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.

Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation

“…This occurred despite reduced placental expression of the amino acid transporter gene Slc38a1 in litters of α/+ dams (also at D19 along with decreased Slc38a2). Similar disparity between Slc38a gene expression and transport of MeAIB in vivo has been observed in placentas in which growth regulatory genes (15) or the maternal environment have been affected in rodents (3)(4)(5)(6)(7). These findings suggest that there are temporal differences between the expression, translation, and membrane trafficking of amino acid transporters in the placenta and that measuring placental expression of Slc38a genes provides little information with respect to actual transport function in vivo.…”

“…As the interface between the mother and fetus, the placenta is central to this tug-of-war over nutrient allocation. Genetic and dietary manipulations during pregnancy as well as reciprocal crosses between breeds of different sizes indicate that the placenta can adapt dynamically to both fetal signals of nutrient demand and maternal signals of nutrient availability to ensure appropriate allocation of available resources (3)(4)(5)(6)(7)(8)(9). The fetus and mother, therefore, have to cooperate to optimize both offspring and maternal fitness, but to date, little is known about the relative importance of fetal versus maternal genomes in balancing resource allocation at the placental level.…”

Developmental origins of NAFLD: a womb with a clue

“…In humans, increased maternal insulin resistance, independent of excessive gestational weight gain, mediates fetal adiposity 45 , and increased maternal insulin resistance in mice results in progressive development of postnatal lipid deposition in the offspring 46 . Although insulin produced by the mother does not cross the placenta, excessive insulin resistance during pregnancy might directly increase placental inflammation, altering nutrient transfer to the fetus 47,48 . In support of an early driving role for maternal insulin resistance, fetal hepatic steatosis was reduced when NHP mothers on a highfat diet were supplemented with resveratrol, which improved maternal insulin sensitivity and placental function 49 .…”

Maternal Stress Affects Fetal Growth but Not Developmental Instability in Rabbits

“…If parallels can be drawn towards developmental buffering in mammals, then the womb may be a very stable and controlled environment such that a uterine development may be more resilient to perturbations. Placental hormone function could play a critical role here, as it regulates the maternal-fetal energy balance [45]. In food-restricted pregnant females, the placental hormone function reduces the placental capacity to transport nutrients herewith retarding fetal growth [45] as observed here.…”

“…Placental hormone function could play a critical role here, as it regulates the maternal-fetal energy balance [45]. In food-restricted pregnant females, the placental hormone function reduces the placental capacity to transport nutrients herewith retarding fetal growth [45] as observed here. In contrast to this possibility, a study of the macaque did find that daily mild stress, induced by capturing pregnant females, resulted in significantly higher dermatoglyphic asymmetry in the offspring [46].…”