Morphological and molecular changes in the murine placenta exposed to normobaric hypoxia throughout pregnancy

Key points Exposure of pregnant mice to chronic hypoxia at 13% O2 induces fetal growth restriction but increases placental weight. Sex dimorphism induces differential responses in placental weight to hypoxia. The male placenta is heavier than the female and is associated with less severe fetal growth restriction. Increases in maternal arterial/venous blood spaces and higher protein kinase B (Akt)‐mechanistic target of rapamycin growth signalling could contribute to the heavier hypoxic placenta. Placental endoplasmic reticulum stress is elevated equally in both sexes in response to hypoxia. In comparison, oxidative stress is only apparent in female placentas. Chronic hypoxia induces down‐regulation of placental mitochondrial electron transport chain complexes protein subunits but does not cause intracellular energy depletion. Chronic hypoxia is a common complication of pregnancy, arising through malperfusion of the placenta or pregnancy at high altitude. The present study investigated the effects of hypoxia on the growth of the placenta, which is the organ that interfaces between the mother and her fetus. Mice were housed in an hypoxic environment for the whole of gestation. An atmosphere of 13% oxygen induced fetal growth restriction (1182 ± 9 mg, n = 90 vs. 1044 ± 11 mg, n = 62, P