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Updated: Sep 25, 2026

Stable Isotope In-Vivo Labeling for Mass-Spectrometry Identification of Paternal Metabolites Transferred from Sperm to Oocyte During Fertilization
Published on: June 17, 2025
Maternal obesity programs offspring metabolic dysfunction via small extracellular vesicle-mediated epigenetic
Huichen Song1,2,3, Dameng Li4, Lina Ma5
1Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Abstract:
Maternal obesity is linked to heightened metabolic disease risk in offspring, but the mediators of this intergenerational effect remain unclear. Using a diet-induced obesity (DIO) mouse model, we showed that maternal circulating small extracellular vesicles (sEVs) crossed the placenta and delivered obesity-associated miRNAs to the fetal liver, with lasting consequences for insulin sensitivity in male offspring. Among these miRNAs, miR-29a-3p was pathologically elevated and targeted both DNA methyltransferases and demethylases, thereby reshaping the DNA methylation landscape. This included hypomethylation of the Pgc-1α locus, a key regulator of gluconeogenesis, which resulted in premature activation of hepatic gluconeogenesis that contributed to the persistent metabolic dysfunction in adulthood in male offspring. These findings identify a transplacental sEV-miRNA-epigenetic axis that perturbs fetal metabolic programming and may represent a conserved mechanism underlying the developmental origins of metabolic disease.
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