Fetal Membranes and Placenta

The Fetal Membranes

The fetal membranes, which are also known as the extraembryonic membranes, are membranous structures associated with the developing embryo and fetus; they protect and nourish the embryo and the fetus during their development within the uterus. They are four in number including the amnion, the yolk sac, the chorion, and the allantois. They are made of somatopleure and splanchnopleure. Somatopleure is formed by the fusion of the extraembryonic ectoderm and the extraembryonic somatic mesoderm, whereas the splanchnopleure consists of the extraembryonic endoderm and the extraembryonic splanchnic mesoderm.

Fig. 8.1. The illustration shows the four fetal membranes, the amniotic membrane, the chorionic membrane, the allantoic membrane, and the vitelline membrane and contribution of the somatopleure (dark yellow) and the splanchnopleure (dark pink) to their formation.   

The Yolk Sac

Although the name implies that this is a sac containing yolk, but in humans it does not contain yolk as do the yolk sacs in egg laying vertebrates e.g. birds.  Even though it contains no yolk in humans, the human yolk sac has several critical biological functions during early gestation, including primitive hematopoiesis and germ cell production.  It first appears as a primary yolk sac or a primary umbilical vesicle. In the 2^nd week of embryonic development, the blastocyst organizes itself into four extra-embryonic membranes that provide support for the developing embryo. The inner cell mass forms a bilaminar embryonic disc with different cells on each side. The hypoblast is the ventral one of the two laminae; it contains cells that proliferate to form the yolk sac, which is the extra-embryonic membrane that sits in the cavity of the blastocyst.

The primary yolk sac develops at the same time as the amniotic sac at about the 8^th to 11th day of embryonic development, as a vesicle known as the primary umbilical, or the primary  yolk sac. It originates from the hypoblast (the primitive endoderm) of the inner cell mass.  The primary yolk is quite transient and is rapidly replaced by the secondary or the definitive yolk sac. The function of the primary yolk sac is not clear.

Fig. 8.2. The illustration shows the primary yolk sac and the amniotic formed immediately after implantation of the blastocyst into the endometrium.

The secondary definitive yolk sac develops from the primary yolk sac on the 12th – 14th day of embryonic development. Its wall is made of splanchnopleure which is endoderm fused with splanchnopleure. In the 4th week of embryonic development part of the secondary yolk sac becomes incorporated within the gut constituting part of the midgut, whereas those  parts of the secondary yolk sac remaining outside the embryonic body form the final yolk sac.

The yolk sac gives rise to a number of cell types and tissues that include the primordial germ cells, which ultimately differentiate into the male and female gametes (sperms and ova). It also gives rise to the blood islands that differentiate into blood cells and blood vessels. It also participates to the formation of the umbilical cord. The yolk sac does not present for the full duration of pregnancy; it disappears after the first trimester.

Fig. 8.3. The illustration shows that the secondary yolk sac replaces the primary one simply by acquiring a wall made of splanchnopleure that consists of endoderm and splanchnic mesoderm.

The Allantois

The allantois, similar to the yolk sac has a wall made of splanchnopleure consisting of endoderm of the primitive gut fused with the splanchnic mesoderm. It develops as an outgrowth of the floor of the hindgut in most mammals; in humans it develops as a caudal outpocketing  of the primitive yolk sac, which becomes surrounded by mesoderm forming the body stalk. The blood vessels of the body stalk develop into the umbilical arteries that carry deoxygenated blood to the placenta. Its name is derived from its shape; it is a sausage-shaped fluid-filled hollow sac that is involved in nutrition of the embryo and excretion. In humans, the allantois appears during gastrulation before appearance of the somites.

The allantois has two major functions. One is that it is responsible for gas exchange between the developing embryo and the surrounding environment, taking oxygen in and releasing carbon dioxide out. The other function is that it is responsible for freeing the developing embryo of the waste products, which is basically nitrogenous urine waste. Thus, it represents a respiratory organ and a urinary bladder.

Although the human allantois is vestigial yet, it participates in the formation of the placenta. Its wall fuses with the chorionic wall forming the allantochorion, which is the fetal part of the placenta.  The allantoic blood vessels vascularize the chorion and amnion. The allantoic arteries emerge as branches of the dorsal aorta,  whereas the allantoic veins also known as the umbilical veins drain into the caudal or inferior vena cava via the sinus venosus. These vessels constitute the umbilical circulatory arc which supplies the placenta.

