by Michael Rindler, Ph.D.
Table of Contents
II. Preimplantation Stage (Blastulation)
IV. Formation of the Chorionic Villi
V. Placental Barrier Function
VI. Nutrient Transport
VII. Endocrine Functions
VIII. Transplacental Antibody Passage
IX. Transport of Infectious Agents
X. Pathology -- Hydatidiform Mole
XI. Multiple Pregnancies
Figure 1 Placental Steroid Synthesis
1 . To study the differentiation of the early embryo into a blastocyst and the formation of the inner cell mass (embryoblast) and trophoblast cell layers.
2. To learn about the process of implantation and the development of the placenta from fetal trophoblast.
3. To understand the role of the placenta in gestation as a nutritive, endocrine, and protective organ for the embryo.
4. To appreciate the consequences of abnormal placental development.
The placenta has five basic functions:
1. It serves as the barrier separating the maternal and fetal circulations.
2. It transports nutrients from mother to fetus and waste products in the other direction.
3. It is the major endocrine organ, producing both steroid and polypeptide hormones.
4. It transfers maternal antibodies to the fetus, providing immunological protection both in utero and in postnatal life.
5. It initiates parturition (birth).
The initial formation of the placenta and the trophoblast-mediated invasion of the endometrial decidua (outer layer of the endometrium) begin approximately 6 days after fertilization as the newly formed embryo undergoes implantation. Essential to this process is the formation of the trophoblast layer of cells. In order to understand the origin of the placenta, a description of the differentiation of the early embryo is provided in the next two sections.
Fetal development takes place in the uterus. Implantation of the embryo into the uterine wall occurs on the fifth or sixth day after fertilization in humans. The earliest stages of development take place in the oviduct, where the fertilized ovum, now known as a zygote, undergoes the first cleavages or cell divisions (Fig. 2.11/3.11). These divisions are generally equal so that each of the daughter cells is roughly half the size of the original predivision parent. The early divisions are fairly synchronous and little overall growth in the size of the embryo occurs during this stage. The 4-32 cell stage embryo is known as morula (from the Greek meaning mulberry) and each of the cells is called a blastomere (Fig. 2.8/3.8). The blastomeres appear identical to one another, and experimental evidence obtained from experiments with mammalian blastomeres indicates that they are still totipotent; that is, they have the ability to form any differentiated structure of the embryo. This property of blastomeres has been exploited in gene transfer experiments. Cultured cells retaining the properties of blastomeres have had their genes altered (knocked out or mutated) and then have been reintroduced into early embryos (to make transgenic animals).
The formation of the blastocyst, beginning at the 32-64 cell stage in humans, marks the first true differentiation event (Fig. 2.10/3.10). The early blastocyst forms from the morula when the cells on the outer surface near to the still intact zona pellucida form a continuous epithelial cell layer known as the trophoblast. The trophoblast layer seals off the interior of the embryo and then pumps in salt, which in turn results in the accumulation of fluid in a chamber called the blastocyst cavity or blastocoele. This is the first of four major cavities to be formed during embryogenesis ≠ the others are the intra and extraembryonic coeloms and the amniotic cavity. On one edge of the blastocyst cavity a group of cells remains aggregated together, the embryoblast (inner cell mass), whose appearance is approximately the same as that of the undifferentiated cells of the morula. These cells will give rise to all of the structures of the embryo proper, while the trophoblast will participate in the implantation process and contribute primarily to the formation of the placenta. The trophoblast cells are not only distinguished by their position in the embryo and their epithelial appearance, but have undergone irreversible genetic changes as well (such as X-inactivation, the inactivation of one of the two X chromosomes in female embryos). Their developmental fate is also fixed -- trophoblast cells cannot differentiate back into embryoblasts, while embryoblasts still retain the capability to produce trophoblasts.
