Ожирение матери во время беременности навсегда меняет обмен веществ у сыновей

A mother's obesity during pregnancy may send molecular signals across the placenta that permanently alter her son's liver metabolism, according to a new study in mice published in Nature Communications. The research traces this effect to a maternal sEV–miRNA–epigenetic axis that links fetal liver programming to long-term metabolic health. In diet-induced obese mice, maternal plasma sEVs crossed the placenta and accumulated in fetal liver. These vesicles carried elevated miR-29a-3p, which suppressed multiple DNA methylation regulators and remodeled the fetal liver methylome. One affected locus, Pgc-1α-a master switch for hepatic gluconeogenesis-became hypomethylated and prematurely active in fetal life. Male offspring later developed glucose intolerance and reduced insulin sensitivity in adulthood, even on a normal diet after weaning. Transplanting sEVs from obese pregnant mice into healthy recipients reproduced the offspring metabolic phenotype. The same effect occurred when mice received sEVs from plasma of obese pregnant women, suggesting cross-species conservation. Engineered sEVs loaded with miR-29a-3p alone sufficed to induce the defects, while neutralizing this microRNA in maternal sEVs largely reversed them. The findings add a new layer to the Developmental Origins of Health and Disease (DOHaD) framework: maternal metabolic stress can be transmitted not only through nutrients and hormones, but also via regulatory RNAs that cross the placenta and rewrite fetal epigenetic programs. This mechanism may help explain why some individuals born to obese mothers face lifelong metabolic risks, even with a healthy postnatal diet. More broadly, the work offers a fresh angle on certain birth defects and developmental anomalies whose causes remain elusive. Fetal organogenesis relies on precise epigenetic timing; maternal sEV–RNA signals that arrive at the wrong dose or developmental window could derail that schedule. While this study focused on liver metabolism, the same principle may extend to other organs and disease contexts. We are now following up in human cohorts to see whether cord blood miR-29a-3p levels correlate with childhood metabolic traits. If so, this could become an early biomarker for offspring metabolic risk." Prof. Li Liang of Nanjing University, corresponding author Source: Journal reference: Song, H., et al. (2026). Maternal obesity programs offspring metabolic dysfunction via small extracellular vesicle-mediated epigenetic remodeling. Nature Communications. DOI: 10.1038/s41467-026-77161-4. https://www.nature.com/articles/s41467-026-77161-4