First-of-its-kind research could provide key insights into fetal neurodevelopment — ScienceDaily

The study was published in the journal Molecular Psychiatry.

Antenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. The biological mechanisms underlying these associations are largely unknown, but a chemical reaction in the body in which a small molecule known as a methyl group is added to DNA, called DNA methylation, probably plays a role, according to the researchers. These findings could provide new insights into how the fetal environment potentially influences not only neurodevelopment, but also metabolism and immune functions.

More than 5,500 people participated in the study with that population divided into 12 separate cohorts, according to Anna Ruehlmann, a postdoctoral fellow in the Department of Environmental Sciences and Public Health at the UC School of Medicine and lead author of the research.

“Our study is the first to look at such a large sample size and examine the entire epigenome, so it doesn’t just look at stress control genes as in previous studies, but looks at all the epigenomic sites available right now that can study,” she says.

The research examines five separate categories of stress moms-to-be face during pregnancy. They are financial stress, conflict with a partner, conflict with a family member or friend, abuse (including physical, emotional, and mental), and death of a friend or family member, plus a cumulative score that combines all categories.

“We found that when the mother experienced a cumulative amount of stress during pregnancy, there was in fact an association with DNA methylation in cord blood, which is a kind of epigenetic modification in the developing baby in the uterus,” says Ruehlmann. . “An epigenetic modification is something that does not change the DNA sequence; however, the DNA is modified, which is something dynamic and can change in response to environmental exposures. So it is something that can be turned on or off later on.” in the child’s life or something that may not be able to do anything, it’s still unknown. It’s thought to be a gene expression control mechanism.”

Ruehlmann says that another unknown is how this process affects children once they are born.

“We found five specific DNA methylation sites with three different maternal stressors during pregnancy,” she says. “One was the cumulative stress and stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative that were associated with DNA methylation in the developing fetus. “These were occurring in genes that have been shown to be involved in neurodevelopment. The next steps are to do some functional analysis to see how these genes actually work and how DNA methylation affects their expression.”

Ruehlmann describes the process as one big puzzle.

“Epigenetic modifications are a very dynamic process, there are many changes that can occur in response to environmental factors,” he says. “You may not see the outcome of what you’re seeing biologically in early fetal development until later in a child’s development. It’s fascinating as a biologist to begin to uncover some of the biological clues about how neurodevelopment is affected during fetal development”. There are many pieces of the puzzle that have yet to be connected. It’s very exciting”.

The study’s corresponding author is Kelly Brunst of the UC Department of Environmental Sciences and Public Health. Work on this study was supported by grants T32ES010957 (Ruehlmann) and R00ES024116 and P30ES006096 (Brunst).