The emergence of the blastocyst starts a phase of rapid growth of the embryo. As the blastocyst matures, the zona pellucida begins to disintegrate. The blastocyst, now known as a late blastocyst emerges or hatches around day 5 through a hole in the zona at its embryonic pole, that is, adjacent to the embryoblast cells. The degradation of the zona is through the action of hydrolytic enzymes produced by the newly emerging syncytiotrophoblast (see below). The late blastocyst, containing roughly 100 or so cells, is very adhesive after hatching and is ready for implantation, which occurs 5-6 days after fertilization.
Fetal development in humans occurs completely within the endometrial layer of the uterine wall (the lining of the external surface of the uterus). The blastocyst must penetrate completely into the endometrium to allow further development to occur. After attachment to the epithelial cell layer of the endometrium at the embryonic pole (Fig. 2.10/3.10), the trophoblast cells in this area undergo a differentiation process that results in their transformation into large, multinucleated, amoeba-like cells known as the syncytiotrophoblast (Fig. 3.1/4.1). The syncytiotrophoblast is a highly adhesive and invasive cell that is responsible for implantation. It is able to adhere to the epithelial lining of the endometrium using several types of receptors, including the integrins, and penetrate deep into the endometrial stroma. Proteolytic enzymes that can degrade extracellular matrix (the collagen-rich substance surrounding cells) are critically involved. The remainder of the embryo is pulled in behind. The process of implantation is essentially complete by the end of the second week of development. A blood clot known as a closing plug (fibrin coagulum) then seals the site of the initial penetration (Fig. 3.3/4.3).
Syncytiotrophoblast cells do not divide but are instead continuously generated from the remaining trophoblast layer, known now as the cytotrophoblast. Both types of trophoblast will contribute to the formation of the embryonic portion of the placenta. In the earliest stages, the syncytiotrophoblast (SCT) layer will develop spaces within it known as lacunae that participate in nutrient exchange (Fig. 3.3/4.3).
Later the SCT will penetrate and surround maternal capillaries, then the veins and finally the arteries. This leads to the establishment of blood filled cavities within the SCT known as maternal sinusoids (Fig. 3.4/4.4). The direct contact between maternal blood and the trophoblast layer provides the embryo with a rich source of nutrients, which enter the growing embryo by diffusion prior to the formation of the fetal circulatory system. The nearby maternal decidual cells also provide important nutrient substances to the embryo. Ordinarily, the invasion of blood vessels is perceived by the body as an injury and would induce a wound-healing response accompanied by clotting of the blood. However, a natural anti-clotting agent, tissue factor, is produced by the maternal decidual cells and is thought to prevent clotting from occurring.
Maternal blood vessels of the uterine wall and fetal vessels in the placenta are relatively deficient in smooth muscle. By contrast, most large blood vessels in the adult have extensive layers of smooth muscle cells surrounding them. Smooth muscle cells are influenced by hormones released into the circulation which induce them to contract or relax, thereby regulating the size of the lumen of the vessels. Placental circulation is designed to be resistant to the actions of vasoconstrictive hormones. So, for example, when epinephrine is released into the maternal circulation due to circumstances such as sudden fright, there is little reduction in blood flow to the fetus since the placental vessels have much less smooth muscle and do not contract much. Nonetheless, the fetus is at risk when there are disturbances in maternal circulation, such as occurs in pre-eclampsia, a common condition characterized by elevated maternal blood pressure.
The process of early differentiation and implantation is an intricate one, and a sizable fraction of fertilized ova are thought never to implant. Studies conducted over the last 50 years on spontaneously and electively aborted fetuses have given researchers an indication of the rates of defective embryos and fetal wastage in the general population. These studies have led to the conclusion that most spontaneous abortions occur in the first trimester. It is difficult to know precisely what is occurring during the critical first two weeks after fertilization, but it is estimated that perhaps as many as 60% of all embryos have serious defects and that a large proportion of these are weeded out very early in embryogenesis. Thus, it is likely that most of the defective embryos are eliminated before the mother is aware of anything unusual. In addition, many may never implant for unknown reasons.
