discoid shape. As the villi erode the decidua basalis, they leave several wedgeshaped areas of decidual tissue called placental septa. These septa divide the fetal part of placenta into 10-38 irregular areas called cotyledons. 46 23 Each cotyledon consists of two or more main stem villi and their many branches. The fetal portion of the placenta (or villous chorion) is anchored to the maternal portion of the placenta (decidua basalis) by anchoring villi. Blood-filled intervillous spaces are derived from the lacunae developed in the syncitiotrophoblast during 2nd week. Development Development of of the the Placentic Placentic Chorionic Chorionic Villi Villi 47 Collectively the spaces form a large blood sinus, the intervillous space, which is bound by the chorionic plate and decidua basalis. 48 24 Chorion Chorion Formation of chorionic villi: villi: Primary villi - consist of cytotrophoblastic core covered by a syncytial layer. Secondary villi = primary villi with mesodermal core. Tertiary villi = secondary villi with capillaries. Stem villi – arise from chorionic frondosum and project into the intervillous space containing maternal blood. 49 Chorion Chorion Chorionic plate - is the part of the chorionic wall related to the placenta. Chorionic frondosum (villous chorion) chorion) is formed by the chorion related to the decidua basalis. basalis. Chorion leave (smooth chorion) chorion) is related to the decidua capsularis degenerate and become smooth. 50 25 PLACENTA PLACENTA The intervillous space is divided into compartments by the placental septa, but because the septa do not reach the chorionic plate, there is communication between the interintervillous spaces of different compartcompartments. ments. The intervilintervillous space is drained by endoendometrial veins which open over the entire surface of decidua basalis. basalis. 51 Intervillous Intervillous Space Space Derives from the lacunae that developed in the syncytotrophoblast, syncytotrophoblast, Contains maternal blood, Spiral endometrial arteries pour blood in these spaces, Blood from these endometrial veins, spaces is drained by Branch villi float in the intervillous spaces. 52 26 The chorionic plate is on the fetal surface of the placenta. Extending from it with placental branches of the umbilical vessels are stem villi that branch extensively to form the free villi, villi, where metabolic exchange occurs. The syntrophoblast is the outer layer of the villi except at the ends of the anchoring villi that connect the villous chorion to the decidua basalis. basalis. Here the cytotrophoblast layer extends through the syntrophoblast to form the cytotrophoblastic shell at the interface between fetal and maternal component of the placenta. Decidual spiral arteries open through this shell to directly bathe the chorionic villi in maternal blood. Placental Placental Structure Structure 53 PLACENTAL PLACENTAL CIRCULATION CIRCULATION Placenta essentially provides a large area where materials may be exchanged across the placental membrane interposed between the fetal and maternal circulation. From the maternal blood fetal blood acquires nutrients and oxygen. Waste products formed within the embryo are carried to the placenta and transferred to the maternal blood. Within the placenta, the maternal and fetal bloodstreams flow close to each other BUT THEY DO NOT NORMALLY MIX!!! 54 27 Placenta Placenta Maternal blood circulates through the intervillous space (C), bringing nutrients and other substances necessary for embryonic and fetal development, and taking away the waste products of fetal metabolism. A – villus D – anchoring villus G – decidua basalis H – glands 55 Placental Placental Membrane Membrane (( Barrier) Barrier) is interposed between fetal and maternal circulation. is formed by extraextra-fetal tissues until 20 weeks consists of four layers — a) Syncytotrophoblast b) Cytotrophoblast c) Connective tissue of villi d) Endothelium of fetal capillaries 56 28 Chorionic Chorionic Villi Villi Bathed by Bathed by Maternal Maternal Blood Blood As pregnancy advances the placental membrane (barrier) becomes progressively thinner and many capillaries come to lie very very close to the syncytiotrophoblast sharing basal lamina (B). Syncitial cell mass may become trophoblastic embolus (A). Towards the end of pregnancy fibrinoid material forms on the surface of peripheral trophoblast in the junctional zone (Rohr’ Langhans’ Rohr’s fibrinoid.), fibrinoid.), Langhans’ subchorionic fibrinoid, fibrinoid, and Nitabuch’ Nitabuch’s basal fibrinoid layer. 57The cytotrophoblast disappears. These changes result from aging. Collectively the spaces form a large blood sinus, the intervillous space, which is bound by the chorionic plate and decidua basalis. 