The placenta is a vital link between mother and fetus, supporting fetal growth through supply of oxygen and nutrients. However, it must also work to balance both maternal and fetal needs and adapt to the maternal environment to support successful pregnancy. Failure to adapt can impact maternal health and fetal growth, which may have long-lasting effects on the offspring. For this study, pregnant mice were exposed to either maternal inhalation hypoxia (MIH; 10% or 13% inspired oxygen), or food restriction (FR) between days 14-19 of gestation. To explore the role of the placenta in adverse conditions, the distinct functional zones of the mouse placenta, the endocrine junctional zone (JZ) and the labyrinth zone (LZ), which is responsible for transport, have been examined separately. Where possible, analyses have been performed on placentas from both male and female fetuses.

Fetal weight was reduced and placental weight unchanged in both sexes under MIH and FR. Gene expression analysis of the LZ in MIH identified that altered lipid handling, peroxisome proliferator-activated receptor (PPAR) signalling, and calcium binding may contribute to reduced fetal weight. Histological analysis showed a striking increase in calcium deposition, corresponding with areas of fibrosis. In the JZ, increased glycogen deposition was observed, and dysregulation of steroidogenic genes. With FR, transcriptomic changes in the LZ included genes involved in the extracellular matrix and circadian rhythms. FR also increased glycogen deposition and altered JZ cellular composition. Despite reduced food intake in dams exposed to 10% MIH, differences in maternal physiology were observed between FR and MIH. FR dams had features of a fasting response, whereas this was not observed in hypoxic dams. Proteomic analysis identified altered abundance of proteins involved in lipid metabolism in MIH and iron handling in FR. Placentally secreted proteins were detected in maternal plasma, identifying potential biomarkers to inform on placental function, and hence fetal and maternal health.

In summary, although both MIH and FR had the same overall outcome to limit fetal growth, environment-specific placental changes have been identified, underlining the integrative function of the placenta for maternal and fetal health. Future research based on this study will help to understand and characterise pathogenesis of pregnancy complications and how the placenta orchestrates both fetal and maternal health during pregnancy.