After fertilization, the next major hurdle for reproduction in eutherian mammals is trophoblast differentiation, which is required for implantation. This in turn is followed lock step by the rapid assembly of these cells into a functional placenta. Although there is a great deal of species-to-species variation in the assemblage process per se, the functional results are always the same. For the remainder of gestation, whether an additional 16 days in a mouse or 9 months in a human, the development of the embryo/fetus and the health of the mother critically depend on the placenta. In humans, this fact is graphically illustrated by the spectrum of pregnancy complications that are associated with just one type of pathology, superficial attachment of the placenta to the uterus. In some cases fetal growth stalls, leading to intrauterine growth retardation. In other instances the effects extend to the mother, who may suddenly show signs of widespread vascular damage so severe that death may quickly ensue, hence the name eclampsia (Gk. eklampsis, sudden flash or development). Although the placenta is a transient organ, it has evolved to meet the significant challenge of accommodating the nutritional and growth-regulatory needs of the developing fetus within the overall physiological environment of the mother. Not only must maternal physiology change to meet these needs of the fetus, but changes must also occur to prepare the mother for the distinct needs of the newborn after parturition. For successful reproduction, the physiology of pregnancy in the mother must therefore be significantly different from the physiology of the nonpregnant adult female, with differences in numerous systems, including blood vessel growth, hematopoiesis, immune response, metabolism, steroid hormone production, behavior, and mammary development. The widespread physiological changes that occur during pregnancy must be temporally coordinated among many organs and tissues, an organizational task that typically falls to circulating hormones, and a strong case can be made for the placenta as the most important source of these hormones that reprogram maternal physiology during pregnancy.

The placenta is a rather unique endocrine organ. First, since the hormone-producing placental trophoblast cells are derived from the fertilized egg, the placenta is genetically distinct from the maternal targets of the placental hormones (except, of course, in matings of highly inbred parents, such as inbred strains of mice). Second, the organ is transient, growing and developing during pregnancy but disappearing at parturition. Third, placental hormones are often present in the circulation at concentrations far in excess of what is found for similar hormones in the nonpregnant adult. And fourth, the placenta produces a number of hormones that are not otherwise synthesized in the organism, suggesting that a distinct set of hormones are required to bring about the physiological changes of pregnancy rather than simply producing more of certain hormones. In these properties, the placenta can be seen to resemble a “pharmacological” organ, dispensing high levels of foreign compounds over a restricted time period. The placental hormones almost certainly target receptors and signaling pathways in the mother that exist in the nonpregnant state, again much like pharmaceuticals, and therefore the novel and highly expressed placental hormones may provide valuable probes to identify receptors and signaling pathways that have otherwise remained obscure. In rodents, ruminants, and primates (including humans), prominent among these placental-specific hor-