Implantation occurs in the uterine wall about 99% of the time, most often in the posterior wall. Ectopic pregnancy, where implantation occurs at abnormal sites can be a life threatening condition to the mother and fetus (Fig. 3.8/4.8). Implantation at the cervical opening of the uterus leads to a condition where the placenta seals off the opening, known as placenta previa. In this rare circumstance, the fetus can go to term but usually causes much bleeding. Delivery is often by Caesarean section. More commonly, implantation occurs in the oviduct (tubal pregnancy), probably due to impeded or improper transport of the embryo. If it is in the extrauterine portion, it will generally rupture the tube by the 8th week, resulting in the death of the embryo and severe hemorrhaging and danger of infection for the mother (Fig. 3.9/4.9). If implantation occurs in the intrauterine portion of the tube, appropriate placental circulation can be established and the fetus can develop somewhat further, although probably not to term. Implantation at other sites, such as the ovary or cervix, is very rare and usually results in spontaneous abortion. Implantation in the abdominal cavity may also occur very rarely. In this case, the fetus can occasionally go to term, although this type of implantation might compromise the health of the mother by damaging internal organs (Fig. 3.10/4.10).
After penetration of the maternal blood vessels by the trophoblast, the chorionic villi form. Primary villi have only syncytiotrophoblast (SCT) on the outside with cytotrophoblast (CT) in the center (Fig. 4.15/5.11). At a later stage, extraembryonic mesoderm migrates into the core of the primary villi to form the secondary villi. Differentiation of the extraembryonic mesoderm leads to the formation of tertiary villi, which have the fetal blood vessels inside of them. In humans, the fetal and maternal circulations are always separated by the synctiotrophoblast and this constitutes the fetal-maternal barrier that is so important (Fig. 4.16/5.12). Cytotrophoblasts will migrate to the maternal side across a class of tertiary villi called anchoring villi, which extend from the fetal to the maternal side. These cells will form a seal, the outer cytotrophoblastic shell, between the maternal and fetal tissue at the decidual plate. Villi continue to branch forming an extensive network, increasing surface area available for nutrient exchange (Fig. 6.8/7.8). In summary, mature villi have, from maternal to fetal side, a layer of SCT, CT directly underneath the SCT, extensive spongy connective tissue, and capillaries.
During gestation, the placenta will continue to grow and mature. In the first trimester, there are greater barriers to placental transfer since there is an intact cytotrophoblast layer underlying the syncytiotrophoblast, more extensive intravillous stroma and smaller villous vessels (Fig. 6.8/7.8). However, by term, exchange is more efficient. The CT layer is absent except for small residual foci of CTs, the stroma is greatly reduced and the placental vasculature is far more extensive.
Maternal tissue also contributes to the placenta. The functional layer of the uterine wall that is shed at parturition is called the decidua and is identified according to where it is found (Fig. 6.10/7.10). The tissue directly apposed to the placenta is called decidua basalis. The superficial layer covering the remainder of the fetus is known as decidua capsularis and the rest of the uterine wall is called decidua parietalis. The capsularis and parietalis will fuse together as the fetus grows to entirely fill the uterine cavity.
The mature placenta is a pancake-shaped structure roughly 25 cm. in diameter (Fig. 6.14/7.14). Also known as the afterbirth, it detaches from the wall of the uterus during parturition and is expelled shortly after the fetus. On the fetal side of the placenta itself, a network of chorionic blood vessels converge onto the umbilical veins and artery. This surface is smooth in appearance due to the covering of embryonic membranes (amnion). The lobulated maternal side resembles 'brown cauliflower' because it is divided into structure/function units known as cotyledons (~50). Each cotyledon is separated from the next by connective tissue (Fig. 6.13/7.13). From the fetal side, branches of the umbilical artery and veins enter the highly anastomosing tree of branched villi and form capillary beds within them. On the maternal side, blood from spiral arteries in the endometrium enters the cotyledon and bathes the villi, eventually exiting through maternal veins. The circulation in the placenta is sluggish to allow exchange of nutrients and waste products.
