Maternal stress alters placental pathways affecting fetal brain development

About one in five U.S. women experience maternal mental health conditions, and chronic stress during pregnancy can contribute to risk for both maternal and child health challenges. While researchers know this stress can increase the risk of brain and mental health disorders in children, they have not fully understood the biological mechanism involved.

Now research at The Ohio State University Wexner Medical Center has found a biological link with the placenta, which delivers oxygen and nutrients to the fetus and removes waste and carbon dioxide. Researchers found that chronic stress during pregnancy changed how the placenta communicates with the developing fetus and may affect early brain development.

Specifically, they found prenatal stress altered several placental pathways, including antiviral immune signaling, cellular energy metabolism and gene-regulatory pathways involved in chromatin, RNA processing and extracellular-matrix organization. These changes may point to mechanisms through which stress during pregnancy could influence fetal development, including pathways relevant to immune signaling, growth regulation and early brain development.

The research was recently published in Molecular Psychiatry.

The findings are quite remarkable. We found that the placenta isn't simply a passive organ. It's an active communication system between the mother and fetus. Our research suggests that stress can shift that communication in ways that may matter for brain development."

Tamar Gur, MD, PhD, endowed director of the Soter Women's Health Research Program and researcher with Ohio State's Institute for Behavioral Medicine Research and Department of Psychiatry and Behavioral Health

How the research was done

Ohio State scientists used both mice and human placentas in their research. First, they studied how stress affected the placenta and developing brain in pregnant mice. They used a method called single-cell RNA sequencing to look at what's happening inside individual cells, since the placenta is made up of different kinds of cells and each type may respond to stress differently. They also stimulated the placental cells to better understand how they reacted and what pathways were affected. The next step was to study human placentas to look for similar stress-related signals.

"In the human placentas, we saw stress-related signals that overlapped with key findings from the mouse studies, which strengthened our confidence that we were identifying biologically meaningful pathways. An unexpected finding was that prenatal stress and infection-like immune activation affected some of the same fetal-brain gene networks, but in opposite directions, suggesting that different maternal exposures may disrupt shared developmental pathways in distinct ways," Gur said.

Next steps in research

Gur's research team plans to test whether changing specific immune or energy pathways in the placenta can help protect fetal brain development during pregnancy stress or infection-like immune challenges. They also hope to eventually confirm the findings in larger human studies and learn whether the timing, intensity or length of stress changes the biological signals.

"We now know that pathways that help with stress are being altered. If we can uncover more of those pathways then maybe we can target a therapy that can help stop the transmission of stress," Gur said.

The research was funded by the National Institutes of Health and the Soter Women's Health Research Program.