week, the anatomical arrangements necessary for physi- ologic exchanges between the mother and embryo have been established. By the end of the fourth week, a complex vascular network develops in the placenta, allowing maternal-embryonic exchanges of gases, nutrients, and metabolic waste products.
Chorionic villi cover the entire chorionic sac until the beginning of the eighth week (see Fig. 8-1D and Fig. 8-2).
As this sac grows, the villi associated with the decidua capsularis are compressed, reducing the blood supply to them. These villi soon degenerate, producing a relatively avascular bare area, the smooth chorion (see Fig. 8-1D).
As these villi disappear, those associated with the decidua basalis rapidly increase in number, branch profusely, and enlarge (Fig. 8-3). This bushy part of the chorionic sac is the villous chorion, or chorion frondosum (see Fig. 8-1E and Fig. 8-4).
Homeobox genes (HLX and DLX3) expressed on the trophoblast and blood vessels help to regulate the devel- opment of the placenta.
The size of the chorionic sac is useful in determining the gestational age of embryos in patients with uncertain men- strual histories. Growth of the chorionic sac is extremely rapid between the 5th and 10th weeks of development.
Modern ultrasound devices permit detection of the chorionic sac when it has a median diameter of 2 to 3 mm (see Fig.
8-4). Chorionic sacs with this diameter indicate a gestational age of approximately 18 days after fertilization.
ULTRASONOGRAPHY OF
CHORIONIC SAC
C H A P T E R 8 PLACENTA AND FETAL MEMBRANES 73
Figure 8–1 Development of placenta and fetal membranes. A, Coronal section of the uterus showing elevation of the decidua capsularis and the expanding chorionic sac at 4 weeks.
B, Enlarged illustration of the implantation site. The chorionic villi were exposed by cutting an opening in the decidua capsularis. C to F, Sagittal sections of the gravid (pregnant) uterus from the 5th to 22nd weeks, showing the changing relationship of the fetal membranes to the decidua. In F, the amnion and chorion are fused with each other and with the decidua parietalis, thereby obliterating the uterine cavity.
A B
C D
E F
Uterine tube
Decidua capsularis
Uterine cavity
Amnion Uterine cavity
Amnion
Intervillous space
Villous chorion Umbilical vesicle
Villous chorion
Decidua basalis
Smooth chorion
Chorionic sac (smooth chorion)
Site of internal os of uterus Mucous plug Mucous plug
Mucous plug
Vagina
Decidua basalis Amniotic sac
Decidua basalis
Placenta Decidua capsularis Decidua parietalis
Decidua parietalis Amniochorionic
membrane Degenerating decidua capsularis
Chorionic cavity Umbilical vesicle
Umbilical vesicle
Chorionic villi on chorionic sac Decidua parietalis
Myometrium
Mucous plug Mucous plug
74 BEFORE WE ARE BORN ESSENTIALS OF EMBRYOLOGY AND BIRTH DEFECTS
Figure 8–2 Lateral view of a spontaneously aborted embryo at Carnegie stage 14, approxi- mately 32 days. The chorionic and amniotic sacs have been opened to show the embryo.
Amnion covering chorionic vessels
Chorionic villi of villous chorion
Chorionic vessels
Smooth chorion
Umbilical cord
Maternal blood enters the intervillous space from the spiral arteries in the decidua basalis (see Fig. 8-5); these arteries pass through gaps in the cytotrophoblastic shell and discharge blood into the intervillous space. This large space is drained by endometrial veins that also penetrate the cytotrophoblastic shell. The numerous branch villi, arising from stem villi, are continuously showered with maternal blood as it circulates through the intervillous space. The blood in this space carries oxygen and nutri- tional materials that are necessary for fetal growth and development. The maternal blood also contains fetal waste products, such as carbon dioxide, salts, and prod- ucts of protein metabolism.
Amniochorionic Membrane
The amniotic sac enlarges faster than the chorionic sac.
As a result, the amnion and smooth chorion soon fuse to form the amniochorionic membrane (see Fig. 8-1F). This composite membrane fuses with the decidua capsularis and, after disappearance of this part of the decidua, adheres to the decidua parietalis. It is the amniochorionic
membrane that ruptures during labor. Preterm rupture of this membrane is the most common event leading to premature labor. When the amniochorionic membrane ruptures, the amniotic fluid escapes through the cervix and vagina.
