Epigenetic Study Links Placental Differences to Fetal Health

New research led by the US National Institutes of Health (NIH) has found that male and female placentas exhibit distinct genetic expression patterns that may influence pregnancy outcomes and long-term health differences between sexes.

The study, published in Nature Communications, examined DNA methylation patterns in placental tissue from male and female fetuses. Researchers identified 2,497 previously unreported sites in the genome where methylation levels differed by sex. Of all observed sites, 66.9% of increased methylation occurred in male placentas, while 33.1% appeared in female placentas.

These findings suggest that epigenetic markers may contribute to sex-specific outcomes such as birth weight, risk of preterm birth, and susceptibility to certain adult diseases, argues the study. For example, increased methylation near the CCDC6 gene was observed in male placentas; previous studies have linked reduced activity of this gene to premature birth. 

Similarly, changes in methylation near the FNDC5 gene, associated with the production of the hormone irisin, were linked to lower gene expression in male placentas. Irisin plays a protective role against oxidative stress and insulin resistance. Low irisin levels have been connected to preeclampsia, a pregnancy-related hypertensive disorder. In contrast, genes showing higher activity in female placentas, such as ATP5MG and FAM83A, have been associated with later risks of asthma, hay fever, eczema, and breast cancer. The findings provide new avenues for exploring how early life biology influences lifelong health.

Male fetuses tend to grow more rapidly than females but are also more likely to experience complications such as restricted fetal growth, preeclampsia, and stillbirth. They also face a higher risk of mortality in the first year of life. Many of these disparities are believed to stem from placental dysfunction and, as the study suggests, from differential DNA methylation patterns.

The research supports ongoing efforts to better understand the biological roots of sex-based health disparities, potentially informing future interventions aimed at improving pregnancy outcomes and long-term wellness.