The allantoic diminishes during embryonic development and ends up as a cord of endodermal cells embedded in the umbilical cord. The proximal part of the allantois is known as the urachus which is continuous with the urinary bladder. After birth, it transforms into a fibrous cord called the median umbilical ligament.

Fig. 8.4. The illustrations show the origin and fate of the allantois. The allantois emerges as an outpocketing of the yolk sac as seen in the illustration on the left, and ends as the umbilical cord as seen in the illustration on the right.  

The Amnion

The amnion is the fluid-filled fetal membrane that immediately surrounds the developing embryo and the fetus. It protects the embryo and the fetus from external hurtful pressures and regulate the body temperature of the fetus. It facilitates free movements of the fetus thus facilitating normal development of fetus without adhesions. It also facilitates normal development of the respiratory and digestive systems. The fetus swallows the amniotic fluid and also breathes into it. The amniotic fluid has anti-inflammatory and antibacterial properties.

The amnion develops in early stages of embryonic development during implantation and gastrulation; it develops from the epiblast of the embryonic disc. In some mammals it arises by folding of the somatopleure which is an extraembryonic membrane formed by fusion of the ectoderm and the somatic mesoderm. In humans, it arises by cavitation of the inner cell mass that leads to the formation of a proamniotic cavity. This process is mediated via BMP signaling. The amniotic cavity is roofed in by a single layer of flattened, ectodermal cells constituting the amniotic ectoderm, while the floor of the cavity is made of the prismatic ectodermal cells of the embryonic disk. Outside the amniotic ectoderm there is a thin layer of somatic mesoderm that faces the mesodermal lining of the chorion. In the fourth or fifth week of the embryonic development, the amniotic fluid begins to accumulate in the amnionic cavity.

The fully developed amnionic membrane is made up of three layers that give the amniotic membrane its durability and flexibility; these three layers are:

·         The epithelium, which is the top layer of the amnion. It is a simple cuboidal epithelium.

·         The basement membrane which is a homogenous amorphous sheet that gives anchorage to the epithelium and separates it from the underlying connective tissue.

·         The stroma is the innermost and thickest of the three layers. It is a loose connective tissue that provides support to the epithelium and provide nutrients to the epithelial cells.

The amnion may be affected by a number of pathological conditions that include:

·         Chorioamnionitis: This is a bacterial infection of the amnion or chorion. Antibiotics treat it.

·         Premature rupture of membranes: This is when your amniotic sac ruptures before 37 weeks of pregnancy.

·         Amniotic band syndrome: This happens when the amnion tears or ruptures, creating loose bands of tissue inside the amniotic sac. The tissue can tangle around the fetus and restrict blood flow to its limbs. Treatment involves using prosthetics at birth, physical therapy or surgery.     

Fig. 8.5.  The illustration shows the origin and development of the amnion. As seen in the illustration on the left, it arises during implantation and gastrulation as a cavity overlying the epiblast and covered by amnioblast. At full term, as seen in the illustration on the right, it is a fluid-filled sac that totally encompasses the fetus. The amniotic membrane is fused with the chorion, together forming the amniochorion which contributes to the formation of the placenta. The fetus is connected to the placenta by the umbilical cord.   

The Chorion

The chorion develops in the second week of embryonic development spreading of mesodermal cells derived from the embryonic disc onto the inner surface of the cytotrophoblast, specifically it is derived from somatopleure which forms by the fusion of trophoblastic ectoderm and the extraembryonic mesoderm. It develops in intimate association with the developing amnion by the process of cavitation. The chorion is the outermost of the fetal membrane that completely surrounds the fetus and all other fetal membranes. It provides a strong protective covering for the embryo and participates in the formation of the placenta that provides oxygen and nourishment for the developing embryo and fetus.

