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Thursday, May 1, 2025
The NIH findings could shed light on pregnancy complications and adult health.
What
Genes in male and female placentas show marked differences in how they are expressed, according to a study conducted by researchers at the National Institutes of Health (NIH) and other institutions. These differences involve the presence or absence of tags on DNA called methyl groups, which turn genes on or off without changing their structure. Understanding these DNA methylation patterns could inform future research on the higher risk of pregnancy complications involving male fetuses, such as stillbirth and prematurity, as well as later health problems that occur in adults born after complicated pregnancies.
The researchers analyzed male and female placental samples from a larger study to determine differences in their methylation patterns and discovered differences in gene activity between male and female placentas that could play a role in birth weight and adult disease.
The study identified 2,497 previously unreported DNA sites that exhibited different methylation patterns for males and females. Of these, and more than 2,500 sites also identified by previous studies, significant increases in methylation occurred in the DNA of male placentas in 66.9 % and in female placentas in 33.1 %. Increases in methylation in male placentas were linked to larger neonatal size, while those in female placentas were linked to larger placental size.
Some methylation increases found in male placentas were located near the gene CCDC6 . A lower activation of CCDC6 has been linked to premature birth in previous studies.
Higher methylation near the gene FNDC5 was associated with lower gene expression in male placentas, but not in female placentas. FNDC5 is involved in the production of irisin, which protects the placenta from damage caused by reactive oxygen species and insulin resistance (difficulty in cells using insulin to lower blood sugar). Lower levels of irisin have been linked to a pregnancy-related high blood pressure disorder known as preeclampsia.
Variations in genes ATP5MG And FAM83A, expressed in female placentas, have been linked to asthma, hay fever, eczema (dry, itchy, inflamed skin), and an increased risk of breast cancer later in life.
Genetic factors influence health differences between men and women, from before birth until later in life. Male fetuses grow faster that female fetuses and their pregnancies are more likely to be complicated by conditions such as preeclampsia (a hypertensive disorder of pregnancy), failure to grow at an adequate rate, and premature birth. They are also more likely to die within one year of birth. Placental dysfunction is the cause of many pregnancy complications and is considered to pave the way for health differences between men and women that occur later in life. Variations in methylation profiles are considered to be the origin of many of these differences.
The study was led by Fasil Tekola-Ayele, Ph.D., of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) from the NIH and her colleagues from other institutions. She appears in Nature Communications .Who
Fasil Tekola-Ayele, Ph.D., is available to comment on this study.
Reference
Tekola-Ayele F,
et al Sex-differentiated placental methylation and gene expression regulation have implications for neonatal traits and adult diseasesNature Communications. DOI: https://doi.org/10.1038/s41467-025-58128-3 (2025) About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD conducts research and training to understand human development, improve reproductive health, enrich the lives of children and adolescents, and maximize the capabilities of all people. For more information, visit
https://www.nichd.nih.gov .About the National Institutes of Health (NIH):
The NIH, the nation's medical research agency, comprises 27 institutes and centers and is part of the U.S. Department of Health and Human Services. The NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and investigating the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov .NIH…Transforming Discovery into Health
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