Summary: A new mouse study shows that pups born to mothers who experienced prenatal stress and that were exposed at birth to the mother’s vaginal microbiota developed lower body weight and higher stress hormone levels as adults.
Source: University of Maryland
Vaginal Microbiome at Birth May Transfer Effects of Prenatal Stress to Offspring
Researchers at the University of Maryland School of Medicine report that exposing newborn mice to vaginal microbes taken from stressed mothers can reproduce several long-term effects of prenatal stress. The findings, published in Nature Neuroscience, suggest that changes to the maternal vaginal microbiota are one pathway through which maternal stress influences offspring development—particularly in males.
Microbes from the mother’s vagina colonize the newborn’s gut during delivery, and this early colonization helps shape brain development and the stress response later in life. Previous studies have shown that prenatal stress alters the composition of the vaginal microbiome and is linked to altered brain function in male offspring. What was missing until now was direct evidence that the altered vaginal microbiota can transfer those effects to offspring independently of gestational exposure.
To explore this, lead investigator Tracy Bale and colleagues collected vaginal fluid from pregnant mice that had been exposed to stress and from unstressed control mice. They then performed cesarean deliveries to produce pups that had not encountered maternal vaginal microbes at birth. Immediately after delivery, the researchers transplanted vaginal microbes from either stressed or unstressed mothers into these cesarean-born pups. The team followed the animals into adulthood to assess body growth, stress hormones, gut composition, and hypothalamic gene expression.
The study found that male pups that experienced both prenatal stress and exposure to microbiota from stressed mothers showed reduced body weight and growth and elevated stress hormone levels as adults. Importantly, transferring vaginal microbes from stressed mothers into pups that had not experienced prenatal stress reproduced some of these adult traits, indicating that the altered microbiota alone can carry effects of maternal stress. By contrast, transferring microbes from unstressed mothers into prenatally stressed pups did not fully reverse the effects of prenatal stress.
The researchers also documented changes at the molecular level. Prenatal stress altered the fetal intestinal transcriptome and intestinal niche, and those changes were associated with lasting alterations in the adult gut. Additional stress in adulthood further modified gut profiles. Maternal vaginal transfer partially mediated the effects of prenatal stress on gene expression in the hypothalamus, a key brain region that regulates stress and metabolism. Together, these results indicate that prenatal stress acts both directly on the developing fetus and indirectly by reshaping the maternal vaginal microbiome, which in turn influences offspring gut and brain development.
These mouse-model findings are relevant to human health because maternal stress during pregnancy is a known risk factor for a range of neurodevelopmental and psychiatric outcomes in children. Whether comparable microbiome-mediated mechanisms operate in humans remains an open question, but the new data highlight a biological route—early microbial colonization—that could contribute to how prenatal exposures program offspring physiology.
Dr. Bale has long studied how prenatal and parental experiences influence neurodevelopmental risk, including sex-specific effects that may raise prenatal vulnerability in males. Her earlier work has shown that maternal insults affect the placenta and fetal programming, and that paternal stress can also influence offspring by altering sperm. This broader research program supports the idea that both maternal and paternal environments leave biological marks that shape offspring health.
Source: David Kohn, University of Maryland School of Medicine
Publisher note: This summary is based on the research article “The maternal vaginal microbiome partially mediates the effects of prenatal stress on offspring gut and hypothalamus,” authored by Eldin Jašarević, Christopher D. Howard, Kathleen Morrison, Ana Misic, Tiffany Weinkopff, Phillip Scott, Christopher Hunter, Daniel Beiting & Tracy L. Bale, and published in Nature Neuroscience on July 9, 2018. DOI: 10.1038/s41593-018-0182-5.
Abstract (concise)
Early prenatal stress disrupts the maternal-to-offspring transfer of microbiota and produces lasting effects on metabolism, physiology, cognition, and behavior in male mice. Transplanting vaginal microbiota from stressed dams into cesarean-delivered pups reproduced some outcomes observed in prenatally stressed males, while transplanting control microbiota into prenatally stressed pups did not fully reverse the phenotype. Prenatal stress altered the fetal intestinal transcriptome and niche and led to adult gut changes that could be further modified by stress in adulthood. Maternal vaginal transfer partly mediated prenatal-stress effects on hypothalamic gene expression. These findings support a role for the maternal vaginal microbiome in mediating lasting consequences of prenatal stress on the gut and hypothalamus in male offspring.