Organization of the Placenta The term hemochorial and the older term hemochorioendothelial are used to describe human

placentation. The terms are derived as follows: hemo refers to maternal blood, which directly bathes the syncytiotrophoblast; chorio is for chorionplacenta, which in turn is separated from fetal blood by the endothelial wall of the fetal capillaries that traverse the villous core (hence the older term hemochorioendothelial). The characteristics of this type of placentation are illustrated in Figures 3 11 and 312. Chorionic Villi Chorionic villi can first be distinguished in the human placenta on about the 12th day after fertilization. Mesenchymal cords, derived from extraembryonic mesoderm, invade the solid trophoblast columns, forming the secondary villi. After angiogenesis occurs from the mesenchymal cores, the resulting villi are termed tertiary. Maternal venous sinuses are tapped early in the implantation process, but until the 14th or 15th day after fertilization, maternal arterial blood does not enter the intervillous space. By about the 17th day, fetal blood vessels are functional, and a placental circulation is established. The fetalplacental circulation is completed when the blood vessels of the embryo are connected with the chorionic blood vessels. Some villi, in which failure of angiogenesis results in a lack of circulation, become distended with fluid and form vesicles. A striking exaggeration of this process is characteristic of the development of hydatidiform mole (see Chap. 11, Hydatidiform Mole [Molar Pregnancy]). The trophoblasts of the villus consist of the outer layer of syncytium and an inner layer of cytotrophoblasts, also known as Langhans cells. Proliferation of the cytotrophoblasts at the tips of the villi produces the trophoblastic cell columns or anchoring villi. These structures are not invaded by fetal mesenchyme but are anchored to the decidua at the basal plate. Thus, the base of the intervillous space, the maternal-facing side, consists of cytotrophoblasts from the cell columns (trabeculae), the covering syncytium of the trophoblast shell, and decidua of the basal plate. The base of the chorionic plate forms the roof of the intervillous space and consists of two layers of trophoblasts externally and fibrous mesoderm internally. The "definitive" chorionic plate is formed by 8 to 10 weeks as the amnionic and primary chorionic plate mesenchyme fuse together. This formation is accomplished by expansion of the amnionic sac, which also surrounds the connective stalk and the allantois and joins these structures to form the umbilical cord (Kaufmann and Scheffen, 1992). Villus Ultrastructure The electron microscopic studies of Wislocki and Dempsey (1955) permitted a functional interpretation of the fine structure of the placenta. There are prominent microvilli on the syncytial surface, corresponding to the so-called brush border described by light microscopy (Fig. 313). Associated pinocytotic vacuoles and vesicles are related to the absorptive and secretory placental functions. The microvilli act to increase the surface area that will have direct contact with maternal blood. It is the contact between the trophoblastic surface and maternal blood that is the defining characteristic of the hemochorial type of placenta. Depending on the number of trophoblastic epithelial layers, the human hemochorial placenta can be subdivided into hemodichorial or hemomonochorial (Enders, 1965). The inner layer of the villithe cytotrophoblasts and the associated basal laminais more prominent during the first trimester of gestation (Fig. 314). Later in gestation, however, the layer of cytotrophoblasts inside the syncytium is no longer continuous, with only scattered cells present at term, creating a narrower hemomonochorial barrier that facilitates transport of nutrients and oxygen to the fetus.

Placental Growth and Maturation Placental Growth In the first trimester, growth of the placenta is more rapid than that of the fetus, but by approximately 17 weeks postmenstruation (from the last menstrual period), placental and fetal weights are approximately equal. At term, the placental weight may be roughly one sixth that of fetal weight. According to Boyd and Hamilton (1970), the average placenta at term is 185 mm in diameter and 23 mm in thickness, with a volume of 497 mL and a weight of 508 g. These measurements vary widely, and there are multiple variant forms of the human placenta and several types of umbilical cord insertions, which are discussed in Chapter 27. Viewed from the maternal surface, the number of slightly elevated convex areas, called lobes, varies from 10 to 38. These lobes are incompletely separated by grooves of variable depth, overlying the placental septa, which arise from folding of the basal plate. These grossly visible lobes have also been referred to as "cotyledons", however, this use should be avoided, because they bear no relation to the functional units supplied by each primary villus, which are termed either lobules or cotyledons. The total number of lobes remains the same throughout gestation, and individual lobes continue to grow, although less actively in the final weeks (Crawford, 1959). Placental weights vary considerably, depending on how the placenta is prepared. If the fetal membranes and most of the cord are left attached and the adherent maternal blood clot is not removed, the weight may be greater by nearly 50 percent (Thomson and colleagues, 1969). Placental Maturation As the villi continue to branch and the terminal ramifications become more numerous and smaller, the volume and prominence of cytotrophoblasts decrease. As the syncytium thins, the fetal vessels become more prominent and lie closer to the surface. The stroma of the villi also exhibits changes as gestation progresses. In placentas of early pregnancy, the branching connective tissue cells are separated by an abundant loose intercellular matrix. Later, the stroma becomes denser and the cells more spindly and more closely packed. Another change in the stroma involves the infiltration of Hofbauer cells, which represent fetal macrophages. These cells are nearly round with vesicular, often eccentric nuclei and very granular or vacuolated cytoplasm. Hofbauer cells are characterized histochemically by intracytoplasmic lipid and by phenotypic markers specific for macrophages. They increase in numbers and maturation state as pregnancy progresses. Although phagocytic, they have an immunosuppressive phenotype (Vince and Johnson, 1996). In addition, they can produce a variety of cytokines and are capable of paracrine regulation of trophoblast functions (Cervar and colleagues, 1999). Some of the histological changes that accompany placental growth and maturation provide an increased efficiency of transport and exchange to meet increasing fetal metabolic requirements. Among these changes are a decrease in thickness of the syncytium, a significant reduction of cytotrophoblast cells, a decrease in the stroma, an increase in the number of capillaries, and an approximation of these vessels to the syncytial surface. By 4 months, the apparent continuity of the cytotrophoblasts is broken, and at term, the covering of the villi may be focally reduced to a thin

layer of syncytium with minimal connective tissue where the fetal capillaries appear to abut the trophoblast. The villi become dominated by thin-walled capillaries. Other changes in placental architecture, however, can cause a decrease in the efficiency of placental exchange if they include a substantial portion of the exchange area. These changes include thickening of the basal lamina of the trophoblast or capillaries, obliteration of certain fetal vessels, and fibrin deposition on the surface of the villi in the basal and chorionic plates as well as elsewhere in the intervillous space.