Optimal fetal growth and development is dependent on placental function. Intrauterine growth restriction and obesity alter placental angiogenesis and oxidative stress (ROS). We investigated the effects a high-fat diet (HFD) and endurance exercise in pregnant rats born small on placental Vascular Endothelial Growth Factor A (VEGFA), Placental Growth Factor (PGF) and NADPH-Oxidase 4 (NOX4) expression.
Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham (Control) surgery on E18 in Wistar-Kyoto rats. Female F1 offspring were fed a chow or HFD (23% fat) from 5 weeks of age. Rats were sedentary or exercised on a treadmill from 4 weeks before mating and throughout pregnancy or during pregnancy only. F2 placental labyrinth tissues were collected and weighed at post-mortem (E20). VEGFA, PGF and NOX4 expression were analysed by qPCR.
HFD increased Control and Restricted maternal body and dorsal fat weights. HFD Sedentary mothers had reduced female placental Nox4 expression irrespective of maternal birth weight. In HFD Sedentary Control mothers VEGFA expression was reduced in both male and female placenta. Exercise before and during pregnancy in Chow-fed mothers increased female fetal and male placental weights, with no changes in mRNA expression. However, Exercise during pregnancy only in Chow-fed mothers reduced female placental weight and increased male and female VEGFA and PGF expression. Whereas Exercise during pregnancy only in mothers fed a HFD increased NOX4 expression regardless of maternal birth weight.
Exposure to a maternal HFD lead to sex-specific dysregulation of placental angiogenesis and ROS gene expression. However, exercise affected these factors differently depending on whether it was initiated before or only during pregnancy. This data highlights that more research is required to investigate the timing of exercise interventions and the mechanisms by which it improves placental and fetal outcomes.