Primate placentas have what is known as a hemichorial placenta where the maternal and fetal circulations remain completely separated. The barrier function of the placenta is maintained primarily by the SCT (Fig. 6.8/7.8). These gigantic cells have hundreds of nuclei within them and are formed by the fusion of mononuclear CT precursors into a syncitium. Between SCT are tight junctional complexes that allow slow passage of ions and small molecules but restrict movement of larger molecules. Obviously, maternal and fetal blood cells do not cross the barrier (except when pieces of fetal tissue break off ≠ see below). Thus, to be efficiently transported across the barrier, most nutrients must cross the plasma membranes of the SCT. There is little exchange of large maternal and fetal proteins across the barrier (with the exception of immunoglobulins ≠ see below). Once a substance has penetrated the SCT layer there is no particular barrier associated with CT cells, the stromal cells, or fetal capillary vessels, which are porous in this region.
Modes of placental transfer include:
Other Fetal Membranes -- To some extent, nutrients, water and gases can also cross the amnion,allowing exchange between the maternal circulation and the amniotic fluid.
The placental trophoblast cells synthesize the steroid hormones progesterone and estrogen and are the only major source after the first trimester, when the corpus luteum degenerates. Both hormones are required for the maintenance of the maternal decidua. In their absence, the decidua will degenerate and the fetus cannot remain attached to the uterine wall.
In general, the principle source of progesterone is through de novo synthesis by trophoblast using cholesterol obtained through the uptake of maternal LDL (see Figure 1). The fetal adrenal synthesizes pregnenolone during gestation, which crosses into the placenta for conversion to progesterone, providing an alternative precursor. Estrogen is produced from dehydroepiandrosterone sulfate (DHAS) synthesized by the fetal adrenal gland. Fetal steroids, including cortisol, are produced in response to progressive increases in fetal adrenocorticotropin (ACTH) production [ACTH stimulates adrenal steroid synthesis] across gestation. This axis is also important for initiating parturition (see below).Placental Peptide Hormones
SCTs and CTs are a rich source of a large number of peptide hormones required for placental or fetal function. These include:
1) human Chorionic Gonadotropin (hCG) - a 36,700 dalton glycoprotein which binds to the LH receptor of the ovarian corpus luteum to stimulate massive maternal ovarian progesterone production until 8-10 weeks gestation, at which time placental progesterone production is adequate to maintain the pregnancy. hCG is produced by the SCTs and its synthesis is positively modulated by CT-derived GnRH (gonadotropin releasing hormone) and negatively modulated by CT-derived inhibin and activin. hCG also stimulates the Leydig cells in the fetal testes to produce testosterone, promoting sexual differentiation in male fetuses.
hCG is first detectable in the maternal circulation around day 10 after ovulation and peaks at 10 weeks. It is also present in the urine and one of the principle molecules used to detect pregnancy. Because Down syndrome pregnancies produce lower amounts of hCG, the assessment of hCG levels in the maternal circulation at 16 weeks gestation is recommended as the primary biochemical screening test for fetal Down syndrome.
2) human Placental Lactogen (hPL) - a 25,000 dalton glycopeptide with 94% homology to growth hormone and 67% homology to prolactin. It is produced by the SCT. hPL acts as a potent anti-insulin and lipolytic agent in the maternal circulation to increase the availability of glucose, amino acids, free fatty acids and ketones for the fetus. It has the side effect of making the mother mildly 'diabetic' that is, having glucose levels above normal after meals (insulin normally lowers blood glucose).
3) Corticotropin releasing hormone (CRH) -- a 31 amino acid glycopeptide originally identified in the hypothalamus, where its release into the portal circulation increases pituitary adrenocorticotropin (ACTH) release which, in turn, enhances adrenal cortisol production (see above). CRH has been found to be synthesized in the placenta, fetal membranes (amnion and chorion) and the uterine decidua in amounts that increase dramatically near term.
