Maternal exercise programs placental miR-495-5p-mediated Snx7 expression and kynurenic acid metabolic pathway induced by prenatal high-fat diet: based on miRNA-seq, transcriptomics, and metabolomics.

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Poor intrauterine environments increase the prevalence for chronic metabolic diseases in offspring, whereas maternal exercise is an effective measure to break this vicious intergenerational cycle. Placenta is increasingly being studied to explore its role in maternal-fetal metabolic cross-talk. The association between placental miRNA and offspring development trajectories has been established, yet the specific role and mechanism thereof in maternal exercise-induced metabolic protection remain elusive. Here, C57BL/6 female mice were subjected to either a normal control or a high-fat diet (HFD), half of the HFD-fed dams were housed with voluntary wheel running for 3 weeks before and during gestation. At embryonic day 18.5, we sacrificed parturient mice and then conducted miRNA-seq, transcriptomic, and metabolomic profiling of the placenta. Our data revealed that maternal HFD resulted in significant alterations in both miRNA and gene expressions, as well as metabolic pathways of the placenta, whereas prenatal exercise negated these perturbations. The common differentially expressed transcripts among three groups were enriched in multiple critical pathways involving energy expenditure, signal transduction, and fetal development. Through integrated analysis of multi-omics data, we speculated that maternal exercise reversed the suppression of miR-495-5p induced by HFD, thereby inhibiting miR-495-5p-targeted Snx7 and modulating kynurenic acid production. These datasets provided novel mechanistic insight into how maternal exercise positively affects the metabolic homeostasis of offspring. The discovered important miRNAs, mRNAs, and metabolites could be promising predictive and therapeutic targets for protecting offspring metabolic health.