Placental transport in response to altered maternal nutrition

Abstract

The mechanisms linking maternal nutrition to fetal growth and programming of adult disease remain to be fully established. We review data on changes in placental transport in response to altered maternal nutrition, including compromized utero-placental blood flow. In human intrauterine growth restriction and in most animal models involving maternal undernutrition or restricted placental blood flow, the activity of placental transporters, in particular for amino acids, is decreased in late pregnancy. The effect of maternal overnutrition on placental transport remains largely unexplored. However, some, but not all, studies in women with diabetes giving birth to large babies indicate an upregulation of placental transporters for amino acids, glucose and fatty acids. These data support the concept that the placenta responds to maternal nutritional cues by altering placental function to match fetal growth to the ability of the maternal supply line to allocate resources to the fetus. On the other hand, some findings in humans and mice suggest that placental transporters are regulated in response to fetal demand signals. These observations are consistent with the idea that fetal signals regulate placental function to compensate for changes in nutrient availability. We propose that the placenta integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensors. Together, these signals regulate placental growth and nutrient transport to balance fetal demand with the ability of the mother to support pregnancy. Thus, the placenta plays a critical role in modulating maternal-fetal resource allocation, thereby affecting fetal growth and the long-term health of the offspring.

Figure 1. The placental barrier in the human term placenta

The figure represents a cross-section of the human placenta. The insert to the right shows a schematic illustration of the placental barrier, which at term mainly consists of the synctytiotrophoblast cell (ST) and the fetal capillary (FC) endothelial cell. Of these structures it is primarily the two polarized syncytiotrophoblast plasma membranes, the microvillous (MVM) and the basal plasma membrane (BPM) that restrict the transfer of molecules like ions and amino acids. ST, syncytiotrophoblast; N, nucleus of syncytiotrophoblast cell; IVS, intervillous space; SA, spiral artery; VT, villous tree; UC, umbilical cord. Reproduced by permission from Elsevier Ltd.

Figure 2. Placental nutrient transport in response to maternal under-nutrition: two models

Schematic representation of the two models proposed for the regulation of placental function in response to maternal under-nutrition (see text for details). The fetal demand model (bottom) predicts that the fetus signals to the placenta to up-regulate placental growth and nutrient transport to meet fetal nutritional demands. In the placental nutrient sensing model(top) the placenta responds to maternal nutritional cues, resulting in down-regulation of placental nutrient transporters, which leads to decreased fetal nutrient availability and IUGR.

Figure 3. Placental nutrient sensing and fetal demand: an integrated model

We propose that the placenta integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensors, such as mammalian target of rapamycin (mTOR) signaling. These signals then regulate placental growth and nutrient transport to balance fetal demand with the ability of the mother to support pregnancy. Thus, the placenta plays a critical role in modulating maternal-fetal resource allocation, thereby affecting fetal growth and the long-term health of the offspring. See text for detailed explanation. IGF-II, insulin-like growth factor II; PTHrp, parathyroid hormone related peptide.