Maternal extracellular vesicles cross the placenta to deliver microRNAs directly to the fetal liver, causing lasting metabolic dysfunction in male offspring, according to research published in Nature Communications on 25 August 2026. Researchers demonstrated the transmission mechanism in a diet-induced obesity mouse model.
Circulating small extracellular vesicles from obese mothers carried elevated levels of miR-29a-3p into fetal liver tissue. This microRNA targeted both DNA methyltransferases and demethylases, reshaping the fetal DNA methylation landscape. That disruption led to hypomethylation at the Pgc-1α locus, a key genetic regulator of gluconeogenesis.
Hypomethylation triggered premature activation of hepatic gluconeogenesis in the developing mice. This premature activation led to persistent metabolic dysfunction and reduced insulin sensitivity once male offspring reached adulthood. The authors noted that this transplacental axis might represent a conserved biological mechanism governing the developmental origins of metabolic disease.
Huichen Song, Dameng Li, and Lina Ma contributed equally as lead authors on the paper. The research team included investigators from Nanjing Drum Tower Hospital, Nanjing University, Xuzhou Medical University, Qilu Medical University, and the Chinese Academy of Medical Sciences. P. Xie, C. Xu, W. Li, J. Liu, H. Shi, B. Sun, S. Zhan, and Y. Kong of Nanjing University supplied experimental materials and technical assistance.
The study was received on 10 November 2025 and accepted on 18 August 2026. Funding support came from the National Natural Science Foundation of China, the National Science and Technology Major Project, the CAMS Innovation Fund for Medical Sciences, and the China Postdoctoral Science Foundation. The authors declared no competing interests.