While hypothalamic release of CRH is inhibited by glucocorticoids establishing a negative feed-back loop, placental, fetal membrane and decidual synthesis is stimulated by glucocorticoids, creating a potential positive feed-back loop. Newly synthesized placental CRH will stimulate the fetal pituitary and the placenta itself to produce corticotropin (hcACTH, see below), which results in stimulation of adrenal production of the steroid cortisol (a corticosteroid).
CRH can enhance prostaglandin production by the fetal membranes and decidua to potentially initiate parturition (labor and delivery). Prostaglandins as well as oxytocin stimulate uterine muscle contraction. Rapid increase in circulating CRH, potentially driven by rising fetal and maternal cortisol production, occurs during the final few weeks of pregnancy. This suggests that CRH is part of the biological clock mechanism regulating the onset of parturition. It is not known how cortisol itself inhibits progesterone function, thereby disrupting decidual function. The best hypothesis is that it does so by binding to the same receptors and antagonizing the progesterone response. In other animals, like sheep, cortisol lowers progesterone levels by activating an enzyme that converts androgen precursors to estrogens instead. In human placenta, however, this enzyme is not present.
4) human chorionic corticotropin (hcACTH). As mentioned above, this hormone stimulates cortisol production. Its synthesis by the placenta is regulated by CRH.
5) GnRH -- hypothalamic releasing hormone also produced by trophoblast stimulates release of hCG and production of steroid hormones.
The placenta is an immunologically privileged organ. This means that the mother does not ordinarily make antibodies against the trophoblast itself even though it may express foreign, paternally derived antigens on its surface. Part of the explanation for this is that the placenta produces substances which locally suppress the immune response (the nature of these is unknown). In addition, effective immune responses against cells require the presence of so-called histocompatibility antigens produced by all cells. Trophoblast cells are an exception, producing instead their own unique histocompatibility antigen. This antigen not only cannot participate in the immune response, it is thought to suppress the maternal immune response.
Antibodies are not synthesized by the fetus prenatally. Maternal IgG (which is the major type of antibodies produced) is specifically transported across the placenta, particularly late in gestation. As mentioned above, specific receptors for IgG exist on the microvillar surface of the trophoblast which transport it across the SCT cells. Since the fetus is a separate immunological entity, if the mother is exposed to immunologically unique, paternal-derived fetal antigens, she will generate anti-fetal antigen antibodies. In the case of erythrocyte (red blood cell) antigens such as Rh, maternal antibodies can cross the placenta to cause alloimmune hemolytic anemia (killing of erythrocytes), also known as Rh disease, in the fetus. Rh disease can cause cardiac failure due to fluid accumulation (hydrops fetalis), intrauterine death, or even severe jaundice leading to mental retardation. In most cases, Rh disease does not affect the first pregnancy. Exposure to fetal cells does occur naturally late in gestation when pieces of placental villi break off and enter the maternal circulation, often lodging in the lungs. The fetal red blood cells therein can trigger a maternal immune response, but significant antibody accumulation would take place only very late in gestation and therefore the fetus is not affected significantly. However, in subsequent pregnancies the problem potentially may become much more severe as the maternal immune response is more vigorous. Rh immunoglobulins (a sort of blocking antibody) given to the mother can prevent damage to the fetus.
A very similar type of antibody response can affect platelets. A mother who does not express the PLA-1 platelet antigen, but whose fetus does, can produce anti-PLA-1 antibodies that can cross the placenta to cause profound alloimmune thrombocytopenia (deficiency of platelets) with fetal intracerebral hemorrhage. Again, this is more common after the first pregnancy.