Placental Circulation
The many branch chorionic villi of the placenta provide a large surface area where materials (e.g., oxygen, and nutrients) are exchanged across the very thin placental membrane interposed between the fetal and maternal circulations (Fig. 8-6B and C). It is through the branch villi that the main exchange of material between the mother and the fetus takes place. The placental mem- brane consists of extrafetal tissues.
Fetoplacental Circulation
Poorly oxygenated blood leaves the fetus and passes through the umbilical arteries (see Fig. 8-5 and Fig. 8-7).
At the attachment of the umbilical cord to the placenta, these arteries divide into a number of radially disposed
C H A P T E R 8 PLACENTA AND FETAL MEMBRANES 75
blood (see Fig. 8-7). This system provides a very large surface area for the exchange of metabolic and gaseous products between the maternal and fetal blood. Nor- mally, no intermingling of fetal and maternal blood occurs. The well-oxygenated fetal blood in the fetal capil- laries passes into thin-walled veins that follow the chori- onic arteries to the site of attachment of the umbilical cord, where they converge to form the umbilical vein.
This large vessel carries oxygen-rich blood to the fetus (see Fig. 8-5).
Maternal-Placental Circulation
The maternal blood enters the intervillous space through 80 to 100 spiral endometrial arteries in the decidua basalis (see Fig. 8-5). The entering blood is at consider- ably higher pressure than that in the intervillous space, so the blood spurts toward the chorionic plate. As the pressure dissipates, the blood flows slowly around the branch villi, allowing an exchange of metabolic and gaseous products with the fetal blood. The blood eventu- ally returns through the endometrial veins to the maternal circulation (see Fig. 8-7). Reductions of uteroplacental circulation result in fetal hypoxia (decreased level of oxygen) and intrauterine growth restriction. The intervil- lous space of the mature placenta contains approximately 150 ml of blood that is replenished three or four times each minute.
Figure 8–3 A human chorionic sac containing a 13-week fetus that aborted spontaneously.
The villous chorion is where chorionic villi persist and form the fetal part of the placenta. In situ, the cotyledons were attached to the decidua basalis and the intervillous space was filled with maternal blood.
Smooth
chorion Elbow of
13-week-old fetus
Cotyledon
Intervillous space Villous
chorion
Figure 8–4 Endovaginal axial scan of a gravid uterus showing a 3-week chorionic sac (arrow) in the posterior endometrium (decidua). There is a bright (echogenic) ring of chorionic villi (open arrows) around the sac. M, Myometrium.
M
chorionic arteries that branch freely in the chorionic plate before entering the chorionic villi (see Fig. 8-5). The blood vessels form an extensive arteriocapillary venous system within the chorionic villi (see Fig. 8-6A), which brings the fetal blood extremely close to the maternal
C H A P T E R 8 PLACENTA AND FETAL MEMBRANES 75.e1
Courtesy E. A. Lyons, MD, Professor of Radiology, Obstetrics and Gynecology, and Anatomy, University of Manitoba, Health Sci- ences Centre, Winnipeg, Manitoba, Canada.)
76 BEFORE WE ARE BORN ESSENTIALS OF EMBRYOLOGY AND BIRTH DEFECTS
Placental Membrane
The membrane consists of the extrafetal tissues that sepa- rate the maternal and fetal blood. Until about 20 weeks, the placental membrane consists of four layers (see Fig.
8-6B and C): syncytiotrophoblast, cytotrophoblast, con- nective tissue of the villus, and endothelium of the fetal capillaries. After the 20th week, microscopic changes occur in the branch villi that result in the cytotrophoblast becoming attenuated in many villi.
Eventually, cytotrophoblastic cells disappear over large areas of the villi, leaving only thin patches of syncytio- trophoblast. As a result, the placental membrane at full term consists of only three layers in most places (see Fig. 8-6C). In some areas, the placental membrane
Figure 8–5 Illustration of a transverse section through a full-term placenta, showing (1) the relation of the villous chorion (fetal part of placenta) to the decidua basalis (maternal part of placenta); (2) the fetal placental circulation; and (3) the maternal-placental circulation. Maternal blood flows into the intervillous spaces in funnel-shaped spurts from the spiral arteries, and exchanges occur with the fetal blood as the maternal blood flows around the branch villi. The inflowing arterial blood pushes venous blood out of the intervillous space and into the endo- metrial veins. Note that the umbilical arteries carry poorly oxygenated fetal blood (shown in blue) to the placenta and that the umbilical vein carries oxygenated blood (shown in red) to the fetus. Only one stem villus is shown in each cotyledon, but the stumps of those that have been removed are indicated. Arrows indicate direction of maternal (red and blue) and fetal (black) blood flow.
