Differences in Placental Gene Expression Between Male and Female Fetuses May Impact Pregnancy Outcomes

Recent research conducted by scientists at the NIH and collaborating institutions reveals significant differences in gene activity in placentas based on fetal sex. These differences are driven by variations in DNA methylation patterns—chemical tags that regulate gene expression without altering the underlying genetic code. The study analyzed placental samples from a broad population, identifying over 2,500 DNA sites with sex-specific methylation patterns. Notably, nearly 67% of significant methylation changes were more prominent in male placentas, while the rest were observed in females.

These methylation variations influence the activity of genes linked to critical pregnancy and health outcomes. For instance, increased methylation near the CCDC6 gene in male placentas has been associated with preterm birth, as lower activity of this gene correlates with early labor. Similarly, higher methylation near the FNDC5 gene in males results in decreased expression; this gene plays a role in producing irisin, a protein that safeguards the placenta from oxidative damage and helps regulate insulin resistance. Reduced irisin levels are tied to preeclampsia, a dangerous pregnancy complication characterized by high blood pressure.

Moreover, other genes such as ATP5MG and FAM83A—more active in female placentas—are connected to conditions like asthma, hay fever, eczema, and increased breast cancer risk later in life. Overall, male fetuses tend to grow faster and are more susceptible to pregnancy complications like preeclampsia and preterm birth, often leading to higher postnatal mortality. The research underscores the importance of sex-specific placental gene regulation in shaping both immediate pregnancy outcomes and long-term health.

This comprehensive study sheds light on the epigenetic mechanisms underlying fetal development and adult health disparities, emphasizing the need to consider fetal sex in prenatal care and future research aimed at reducing pregnancy risks. The findings were published in
Nature Communications, providing new insights into how placental gene expression influences health trajectories from birth into adulthood.

Source: MedicalXpress