Placental Responses to Changes in the Maternal Environment Determine Fetal Growth

Abstract

Placental responses to maternal perturbations are complex and remain poorly understood. Altered maternal environment during pregnancy such as hypoxia, stress, obesity, diabetes, toxins, altered nutrition, inflammation, and reduced utero-placental blood flow may influence fetal development, which can predispose to diseases later in life. The placenta being a metabolically active tissue responds to these perturbations by regulating the fetal supply of nutrients and oxygen and secretion of hormones into the maternal and fetal circulation. We have proposed that placental nutrient sensing integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensing signaling pathways to balance fetal demand with the ability of the mother to support pregnancy by regulating maternal physiology, placental growth, and placental nutrient transport. Emerging evidence suggests that the nutrient-sensing signaling pathway mechanistic target of rapamycin (mTOR) plays a central role in this process. Thus, placental nutrient sensing plays a critical role in modulating maternal-fetal resource allocation, thereby affecting fetal growth and the life-long health of the fetus.

Keywords: fetal programming; maternal–fetal exchange; mechanistic target of rapamycin; placental nutrient sensing; pregnancy; syncytiotrophoblast.

Figure 1

Placental nutrient sensing model. The placenta integrates maternal signals with information from nutrient sensing signaling pathways such as mechanistic target of rapamycin (mTOR) to regulate placental function. As a result, fetal growth is matched to the ability of the maternal supply line to allocate resources to the fetus. Thus, the placental responses to maternal signals influence fetal growth and the long-term health of the offspring.

Figure 2

Placental mTOR as a nutrient sensing signaling pathway. mTOR integrates maternal signals such as nutrients and growth factors to modulate the transport of nutrients from the maternal to the fetal circulation. mTORC1 modulates the trafficking of AA transporters possibly through differential ubiquitination mediated by NEDD4-2. Inhibition of NEDD4-2 will result in increased localization of AA transporters in the plasma membrane (Rosario et al., , ; Chen et al., 2015).