Maternal Obesity May Alter Fetal Liver Metabolism Through Placental Signals: Study

A mother's obesity during pregnancy may influence her child's metabolic health long after birth, according to a new mouse study published in Nature Communications. Researchers found that molecular signals carried across the placenta could permanently alter how the fetal liver develops and functions.

The study focused on small extracellular vesicles (sEVs), tiny particles in the mother’s blood that can carry regulatory molecules. In obese pregnant mice, these vesicles crossed the placenta and accumulated in the fetal liver. They contained higher levels of a molecule called miR-29a-3p, which affected genes responsible for regulating DNA methylation.

This altered the fetal liver’s epigenetic programming, including changes around Pgc-1α, a key regulator of glucose production in the liver. The gene became active earlier than normal during fetal development.

The effects persisted into adulthood. Male offspring exposed to the altered maternal signals developed glucose intolerance and reduced insulin sensitivity, even when they were given a normal diet after weaning.

Researchers strengthened the findings by transferring small extracellular vesicles from obese pregnant mice into healthy recipients. Their offspring developed similar metabolic problems. Vesicles obtained from obese pregnant women also produced comparable effects in mice, suggesting that the mechanism may be biologically relevant across species.

Importantly, researchers found that removing or neutralizing miR-29a-3p largely reversed the metabolic changes, pointing to the molecule as a potential target for future research.

The findings expand the Developmental Origins of Health and Disease (DOHaD) concept, suggesting that maternal metabolic stress may influence fetal development not only through nutrients and hormones but also through regulatory RNA molecules that modify epigenetic programming.

However, the research was conducted primarily in mice, so it does not yet prove that the same mechanism occurs in humans. Researchers are now investigating whether miR-29a-3p levels in human cord blood are associated with metabolic health during childhood.

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