Researchers from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), in collaboration with other institutions, have uncovered marked differences in how genes are expressed in male and female placentas.
Published in Nature Communications in 2025, the study identifies DNA methylation patterns linked to pregnancy complications and potential adult diseases.
Sex-Based Gene Expression: A Genetic Blueprint with Lasting Impact
From the moment of conception, male and female fetuses develop differently. This study shows that even the placenta—the temporary yet vital organ supporting fetal development—expresses genes differently based on the baby’s sex.
These expression patterns are not random but shaped by DNA methylation, chemical tags that turn genes on or off without changing their structure.
Researchers analyzed placental tissue from a large dataset, discovering over 2,400 new methylation sites that differ between male and female placentas.
Combined with previously identified sites, the data points to a sex-specific molecular signature influencing how the placenta supports fetal growth and health.
Major Findings from the NIH Study
The research team identified how distinct methylation patterns influence genes critical to pregnancy outcomes.
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66.9% of large methylation increases occurred in male placentas
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33.1% were observed in female placentas
These variations may help explain why male fetuses tend to grow faster, are more vulnerable to complications like preeclampsia and preterm birth, and face higher neonatal mortality rates.
Genes Linked to Birth and Disease
Certain genes were particularly affected by sex-specific methylation:
| Gene Affected | Placental Sex | Associated Health Impact |
|---|---|---|
| CCDC6 | Male | Linked to preterm birth |
| FNDC5 | Male | Low irisin, tied to preeclampsia risk |
| ATP5MG | Female | Associated with asthma, eczema |
| FAM83A | Female | Linked to breast cancer risk |
These findings reveal that the placenta doesn’t just nourish the fetus—it also sets the stage for long-term health risks that may differ between boys and girls.
Why Methylation Matters
DNA methylation is like a dimmer switch for genes. It allows the body to fine-tune which genes are active and to what extent. In the placenta, these changes may:
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Regulate how fast the fetus grows
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Influence the placenta’s size and nutrient capacity
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Affect how the body handles stress and inflammation during pregnancy
Such regulation is essential, especially as male and female fetuses face different risks during gestation.
Understanding the Broader Health Landscape
The implications of these findings go beyond pregnancy. Conditions like hypertension, insulin resistance, and immune-related diseases have early developmental origins.
This study reinforces the developmental origins of health and disease (DOHaD) theory: the idea that events in the womb affect lifelong health.
By identifying placental gene markers linked to sex and disease, researchers may one day predict and intervene earlier in pregnancies at risk of complications.
Bottom Line
The NIH study provides compelling evidence that placental gene expression—regulated through DNA methylation—varies significantly between male and female fetuses.
These variations influence fetal growth, pregnancy complications, and possibly long-term health conditions.
Understanding these molecular differences offers a path toward more personalized and effective prenatal care.
Want to learn more about how early development shapes lifelong health?
Explore further research from the NICHD or read the full study in Nature Communications for in-depth scientific details.
Sources: National Institutes of Health.
Prepared by Ivan Alexander Golden, Founder of THX News™, an independent news organization delivering timely insights from global official sources. Combines AI-analyzed research with human-edited accuracy and context.
