When Emily was pregnant with her first child, she read everything she could find about fetal development. She was having a boy, and her curiosity was endless—how fast does a heart form, what influences brain growth, which foods support a healthy placenta? But what no book told her, and what many parents still don’t realize, is that the placenta—this temporary but critical organ—behaves differently depending on whether it’s nourishing a male or female fetus. It's not just a passive support system. It's an active, dynamic communicator with genetic tendencies of its own, and new research is showing us that these tendencies differ between the sexes in more ways than we imagined.
Scientists supported by the U.S. National Institutes of Health (NIH) have uncovered striking differences in how genes are expressed in male and female placentas. These differences are not about the DNA sequence itself, but rather about how it’s read—how certain genes are turned on or off through a process called DNA methylation. Imagine the genome as a vast library, and methylation as the sticky notes telling your body which books to read and which to skip. In the placental “libraries” of baby boys and girls, those sticky notes are arranged differently, and that could help explain why boys and girls sometimes arrive in the world under different circumstances—and face different health risks later in life.
Take birth weight, for instance. It’s long been observed that male newborns tend to be heavier than female ones. Now, we have a potential clue. Researchers found thousands of DNA regions—nearly 2,500 newly identified and more than 2,500 previously known—where methylation patterns differ between male and female placentas. Around 67% of these methylation increases were seen in male placentas, and the rest in female ones. What does this mean? In males, these changes were associated with bigger babies. In females, however, the methylation increases were more linked to larger placentas. This could hint at different growth strategies hardwired into each sex from the very beginning.
For parents like Emily, who spent weeks monitoring fetal size through ultrasound appointments, these findings are more than just interesting—they’re deeply relevant. Her obstetrician once explained that her son was measuring ahead in growth, but didn’t go into detail. Had she known about methylation and its role in regulating fetal development, especially in boys, the numbers might have carried a different weight—one connected to broader implications for maternal and neonatal health.
In fact, understanding methylation could even help us foresee certain pregnancy complications. One of the genes found with increased methylation in male placentas is called CCDC6. Lower activity of this gene has been previously associated with preterm birth, a complication that disproportionately affects male fetuses. Another gene, FNDC5, was found to have high methylation near its location in male placentas, correlating with lower expression of the gene. This gene is responsible for producing a hormone called irisin, which helps the placenta combat oxidative stress and insulin resistance—factors often involved in conditions like preeclampsia. Curiously, the same methylation pattern wasn’t seen in female placentas, suggesting that male placentas may be more vulnerable to disruptions in this protective system.
What does this mean for expectant mothers carrying boys? It might explain why male fetuses are more frequently affected by complications like fetal growth restriction, preterm birth, or preeclampsia. Statistically, boys grow faster in the womb and are more likely to be born early or face complications during delivery. They're also more likely to die within the first year of life. These are not just random events—they’re biological patterns that might be traced back to how the placenta functions under the influence of sex-specific epigenetics.
Even beyond birth, the echoes of these placental differences may persist. For example, in female placentas, the methylation and expression patterns of certain genes like ATP5MG and FAM83A have been linked to conditions like asthma, eczema, pollen allergies, and even the risk of developing breast cancer later in life. For families managing these conditions, it’s startling to think that the seeds may have been planted in the womb, quietly shaped by the inner workings of the placenta.
As a pediatrician, I’ve often seen well-meaning parents try to understand why one child has more frequent respiratory infections or allergic reactions than their sibling. Sometimes, the difference is blamed on daycare germs or seasonal allergies. Rarely do they consider that the placenta—a structure they left behind in the delivery room—may have played a role. But the more we understand placental methylation, the more we realize that health doesn't begin at birth. It begins long before, and it doesn’t follow the same blueprint for every child.
There’s also a growing awareness among researchers that placental health is deeply tied to adult disease. In public health, the “fetal origins” theory has gained traction, suggesting that events during pregnancy—including placental function—can influence a person’s lifelong risk of chronic illness. If a placenta favors fast fetal growth at the cost of placental resilience, as appears to be more common in male fetuses, the trade-off could mean higher risk for metabolic or cardiovascular diseases later. Conversely, a larger placenta, like those observed in many female pregnancies, might offer a different balance—possibly protecting the fetus in some ways while introducing different vulnerabilities in others.
This doesn’t mean we should start treating male and female pregnancies entirely differently, or that every parent needs to panic over epigenetics. But it does mean we should recognize that the placenta isn’t a neutral player in fetal development. It makes decisions—genetic decisions—that differ based on fetal sex, and these choices can influence not just the course of a pregnancy but the trajectory of a lifetime.
As research continues, we may soon see new ways to screen for or manage pregnancy complications that are more tailored to fetal sex. Imagine being able to predict which pregnancies are at higher risk for preeclampsia, or which babies might face metabolic issues later, based on a simple analysis of placental methylation. It’s a vision of personalized prenatal care that feels both futuristic and deeply necessary.
For now, the best takeaway for expectant parents is awareness. Whether you’re carrying a boy or a girl, remember that your baby’s placenta is doing more than just filtering nutrients. It’s shaping your child’s health in ways science is only beginning to understand. And in that understanding, we might just find better paths to prevention, intervention, and lifelong well-being.