Maternal auto-antibodies that cause autoimmune diseases in the mother can also cross the placenta: a) anti-acetylcholine receptor antibodies, leading to neonatal Myasthenia Gravis (impaired muscular function); b) anti-TSH receptor antibodies, leading to fetal and neonatal Graves disease (impaired thyroid function); c) anti-ribonucleoprotein antibodies, leading to congenital heart block; and d) anti-phospholipid antibodies causing fetal or neonatal thrombosis (blood clots).
A number of viruses, including cytomegalovirus, rubella (German measles), varicella-zoster (chicken pox), measles, and poliovirus, can cross the placenta and infect fetal tissues. Rubella in particular was a significant pathological agent before the advent of vaccines. It was a major cause of craniofacial abnormalities including congenital deafness. Today, the most important virus that can infect the fetus is HIV, which is transmitted to about 1/4 of infants of HIV-infected mothers who are not being treated with anti-viral drugs. AZT and other HIV virus-suppressing drug therapies administered to mothers with HIV have reduced this percentage dramatically in the last few years. Fetal infection is believed to occur around the time of parturition, either through microscopically damaged areas of the placenta that allow maternal blood to enter the fetus or during delivery. Cesarean delivery before the onset of labor is therefore recommended in these cases. Because maternal antibodies are present for the first 2-3 months after birth, conventional AIDS testing, which detects circulating antibodies to HIV in the bloodstream, cannot be used to detect HIV infection in newborns.
Bacteria and other protozoa do not ordinarily cross the barrier. Exceptions include treponema palladium (syphilis) and toxoplasma gondii that can cause abnormalities of the brain and eyes. Toxoplasma is primarily transmitted by maternal ingestion of uncooked meat.
Rarely (perhaps 1:500-1:1000 pregnancies), the process of growth and invasion of the maternal endometrium by trophoblast goes awry. This results in the death of the fetus and the production of tumors (hydatidiform mole) consisting exclusively of trophoblastic tissue. Moles produce abnormally high levels of circulating hCG, which is used to diagnose them. There are two kinds of such moles. One is a generally benign lesion that is not very invasive called partial hydatidiform mole. The more invasive complete variety, a choriocarcinoma, maintains the highly invasive properties of the early SCT and, if untreated, will generally metastasize (migrate to and colonize other sites). It has characteristic swollen villi. Modern chemotherapeutic techniques have improved survival rates for women, even those with invasive or metastatic moles, and most are now curable.
Recently, it has been found that hydatidiform moles have chromosomal abnormalities. Complete moles are diploid, but both sets of chromosomes are paternal, that is, derived solely from sperm. Most of them have XX sex chromosomes and are believed to arise from monospermic fertilization (the X chromosome is essential, therefore no YY moles can develop). In this case, the oocyte pronucleus is lost and the sperm pronucleus apparently undergoes an initial duplication of its chromosomes without cleavage to produce a diploid nucleus. Occasionally, complete moles are XY, indicating that they arose from dispermic fertilization, but the maternal chromosomes are nonetheless not present. Partial moles are triploid, with two paternal sets of chromosomes and one maternal set. Most of these arise from dispermic fertilization or possibly by a single abnormal diploid sperm.
The inheritance of paternal chromosomes as a cause of hydratidiform mole raises the puzzling question of why it should matter to the developing oocyte what the origin of the chromosomes is. Developmental biologists have long been able to experimentally produce a similar phenomenon in mouse oocytes by replacing the male or female pronucleus in fertilized ova with another of the opposite origin. This results in diploid embryos with two sets of paternal or maternal chromosomes. Interestingly, those ova having a maternal set form recognizable embryos with greatly reduced placental development. By contrast, those with paternal chromosomes form trophoblast and a mass of placental tissue resembling moles but generally lack embryonic tissue. The results imply that maternal chromosomes regulate embryoblast development while paternal chromosomes are responsible for trophoblast development.