Amniochorionic membrane
Chorionic plate
Fetal circulation Umbilical vein
(O2-rich blood) Umbilical arteries (O2-poor blood)
Intervillous space
Main stem villus
Stump of main stem villus
Amnion Smooth chorion Decidua parietalis
Branch villi
Placental septum
Decidua basalis
Myometrium
Endometrial
veins Endometrial arteries Maternal circulation
Cytotrophoblastic shell Spiral
artery
Anchoring villus
becomes markedly thinned. At these sites, the syncytio- trophoblast comes in direct contact with the endothelium of the fetal capillaries to form a vasculosyncytial placen- tal membrane.
Only a few substances, endogenous or exogenous, are unable to pass through the placental membrane. In this regard, the membrane acts as a true barrier only when the molecule or organism has a certain size, configura- tion, and charge. Most drugs and other substances in the maternal plasma pass through the placental membrane and are found in the fetal plasma (see Fig. 8-7).
During the third trimester, numerous nuclei in the syn- cytiotrophoblast of the villi aggregate to form syncytial knots—nuclear aggregations (see Fig. 8-6C). These knots
C H A P T E R 8 PLACENTA AND FETAL MEMBRANES 77
Placental Transport
The large surface area of the placental membrane facilitates the transport of substances in both directions between the placenta and the maternal blood. Almost all materials are transported across the placental membrane by one of the following four main transport mechanisms:
simple diffusion, facilitated diffusion, active transport, and pinocytosis.
Passive transport by simple diffusion is usually char- acteristic of substances moving from areas of higher to lower concentration until equilibrium is established.
Facilitated diffusion requires a transporter but no energy.
Active transport against a concentration gradient requires energy. This mechanism of transport may involve carrier molecules that temporarily combine with the substances to be transported. Pinocytosis is a form of endocytosis in which the material being engulfed is a small amount of extracellular fluid. Some proteins are transferred very slowly through the placenta by pinocytosis.
Transfer of Gases. Oxygen, carbon dioxide, and carbon monoxide cross the placental membrane by simple diffusion. Interruption of oxygen transport for several minutes endangers the survival of the embryo or fetus.
The efficiency of the placental membrane approaches that regularly break off and are carried from the intervillous
space into the maternal circulation. Some knots may lodge in capillaries of the maternal lungs, where they are rapidly destroyed by local enzyme action. Toward the end of pregnancy, fibrinoid material forms on the surfaces of villi (see Fig. 8-6C).
Functions of Placenta
The placenta has many functions:
•
Metabolism (e.g., synthesis of glycogen)•
Transport of gases and nutrients as well as drugs and infectious agents•
Protection by maternal antibodies•
Excretion of waste products•
Endocrine synthesis and secretion (e.g., human chori- onic gonadotropin)Placental Metabolism
The placenta synthesizes glycogen, cholesterol, and fatty acids, which serve as sources of nutrients and energy for the embryo or fetus. Many of the metabolic activities of the placenta are critical for two of its other major activi- ties: transport and endocrine secretion.
Figure 8–6 A, Illustration of a stem chorionic villus showing its arteriocapillary-venous system. The arteries carry poorly oxygenated fetal blood and waste products from the fetus, whereas the vein carries oxygenated blood and nutrients to the fetus. B and C, Sections through a branch villus at 10 weeks’ gestation and at full term, respectively. The placental membrane, composed of extrafetal tissues, separates the maternal blood in the intervillous space from the fetal blood in the capillaries in the villi. Note that the placental membrane becomes very thin at full term. Hofbauer cells (B) are believed to be phagocytic cells.
A
B
C
Fetal capillaries
Arteries Branch villus
Endothelium of fetal capillary
Connective tissue core of villus
Hofbauer cells
Persisting
cytotrophoblast cells
Fibrinoid material
Oxygen- rich fetal blood
Placental membrane Oxygen-poor blood in fetal capillary
Cytotrophoblast Syncytiotrophoblast
Syncytial knot Placental
membrane Arteriocapillary
venous network
Syncytio- trophoblast
Chorionic plate Amnion Vein
78 BEFORE WE ARE BORN ESSENTIALS OF EMBRYOLOGY AND BIRTH DEFECTS
significant amounts, except for a slow transfer of thyrox- ine and triiodothyronine. Unconjugated steroid hormones cross the placental membrane relatively freely. Testoster- one and certain synthetic progestins also cross the pla- centa (see Chapter 19).
