Maternal obesity remodels nutrient transporttranscriptional programs in early mouse embryonic and extraembryonic cell lineages

Oxidative phosphorylation genes were broadly suppressed, and genes involved in hypoxia, cytoskeleton remodeling, and cell migration were enriched among upregulated pathways. Chromatin accessibility changed in a few lineages, most notably in extraembryonic visceral endoderm and parietal trophoblast giant cells. Differently accessible chromatin was enriched in binding motifs for retinoic acid receptors.

Indeed, genes involved in retinol and lipoprotein transport were suppressed, and RNA in situ hybridization confirmed reduced expression of retinol transporters Ttr, Rbp4, and Stra6, and lipoprotein transporter Apoa1 in visceral yolk sac. Thus, obesity during pregnancy causes early transcriptional dysregulation that impairs retinoic acid and lipoprotein transport at the maternal-fetal interface, suggesting a mechanism through which maternal obesity could influence long-term developmental outcomes.