The manifestation of phenotypically different characteristics depending on whether inheritance is maternal or paternal is known as genetic imprinting. Imprinting is thought to have evolved to control placenta formation but its effects are not limited to early development. The severity and age of onset of a number of genetic diseases differ depending on the parent from whom the mutated gene is inherited. These include Huntington's chorea (Woody Guthrie's disease), neurofibromatosis, and Wilm's tumor (a kidney tumor). In one case when the defective gene is inherited from the father, it causes Prader-Willi syndrome and from the mother a distinct condition called Angelman syndrome. While both syndromes are characterized by mental retardation and by characteristic facial traits, other features differ between the two. With respect to the mechanisms governing imprinting, in some cases it has been shown that two copies of the affected chromosome were inherited from a single parent (uniparental disomy) probably after a trisomic conceptus lost one of the chromosomes in an early division. On the molecular level, differential methylation of genes coupled with cis acting transcriptional enhancers have been shown to be involved, but the detailed mechanisms are not well understood.
Twinning may occur when there are several oocytes that undergo ovulation (dizygotic = fraternal), as occurs relatively frequently when the mother takes fertility drugs. Less commonly, monozygotic (identical) twins are derived from a single embryo when the embryo separates into two during early embryogenesis. Monozygotic twins formed by an early separation (morula blastomere stage), like dizygotic twins, always have separate placentas and amniotic sacs (Figs. 6.17/ 7.18, 6.18/7.19). If implantation is close together, the placentas may fuse together but the vascular systems remain separate. When monozygotic twins are generated later in embryogenesis, at the blastocyst stage, the inner cell mass separates into two and the twins will have a common chorionic cavity and placenta but almost always have separate amniotic cavities (Fig. 6.18/7.19). In this case, the circulations in the placenta may be separate or may have anastomoses between them. If the splitting of the inner cell mass occurs very late in embryogenesis, which is rare, the twin embryos will share the same amniotic cavity as well as a common placenta. In very rare cases, the embryos may fail to separate completely and are called conjoined twins (Fig. 6.21/7.22). Complications from multiple pregnancies include death of one or more of the fetuses because of compression, lack of adequate nutrients, or unbalanced blood supply, particularly when there are vascular anastomoses. Furthermore, low birth weight and prematurity are very common, putting the newborns at great risk. Infant mortality is high (as much as 20%) for twin pregnancies.
What is the function of the inner cell mass and the trophoblast layer in the early embryo?
At what stage does implantation take place?
What role does the syncitiotrophoblast play in villus formation? The cytotrophoblast?
What important structures derive from the extra-embryonic mesoderm in the chorion and villi?
What happens to the chorionic cavity? Why does the membrane around the fetus actually consist of two layers?
What are decidual cells? Spiral arteries?
What is the difference between primary, secondary, and tertiary villi?
What specific changes occur in the trophoblast and stroma of the placental villi during gestation and what consequences do these changes have on nutrient exchange?
A woman who has already had a successful pregnancy has a subsequent series of miscarriages. She is Rh-, PLA-1-, but her husband is Rh+, PLA-1+. What could be the cause of the problem?
Approximately 1/4 of HIV-positive, untreated (i.e., no anti-HIV drug regimen) mothers transmit their virus to the fetus, yet all of their children initially test HIV positive. Why is this?
What pathogenic agents can cross the placenta? Most pathogens do not cross. Why not?
What are the major hormones synthesized by the syncytiotrophoblast and cytotrophoblast? What is the function of hCG, hPL, and CRH? What is the importance of progesterone? Why is it produced by the placenta when the corpus luteum is a rich source?
How do nutrients cross the placenta? Gases? Steroid hormones?
What is the basis for dizygotic twins? Monozygotic? For monozygotic twins what determines how many placentas, chorions, and amnions there will be?
What is a conjoined twin and what is the cause of it?
What is a hydatidiform mole? What chromosomal anomalies have been found in association with the two types, partial and complete?
A woman of child-bearing age suddenly develops severe lower abdominal pain and calls her physician. She believes she may have missed her last two periods. What specific diagnosis would be important to consider and what tests could be conducted to confirm a potential diagnosis?