Electrolytes. These compounds are freely exchanged in significant quantities, each at its own rate. When a mother receives intravenous fluids with electrolytes, they also pass to the fetus and affect the fetal water and elec- trolyte status.
Drugs and Drug Metabolites. Most drugs and drug metabolites cross the placenta by simple diffusion. Drugs taken by the mother can affect the embryo or fetus, directly or indirectly, by interfering with maternal or placental metabolism. Some drugs cause major birth defects (see Chapter 19). Fetal drug addiction may occur after maternal use of drugs such as heroin, and neonates may experience withdrawal symptoms. Most drugs used for the management of labor readily cross the placental membrane. Depending on the dose and timing in relation to delivery, these drugs may cause respiratory depression of the neonate. Neuromuscular blocking agents such as succinylcholine, which might be used during operative obstetrics, cross the placenta in only very small amounts.
All sedatives and analgesics affect the fetus to some degree.
Inhaled anesthetics can also cross the placental membrane and affect fetal breathing if used during parturition.
of the lungs for gas exchange. The quantity of oxygen reaching the fetus is generally flow-limited, rather than diffusion-limited. Fetal hypoxia results primarily from factors that diminish either uterine blood flow or fetal blood flow through the placenta. Nitrous oxide, an inha- lation analgesic and anesthetic, also readily crosses the placenta.
Nutritional Substances. Nutrients constitute the bulk of substances transferred from the mother to the embryo or fetus. Water is rapidly exchanged by simple diffusion and in increasing amounts as pregnancy advances.
Glucose produced by the mother and placenta is quickly transferred to the embryo or fetus by facilitated diffusion mediated primarily by GLUT-1—an insulin-independent glucose carrier. Maternal cholesterol, triglycerides, and phospholipids are transferred. Although free fatty acids are transported, the amount transferred appears to be relatively small with a preference toward long-chain poly- unsaturated fatty acids. Amino acids cross the placenta to the fetus in high concentrations by active transport.
Vitamins cross the placental membrane and are essential for normal development. A maternal protein, transferrin, crosses the placental membrane and carries iron to the embryo or fetus. The placental surface contains special receptors for this protein.
Hormones. Protein hormones such as insulin and pituitary hormones do not reach the embryo or fetus in
Figure 8–7 Transport across the placental membrane. The extrafetal tissues, across which transport of substances between the mother and fetus occurs, collectively constitute the pla- cental membrane. IgG, Immunoglobulin G; IgM, immunoglobulin M; IgS, immunoglobulin S.
Intervillous space
Fetal capillary Via umbilical
arteries
Placental
membrane Lungs Kidneys
Via umbilical vein
Endometrial veins Maternal
venous system
Endometrial spiral arteries Waste Products
Carbon dioxide, water, urea, uric acid, bilirubin
Other Substances Red blood cell antigens Hormones
Oxygen and Nutrients Water
Carbohydrates Amino acids Lipids Electrolytes Hormones Vitamins Iron
Trace elements
Rubella Drugs (e.g., alcohol) Poisons and carbon monoxide
Viruses Antibodies, IgG, and vitamins
Other Substances
Bacteria, heparin, IgS, and IgM Nontransferable Substances
Harmful Substances
Toxoplasma gondii
Cytomegalovirus
C H A P T E R 8 PLACENTA AND FETAL MEMBRANES 79
The concentration of hCG in the maternal blood and urine rises to a maximum by the eighth week and then declines.
The placenta also plays a major role in the production of steroid hormones (i.e., progesterone and estrogens). Pro- gesterone is essential for the maintenance of pregnancy.
Uterine Growth During Pregnancy
The uterus of a nonpregnant woman is in the pelvis. It increases in size during pregnancy to accommodate the growing fetus. As the uterus enlarges, it increases in weight and its walls become thinner. During the first trimester, the uterus expands out of the pelvic cavity, and by 20 weeks, it usually reaches the level of the umbilicus.
By 28 to 30 weeks, the uterine fundus reaches the epigas- tric region, the area between the xiphoid process of the sternum and umbilicus.