Summary: A new mouse study reveals pups of mothers who faced prenatal stress and who were exposed, by birth, to maternal vaginal microbiota had decreased body weight and exhibited increased stress hormones as adults.
Source: University of Maryland.
Exposing newborn mice to vaginal microbes from stressed female mice may transfer the effects of stress to the newborns, according to a new study by researchers at the University of Maryland School of Medicine. These changes resemble those seen specifically in the male offspring of moms that were stressed during pregnancy.
The study, which will be published July 9 in the journal Nature Neuroscience, may lead to a better understanding of the way in which maternal insults such as stress affects brain development of offspring.Microbes present in vaginal fluid colonize the gut during the birth process of passing through the birth canal, and the composition of this gut microbiome influences the brain’s development and how it its responds to stress later in life. In mice, prenatal stress is known to alter the vaginal microbiota and affect male offspring’s brain function after birth, but it has not been clear how the these brain changes are caused by the altered microbiota.
Tracy Bale and her colleagues at the University of Maryland School of Medicine transplanted microbes from the vaginal fluid of either stressed or unstressed pregnant mice into both prenatally stressed and unstressed male offspring immediately after these babies were born by C-section, so were not exposed to the mother’s vaginal microbes. Dr. Bale found that the pups exposed to both stress in the womb and microbiota from stressed mothers had decreased body weights and growth and increased stress hormone levels as adults. They found that these effects could be partially reproduced in unstressed, newborn male offspring by transferring vaginal microbes from stressed mothers. Microbes from unstressed mothers, however, did not rescue the effects of stress in the womb.
These findings indicate that stress during pregnancy affects mice both directly during their gestation, in part, the team found by developmental changes to the fetal immune system, and indirectly by altering the vaginal microbiota of the mother. In humans, maternal stress during pregnancy is a risk factor for psychiatric disorders in offspring, but it remains unclear whether this risk is also influenced by the vaginal microbiota.
“These results are very intriguing,” Dr. Bale said. “It is definitely worth investigating whether the effects we found in mice also hold true in humans.”
Dr. Bale has focused much of her research on the links between stress and subsequent risk for neurodevelopmental disorders, including autism and schizophrenia. Her previous work on the placenta has found novel sex differences that may predict increased prenatal risk for disease in males.
She has previously found that, in mice, a father’s stress can affect the brain development of offspring. This stress can alter the father’s sperm, which can alter the brain development of the child. Dr. Bale has also found that male mice experiencing chronic mild stress have offspring with a reduced hormonal response to stress; this response has been linked to some neuropsychiatric disorders, including PTSD. This suggests that even mild environmental challenges can have a significant effect on the health of offspring.
Source: David Kohn – University of Maryland
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Original Research: Abstract for “The maternal vaginal microbiome partially mediates the effects of prenatal stress on offspring gut and hypothalamus” by Eldin Jašarević, Christopher D. Howard, Kathleen Morrison, Ana Misic, Tiffany Weinkopff, Phillip Scott, Christopher Hunter, Daniel Beiting & Tracy L. Bale in Nature Neuroscience. Published July 9 2018.
The maternal vaginal microbiome partially mediates the effects of prenatal stress on offspring gut and hypothalamus
Early prenatal stress disrupts maternal-to-offspring microbiota transmission and has lasting effects on metabolism, physiology, cognition, and behavior in male mice. Here we show that transplantation of maternal vaginal microbiota from stressed dams into naive pups delivered by cesarean section had effects that partly resembled those seen in prenatally stressed males. However, transplantation of control maternal vaginal microbiota into prenatally stressed pups delivered by cesarean section did not rescue the prenatal-stress phenotype. Prenatal stress was associated with alterations in the fetal intestinal transcriptome and niche, as well as with changes in the adult gut that were altered by additional stress exposure in adulthood. Further, maternal vaginal transfer also partially mediated the effects of prenatal stress on hypothalamic gene expression, as observed after chronic stress in adulthood. These findings suggest that the maternal vaginal microbiota contribute to the lasting effects of prenatal stress on gut and hypothalamus in male mice.