New research reveals that maternal obesity can send molecular messages via placental extracellular vesicles, altering fetal liver metabolism early in development and potentially increasing lifelong health risks for offspring.
A new mouse study has found that maternal obesity can send molecular messages through the placenta that alter a male offspring’s liver metabolism long before birth, with effects that persist into adulthood. Published in Nature Communications, the research points to a pathway involving extracellular vesicles, or sEVs, tiny particles that carry microRNAs and other biological signals between cells. The authors say this adds to earlier work showing that obesity can disturb placental function itself, including changes in placental structure, lipid handling and gene activity.
In the study, obese pregnant mice had circulating sEVs that passed into the fetal liver and carried higher levels of miR-29a-3p, a microRNA linked to gene regulation. Those vesicles appeared to reduce several DNA methylation regulators and alter the fetal liver’s epigenetic pattern, including changes at Pgc-1α, a gene involved in glucose production. Offspring later showed poorer glucose control and reduced insulin sensitivity, even after being weaned onto a normal diet. Earlier studies have also suggested that maternal obesity can reshape placental lipid metabolism, which may help explain how the intrauterine environment becomes disrupted.
The effect was not limited to one strain of mice. When researchers transplanted sEVs from obese pregnant mice into healthy recipients, they reproduced the same metabolic problems in offspring. The team reported a similar outcome when it used sEVs taken from the plasma of obese pregnant women, suggesting the mechanism may be conserved across species. In a further test, engineered sEVs loaded only with miR-29a-3p were enough to trigger the same defects, while blocking the microRNA in maternal vesicles largely reversed them. Related research has already linked maternal obesity to fatty liver disease in offspring through changes in liver macrophages, known as Kupffer cells, and to altered hepatic microRNA pathways affecting lipid metabolism.
Prof. Li Liang of Nanjing University, the study’s corresponding author, said the group is now examining human cohorts to see whether cord blood miR-29a-3p tracks with later metabolic risk. “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.” If confirmed, the findings could widen the developmental origins of health and disease framework by showing that maternal metabolic stress may be carried not only by nutrients and hormones, but also by RNA messages that rewrite fetal gene programmes at critical stages of development.
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