New research conducted by scientists at the National Institutes of Health (NIH) and other institutions has uncovered significant genetic differences between male and female placentas. The study, published in Nature Communications, focuses on DNA methylation patterns—chemical tags on DNA that control gene activity—providing new insights into why male fetuses are at higher risk for complications such as stillbirth, prematurity, and health problems later in life.
The Role of DNA Methylation in Placental Differences
DNA methylation involves the addition of methyl groups to DNA, which can switch genes on or off without altering the DNA sequence itself. This process is key to understanding how placental differences between males and females could influence fetal development and future health outcomes.
By analyzing male and female placental samples from a broader study, researchers identified marked differences in gene activity. The findings suggest that these differences might play a role in birth weight, pregnancy complications, and even diseases that may develop in adulthood for those born following complicated pregnancies.
Key Findings and Implications for Pregnancy Health
In total, the study identified 2,497 DNA sites with previously unreported methylation differences between male and female placentas. Among the genes with altered methylation patterns, 66.9% of the large increases were found in male placentas, while 33.1% occurred in female placentas.
Interestingly, increased methylation in male placentas was associated with larger neonatal size, while similar changes in female placentas were linked to increased placental size. These findings highlight the complex role of methylation in fetal growth and development.
The research also revealed important details about specific genes involved in pregnancy health:
CCDC6 gene: Increased methylation near this gene in male placentas was associated with lower gene activation. Previous studies have linked reduced activation of CCDC6 with preterm birth, suggesting that this gene may be crucial in the timing of labor.
FNDC5 gene: Higher methylation levels near FNDC5 in male placentas were linked to reduced gene expression, which may have implications for preeclampsia. FNDC5 is involved in the production of irisin, a protein that protects the placenta from damage caused by oxidative stress and insulin resistance. Lower irisin levels have been connected to preeclampsia, a pregnancy-related disorder characterized by high blood pressure.
ATP5MG and FAM83A genes: Methylation differences in these genes, which were found in female placentas, have been linked to an increased risk of conditions like asthma, hay fever, eczema, and breast cancer later in life.
The study underscores how genetic factors can influence male and female health outcomes from before birth to adulthood. Male fetuses are known to grow faster than females and are at higher risk for complications such as preeclampsia, intrauterine growth restriction, and preterm birth. These complications can have long-lasting effects on male health, including a higher risk of death within the first year of life.
Placental dysfunction is believed to play a significant role in these gender differences. The study suggests that variations in DNA methylation patterns, which control the activity of certain genes, may contribute to these early health disparities and influence lifelong health outcomes.
Understanding the genetic differences between male and female placentas could pave the way for more personalized approaches to pregnancy care. By identifying specific genes and methylation patterns associated with higher risk for pregnancy complications and long-term health conditions, researchers hope to develop targeted interventions that could improve outcomes for both mothers and babies.
The study was led by Fasil Tekola-Ayele, Ph.D., of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), in collaboration with other researchers. Their work highlights the importance of considering gender differences in reproductive health research and offers hope for more effective strategies to address pregnancy-related complications.
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