Chorionic villi, which constitute the functional tissue of the placenta, consist of a connective tissue core and a two-layered epithelial cellular covering. The outermost layer consists of syncytiotrophoblasts. Immediately under this is a layer of cells, referred to as cytotrophoblasts, from which the syncytiotrophoblast derives. Thus, cytotrophoblasts are numerous in the early placenta but relatively sparse in the placenta of late pregnancy.

The syncytiotrophoblast not only covers the surface of the chorionic villi but also extends from the anchoring villi onto the surface of the basal plate and onto the placental septa. As a consequence, the entire compartment in which maternal blood is contained is walled by syncytiotrophoblasts.

Except for relatively rare rupturing of capillary walls, which is more common at delivery, fetal and maternal blood do not mix. This separation of the fetal and maternal blood, referred to as the placental barrier, is maintained primarily by the layers of fetal tissue. Starting at the fourth month, these layers become very thin to facilitate the exchange of products across the placental barrier. The thinning of the wall of the villus is due to the loss of the inner cytotrophoblastic layer. At its thinnest, the placental barrier consists of the syncytiotrophoblast, a sparse discontinuous inner cytotrophoblast layer, basal lamina of the trophoblast, connective tissue of the villus, basal lamina of the endothelium, and endothelium of the fetal placental capillary in the tertiary villus. Thus, this barrier bears a strong resemblance to the air-blood barrier of the lung, with which it has an important parallel function, namely, the exchange of oxygen and carbon dioxide, in this case between the maternal blood and the fetal blood. In addition, metabolic substrates and products, hormones and other regulatory molecules, and antibodies that confer passive immunity on the fetus also routinely cross the placental barrier. Unfortunately, so too do potentially dangerous agents such as alcohol, nicotine, drugs, viruses, exogenous hormones, and heavy metals that can harm the embryo or fetus.

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