The Placenta: The Lost Neuroendocrine Organ

The placenta long has been underappreciated and understudied by the scientific community. Improper function of this critical organ causes fetal abnormalities, preterm labor, and the most common disease of pregnancy, preeclampsia. Despite the importance of the placenta, understanding of its role in fetal development, especially at a molecular level, is crude. Sadly, understanding of placental function may be compared with the knowledge of kidney function 50 years ago in that researchers can describe the anatomy but not the biology. As an endocrine organ, the placenta produces a wide array of hormones that affect both mother and fetus as well as the development of the placenta itself. Most research on placental endocrinology has focused either on parameters of fetal growth or placentally induced changes in maternal physiology that support pregnancy. The possibility that placental hormones may have direct effects on the developing fetus deserves increased attention. Placental endocrine function can be disrupted by abnormal gene expression, infection, or prematurity, resulting in long-term damage from loss of the normal hormonal milieu. In this review, we focus on placental endocrine function related to fetal well-being, particularly neurodevelopment. Better understanding of this function may open new avenues to therapeutic treatments to improve developmental outcome in fetuses and infants at high risk of developmental brain damage. Placental Function: Historical View The intimate connection between the fetus and placenta has been recognized throughout history, but understanding of placental function has undergone many shifts. In early ancient Egypt, for example, the placenta was invested with extraordinary power as the alter ego or twin of the infant. (1) Thus, the recognition of the king as a living god led to the remarkable development of the Cult of the Royal Placenta. The Pharaoh’s placenta was retained and protected throughout his life; it was the symbol that led the royal standard on the earliest known royal Egyptian inscriptions. At death, it was ritually cut open and likely buried with him to proceed into the afterlife. Despite such reverence, there is no indication that a function for the placenta was recognized beyond general “protection” of the fetus. Later, Hellenistic philosophers recognized the nutritive function of the placenta, believing that the fetal and maternal circulations were in direct contact and that the fetus was partially nourished by it, either through the umbilical cord or by suckling on the placenta. (1) This understanding persisted into the Renaissance. Leonardo da Vinci depicted this intimate *Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, Calif. Abbreviations CNS: central nervous system