58 29 59 CLINICAL CLINICAL CORRELATIONS CORRELATIONS Maternal antibodies (IgG (IgG class) are transported to fetal capillaries by syncitiotrophoblast pinocytosis, pinocytosis, providing passive immunity against diphteria, diphteria, smallpox, measles, etc, but not against chickenpox and wooping cough. Passive immunity is important because the fetus has little capacity to produce own antibodies until after birth. Fetal red blood cells invading the maternal blood stream (through (through small bleeds at the surface of the villi) villi) may elicit antibody response in the mother if fetus is RhRh-positive while mother is RhRh-negative. Maternal antibodies return to the fetus causing hemolytic disease disease of the newborn which may lead to the intrauterine death. Many viruses traverse the placenta without difficulty (rubella, cytomegalovirus, Coxsackie, variola, varicella, measles, variola, varicella, poliomyelitis) causing fetal infection resulting in death or malformations. Most drugs and drug metabolites traverse placenta easily causing damage (antibiotics, anticoagulants, anticonvulsants, antitumor agents). Maternal use of heroine and cocaine can cause habituation in the 60 fetus. 30 Newborn male infant with typically malformed limbs (meromelia) meromelia) caused by thalidomide 61 Hormone Hormone Production Production by by the the Placenta Placenta (Syntropoblast): (Syntropoblast): progesterone (by the end of the 4th month in sufficient amount); estrogens (with maximum level by fullfull-term); human chorionic gonadotropin (during the first two months); somatomammotropin (gives the fetus priority on maternal blood glucose making the mother somewhat diabetogenic). diabetogenic). 62 31 Placental Placental Variations Variations The placenta may have accessory lobes with vascular connections between them (succenturiate placenta) or there can be no vascular connections (placenta spuria). spuria). The umbilical cord may be inserted at the margin of the placenta to give it a clubclub-like appearappearance (battledore placenta). In a more extreme type of marginal insertion the umbilical cord is attached to amnion and chorion instead of the placenta (velamentous insertion of the cord). In circumvallate p. the membranes extend over the p. to form a ring before doubling back toward the margin. 63 may result in bleeding 64 32 Placenta Placenta Previa Previa If implantaimplantation is in lower part of the uterus, the placenta will partially or totally cover the internal os of the cervix. It can block the birth canal and is a common cause of bleeding in the 3rd trimester. Hemorrhage from placenta previa can be fatal to the fetus or even the mother. 65 20-weeks On the right – two monozygotic twins (boys), On the left – dizygotic girl. 66 33 67 Development of fetal membranes in twins (A) Cleavage was before trophoblast formation – different amnion & chorion. (B) Cleavage was after trophoblast formation,but before amnion development – same chorion but different amnions. 68 (C) Cleavage was after amnion formation – same amnion & chorion. (Langman 1981) 34 Further Further Development Development of of the the Fetal Fetal Membranes Membranes STAGE 12 End of the 4th week foregut midgut hindgut allantois Vitelline duct Connecting stalk After head and tail folding the connecting stalk is attached to the ventral surface of the embryo and allantois is partially incorporated into the embryo. By the end of the 5th week the yolk stalk and the connecting stalk merge to form umbilical cord. The midgut communicates with the yolk sac by way of a broad stalk – vitelline 69 duct. In 33-week embryo the yolk sac found in the chorionic cavity. During further development the amniotic cavity enlarges rapidly at the expense of the chorionic cavity, and the amnion begins to envelop the connecting stalk and yolk sac stalk, crowding them together and giving rise to the primitive umbilical cord. 3 weeks 4 weeks 70 35 Distally the cord contains vitelline duct and umbilical vessels. Proximally it contains intestinal loops and the remnants of allantois. allantois. By the 10th week the yolk sac is still found in the chorionic cavity, it is connected to the umbilical cord by the vitelline duct. At the end of the 3rd month the amnion has expanded so much that it comes in contact with chorion obliterating the chorionic cavity. The yolk sac then usually shrinks to a pearpearshaped remnant, 5 mm in diameter, connected to the midgut by the narrow yolk stalk, and is gradually obliterated. 10 weeks 20 weeks 71 The The Yolk Yolk Sac: Sac: In humans is nonfunctional as far as yolk storage is concerned, Is essential in humans as an organ of primitive hemopoiesis (between the 3rd and 6th week) and sourse of primodial germ cells (in the 3rd week). 72 36 Umbilical Umbilical Cord Cord Develops from the connecting stalk which is formed by the extraembryonic mesoderm. It connects fetus and placenta It’ It’s diameter is of 11-2 cm It’ It’s length varies from 39 to 90 cm It contains two arteries and one vein (left) It contains mucoid connective tissue (Wharton jelly) The remnants of allantois and yolk sac 73 persist in it almost until fullfull-term. 20-weeks fetus with true knot of umbilical chord 74 37 12-weeks fetus inside amniotic cavity 75 Baby with amputated right foot in reason of amniotic tapes formation 76 38 Amniotic Amniotic cavity: cavity: Is filled with a watery fluid produced by the amniotic cells, Contains around 30 ml of amniotic fluid at 10 weeks of gestation, gestation, 350 ml at 20 weeks, 800800-1000 ml at 37 weeks, The fluid absorbs jolts, prevents adherence of the embryo to the amnion, allows fetal movements. The volume of fluid is replaced every 3 hours. From the beginning of the 5th month the fetus swallows its amniotic fluid (400 ml per day). Fetal urine is added to the amniotic fluid in the 5th month. This urine is mostly water as placenta is functioning as an exchange for metabolic wastes. 77 39