Diet-induced obesity affects miRNA expression in plasma extracellular vesicles of pregnant women

However, the underlying mechanisms by which maternal factors drive these long-lasting effects remain to be fully elucidated. In our study, we have demonstrated that in diet-induced-obesity (DIO) pregnant mice, maternal small extracellular vesicles (sEV) in circulating system have the ability to cross the placental barrier and reach the liver of fetal mice, exerting a sustained adverse impact on offspring insulin sensitivity.

Further investigations have revealed that pathogenically increased miR-29a-3p in maternal sEV from DIO mice can be delivered into livers of fetal offspring. Elevated miR-29a-3p subsequently alter epigenetic state in fetal liver via targeting several key methyltransferases and demethylases, interrupting the DNA methylation landscape, including hypomethylation of PGC-1α. Such epigenetic remodeling abnormally promotes early hepatic gluconeogenesis at fetal stage that contribute to the adult metabolic disturbance in offspring.