During implantation, the trophoblastic cells that invade the uterine endometrium arrange themselves into two layers, an inner cytotrophoblast and an outer syncytiotrophoblast. The cytotrophoblast is made of discretely bound cells, whereas the syncytiotrophoblast is a syncytium of cells without intercellular boundaries. The syncytiotrophoblast has great capability of eroding the uterine tissue leading to burial of the blastocyst in the uterine endometrium. During this process of invasion, the syncytiotrophoblast shows projections that foreshadow the formation of the chorionic villi. Accordingly, the chorionic villi are completely covered by the syncytiotrophoblast. After formation of the placenta, the syncytiotrophoblast functions as the transporting epithelium of the placenta.  The syncytiotrophoblast stays submerged in the maternal blood constituting a placental type known as the hemochorial placenta. The fetal blood capillaries lie immediately beneath the basal lamina of the syncytiotrophoblast. The syncytiotrophoblast plays a key role in the transfer of nutrients and waste between the mother and the developing fetus, and as well as it synthesizes hormones and participates in the metabolism of proteins and lipids. In addition, the syncytiotrophoblast provides an impermeable barrier between the maternal blood and the fetal blood.

Fig. 8.6. The cytotrophoblast and the syncytiotrophoblast formed at the time of implantation of the blastocyst in the uterine endometrium surrounding the embryonic disc along with the amnion and the yolk sac. The syncytiotrophoblast shows undulations that foreshadow the formation of trophoblastic villi

The chorion is formed by the fusion of trophoblast and the extraembryonic somatic mesoderm. The fully developed chorion completely surrounds the fetus and the amnion. The chorionic membrane is made of somatopleure which is ectoderm and somatic mesoderm fused together. The ectoderm faces outwards, and the somatic mesoderm faces inwards. The somatic mesoderm of the chorion is fused with the somatic mesoderm of the amnion thus making a single membrane made of the chorion and amnion known the chorioamniotic membrane. The chorion has two parts, which are the chorion laeve and the chorion frondosum. The chorion frondosum is the part that makes up the placenta in conjunction with the decidua basalis and is characterized by the presence of chorionic villi, whereas the chorion laeve is the remaining smooth part of the chorion that surrounds the fetus.  The chorion frondosum is also referred to as the fetal part of the placenta.

Fig. 8.7. The illustration shows that the fully developed chorionic membrane completely surrounds the amniotic sac which in turn completely surrounds the fetus. The amniotic ectoderm faces the fetus whereas the chorionic ectoderm faces the endometrium. The fused somatic mesoderm of the amnion and the chorion is sandwiched between the two ectoderms.

The Placenta

The placenta is a temporary organ that forms in the uterus during pregnancy which attaches to the uterine wall and provides nutrients and oxygen to the developing embryo and fetus. It  connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother’s blood supply.  It has several other functions which include production of hormones and providing immunity to the developing fetus. The placenta begins to develop during implantation of the blastocyst into the maternal endometrium in the 7^th to the 10^th day of embryonic development with the formation of the syncytiotrophic villi. It continues to grow throughout pregnancy to satisfy the needs of the developing fetus attaining a size of up to 10 inches in length and 1 inch in thickness. It has the shape of a dark red disc rich in blood vessels. It is connected to the fetus by the umbilical cord. The umbilical blood vessels branch and rebranch within the placenta in a manner similar to that of tree trunks. In the 12^th week of pregnancy it takes over the function of the corpus luteum in the production of progesterone. In addition, it secretes a number other steroid and proteo-hormones, metabolic proteins, growth factors and cytokines that maintain pregnancy.

Fig. 8.8.  The illustration shows the component parts endometrial decidua and the embryonic chorion which contribute to the formation of the placenta.

The placenta is a fetomaternal organ that has two components, the chorion frondosum or fetal placenta, which develops from the blastocyst, and the decidua basalis or maternal placenta which develops from the maternal uterine tissue. In the early stages of the development of the chorion frondosum, the outer layer of the blastocyst becomes the trophoblast. This trophoblast surrounding the amnion proliferates and develops into two layers, a cytotrophoblast immediately surrounding the amniotic membrane and a syncytiotrophoblast overlying the cytotrophoblast. The syncytiotrophoblast is a layer comprising a multinucleated continuous cell that forms the covering surface layer of the placenta. It forms as a result of the differentiation and fusion of the underlying cytotrophoblast cells; this process continues throughout the placental development. The syncytiotrophoblast, which is also known as the syncytium secretes hCG and also contributes to the barrier function of the placenta. Most renowned of these are the human chorionic gonadotrophin (hCG), the human chorionic somatomammotropin also known as the human placental lactogen, and estrogen in addition to progesterone. hCG levels increase until about 10 weeks in pregnancy. It induces proliferation of the endometrium and helps support the growing embryo. This hormone is utilized as a marker for pregnancy; a reading of more than 25mIU/mL of β-hCG is considered positive for pregnancy.  The human placental lactogen helps prepare the mammary for breastfeeding. It also regulates metabolism to make sure that the fetus gets enough supply of nutrients.

