Summary: DHA supplements have long been recommended for pregnant women to assist in healthy fetal development. A new study finds DHA supplements can also reverse the impact of early prenatal stress on developing male babies.

Source: University of Missouri Columbia

Neurodevelopmental disorders like autism and schizophrenia disproportionately affect males and are directly linked to early life adversity caused by maternal stress and other factors, which might be impacted by nutrition. But the underlying reasons for these male-specific impacts are not well understood.

Researchers from the University of Missouri School of Medicine and the MU Thompson Center for Autism and Neurodevelopmental Disorders have uncovered possible reasons for male vulnerability in the womb, and they’ve learned a specific maternal dietary supplement called docosahexanoic acid (DHA) may guard against the impact of maternal stress on unborn males during early development.

“We believe differences in metabolic requirements for male and female embryos as early as the first trimester, combined with dynamic differences in the way the male and female placenta reacts to environmental factors, contributes to the increased risk for male neurodevelopmental disorders later in life,” said senior author David Beversdorf, MD, a professor of radiology, neurology and psychology at MU.

Beversdorf worked with principal investigator Eldin Jašarevic, PhD, an assistant professor of pharmacology at the University of Maryland School of Medicine and a team of researchers on the study which involved grouping 40 mice into four different cohorts.

In the DHA groups, they found the supplement reversed the impact of EPS on males. Image is in the public domain

Group 1 mothers received a standard diet and were not exposed to any early prenatal stress (EPS). Group 2 got the standard diet while being exposed to (EPS), which consisted of restraint, light, noise and predator threat. Group 3 got a diet modified with supplemental DHA but was not exposed to EPS. Group 4 received DHA supplementation and EPS.

The team analyzed the embryos and placentas at 12.5 days of gestation and found exposure to prenatal distress decreased placenta and embryo weight in males but not females. In the DHA groups, they found the supplement reversed the impact of EPS on males.

“This study yielded two results regarding the interaction between maternal stress and dietary DHA enrichment in early stage embryos,” Beversdorf said.

“First, stress on the mother during the first week of gestation appeared to influence gene expression pattern in the placenta, and the gender of the offspring determined the magnitude of disruption. Second, a maternal diet enriched with preformed DHA during periods of high stress showed partial rescue of stress-dependent dysregulation of gene expression in the placenta.”

Beversdorf said future studies will be needed to better understand the complex cellular and molecular mechanisms linking maternal diet consumption, chronic stress during pregnancy, placental gene expression and lasting health outcomes in offspring.

In addition to Beversdorf and Jašarevic, the study authors include University of Missouri colleagues Kevin Fritsche, PhD, professor of nutrition and exercise physiology; David Geary, PhD, professor of psychology; and Rocio Rivera, PhD, associate professor of animal science.

The study, “Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress,” was recently published in the journal Biology of Sex Differences.

Funding: Research reported in these publications was supported by grants from the University of Missouri Research Board, F21C-Nutrition for Health Group, F21C-Reporductive Biology Group and the School of Medicine Mission Enhancement Fund.

Beversdorf has consulted with Quadrant Biosciences, Impel Pharma, YAMO Pharma and Staliclca, unrelated to this work.

The content is solely the responsibility of the authors and does not necessarily represent the views of the funding agencies.

About this neurodevelopment and stress research news

Source: University of Missouri Columbia
Contact: Eric Maze – University of Missouri Columbia
Image: The image is in the public domain

Original Research: Open access.
“Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress” by David Beversdorf et al. Biology of Sex Differences


Abstract

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Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress

Early life adversity is widely recognized as a key risk factor for early developmental perturbations and contributes to the presentation of neuropsychiatric disorders in adulthood. Neurodevelopmental disorders exhibit a strong sex bias in susceptibility, presentation, onset, and severity, although the underlying mechanisms conferring vulnerability are not well understood. Environmental perturbations during pregnancy, such as malnutrition or stress, have been associated with sex-specific reprogramming that contribute to increased disease risk in adulthood, whereby stress and nutritional insufficiency may be additive and further exacerbate poor offspring outcomes.

To determine whether maternal supplementation of docosahexanoic acid (DHA) exerts an effect on offspring outcome following exposure to early prenatal stress (EPS), dams were fed a purified 10:1 omega-6/omega-3 diet supplemented with either 1.0% preformed DHA/kg feed weight (DHA-enriched) or no additional DHA (denoted as the control diet, CTL). Dams were administered chronic variable stress during the first week of pregnancy (embryonic day, E0.5–7.5), and developmental milestones were assessed at E 12.5. Exposure to early prenatal stress (EPS) decreased placenta and embryo weight in males, but not females, exposed to the CTL diet. DHA enrichment reversed the sex-specific decrease in placenta and embryo weight following EPS.

Early prenatal exposure upregulated expression of genes associated with oxygen and nutrient transport, including hypoxia inducible factor 3α (HIF3α), peroxisome proliferator-activated receptor alpha (PPARα), and insulin-like growth binding factor 1 (IGFBP1), in the placenta of CTL diet males exposed to EPS. DHA enrichment in EPS-exposed animals abrogated the male-specific upregulation of PPARα, HIF3α, and IGFBP1.

Taken together, these studies suggest that maternal dietary DHA enrichment may buffer against maternal stress programming of sex-specific outcomes during early development.



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