Placental Transcriptomic Changes Due to Maternal Exercise are Dependent on Maternal Diet and Offspring Sex

Abstract

While exercise (EX) is beneficial during pregnancy for both mother and child, little is known about the mechanisms by which maternal (MAT) EX mediates changes in utero. Here we examined transcriptomic signatures in the placenta following MAT EX. Female C57BL/6 mice were fed either a control or HFD (45% fat) starting at 6 wk of age, with (EX) or without access to voluntary running wheels. Mice had 24‐h access to wheels for 10 wk prior to conception until the end of the study (18.5 days post coitum). Placenta were collected from individual pups for microarray analysis in a sex‐identified fashion. In control‐fed mice, EX affected expression (± 1.4‐fold, p < 0.05) of 661 transcripts in female placenta (vs. 283 transcripts in males), while in female placenta from HFD‐fed mice,1.7‐fold more genes had altered expression due to MAT EX. Gene‐set enrichment analysis of male placenta from control‐fed dams showed that MAT EX led to enrichment of genes involved in neurotransmitter levels and glutamate signaling and decreases in lipid biosynthesis and transport, while EX in female placenta from the same dams led to increases in genes involved in muscle and brain development and decreases in hormone metabolic processes. On HFD, female placenta had a prominent decrease in oxidative phosphorylation related genes, and both sexes showed decreased glutathione metabolism genes. Specific genes were confirmed using qPCR. Our results suggest that effects of MAT EX on the placenta and presumably on the offspring are influenced by maternal habitus and are sexually dimorphic. (NIH‐NIDDK R01‐084225 and USDA‐ARS CRIS 6251‐51000‐007‐04S).