The full-term human placenta is a flattened discoidal mass with an approximately circular or oval outline. Its normal location is the top backwall or the lateral walls of uterus. Proper development of the placenta is essential for a successful pregnancy. Abnormal locations may pose a heath thread for both the mother and the fetus.

The placenta has fetal part which the chorion and a maternal part which is the decidua basalis of uterus. The chorion comprises the cytotrophoblasts. the syncytiotrophoblast and the extraembryonic somatic mesoderm. The cytotrophoblast makes finger like projections that grow into the syncytiotrophoblast; these projections are known as the primary chorionic villi. The somatic mesoderm grows into the primary mesoderm forming the secondary chorionic villi. Blood vessels develop within the somatic mesoderm and thereafter the secondary chorionic villi become known as tertiary villi. The amniotic sac enlarges to eventually fill the chorionic sac and the amniotic membrane fuses with the chorionic membrane thus forming the amniochorionic membrane. The amniochorionic membrane fuses with the endometrial decidua thus forming the placenta. The amniochorionic membrane along with the fetal vessels constitute the chorionic plate. Parts of the decidua basalis grow into the chorionic plate dividing it into separate septa known as cotyledons, each containing stem villi. The chorionic villi provide anchorage of the chorion sac and the fetus to the endometrium. The spiral arteries of the endometrium make their way through openings in the cytotrophoblast shell and reside inside the chorionic villi where they release the maternal blood to bathe the chorionic villi in each cotyledon facilitating exchange of oxygen and nutrients between the maternal blood and the fetal blood. Even though the fetal vessels are bathed in the maternal blood, yet normally there is no mixing of maternal and fetal bloods. The umbilical cord attaches the fetus to the placenta; it comprises two umbilical arteries and one umbilical vein.

Fig. 8.9. The illustration shows the blood supply of the placenta. The placental labyrinth which is the interface for gaseous and nutrient exchange between the mother and the fetus is supplied by spiral uterine arteries. The fetal villar vessels are branches of the umbilical blood.

The human placenta is a hemochorial placenta where the embryonic chorionic membrane lies in direct contact with the maternal blood. In lower mam  nhmals other types of placentae are present such as the epitheliochorial placenta where the embryonic membrane lies in contact with the uterine epithelium, the syndesmochorial placenta where the chorion membrane lies in contact with the endometrial stromal and the endotheliochorial where the chorion membrane lies in contact with the endothelium of the uterine capillaries.

Fig. 8.10. H&E-stained section of the human placenta showing the chorionic syncytiotrophoblast in direct contact with the maternal blood. The fetal blood in the chorionic capillaries does not mix with the maternal blood; the two are separated by three types of tissues which are all fetal; they are the syncytiotrophoblast, the chorionic connective tissue stroma and the endothelium of fetal blood capillaries.

Placental anomalies

A number of conditions are related to the placenta; these include the placenta previa, the placenta accreta, the retained placenta, placental insufficiency and placental abruption.

1. Placenta previa is a result of implantation of the blastocyst in or around the cervix resulting in the placenta covering the uterine cervix completely or partially.

2. Placenta accreta results from the blastocyst eroding too deep into the uterine endometrium.

3. Placental insufficiency is a condition where the placenta does not provide enough oxygen and enough nutrients to the developing fetus.

4. Placental abruption is a condition where the placenta detaches from the uterine endometrium too early.

5. Retained placenta is when the placenta does not detach from the endometrium and comes out of the uterus after parturition.

Fig. 8.11.  The illustrations show the various grades of placenta previa increasing in severity from left to right namely low-lying placenta, marginal placenta previa, partial placenta previa, and complete placenta previa.

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