Sex differences in brain in response to midlife stress linked to fetal stress exposures

https://www.eurekalert.org/pub_releases/2021-04/mgh-sdi040121.php

 

News Release 5-Apr-2021
Exposure to inflammatory substances in the womb due to prenatal stress differentially affects stress circuitry function in male and female offspring, which is retained into midlife.
Massachusetts General Hospital

 

Men and women whose mothers experienced stressful events during pregnancy regulate stress differently in the brain 45 years later, results of a long-term study demonstrate.

In a unique sample of 40 men and 40 women followed from the womb into their mid-forties, the brain imaging study showed that exposure during fetal development to inflammation-promoting natural substances called cytokines, produced by mothers under negative stress, results in sex-associated differences in how the adult brain responds to negative stressful situations more than 45 years after birth, reports Jill M. Goldstein, PhD, founder and executive director of the Innovation Center on Sex Differences in Medicine (ICON) at Massachusetts General Hospital (MGH) and her co-authors.

The researchers found that abnormal levels of pro-inflammatory cytokines produced in mothers during pregnancy and the balance between pro-inflammatory and anti-inflammatory cytokines affect brain development differences by sex in their offspring that continue throughout life.


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For example, they found that in both sexes, lower maternal levels of tumor necrosis factor-alpha (TNFα) a pro-inflammatory cytokine, were significantly associated with higher activity in the hypothalamus, a region of the brain that, among other functions, coordinates brain activity that regulates the release of stress hormones, like cortisol.

In contrast, lower levels of TNFα were also associated with more active communication between the hypothalamus and the anterior cingulate in men only. The anterior cingulate is an area of the brain associated with impulse control and emotion.

In women only, higher prenatal exposure to interleukin-6, another inflammatory cytokine, was associated with higher levels of activity in the hippocampus, a brain region important for inhibitory control of arousal.

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