Summary: Prenatal stress can have an epigenetic impact on the future mental health of offspring. Adult children of women who experienced prenatal stress are more vulnerable to stress and other mental health disorders.
Source: Simon Fraser University
Simon Fraser University assistant professor Nadine Provençal and researchers from the Max Planck Institute of Psychiatry in Germany have identified a “cellular memory” that could help explain how fetal exposure to stress during pregnancy affects how we respond to stress exposure later in life.
“The prenatal period is one of the most dynamic and sensitive periods in a person’s life,” says Provençal.
“Prenatal stress experienced by the mother during pregnancy not only impacts the mother’s health but can also impact her developing fetus. Our research demonstrates an association between the epigenetic mark, or cellular memory, and an increased response to stress hormones, which could help to explain why some individuals are more vulnerable to stress later in life.”
Provençal and a team of researchers from around the world exposed human neurons to high levels of stress hormones, comparable to that experienced by the fetal brain during incidents of prenatal stress. The researchers observed that the developing neurons exposed to stress hormones had epigenetic marks on their genes that remained even after the stress hormones were removed. Interestingly, these epigenetic modifications also appear to act as a form of “cellular memory,” causing the mature neurons to be even more responsive to future stress.
To translate their findings from the lab to the cells of living people, the researchers studied the umbilical cord blood cells of newborns exposed to maternal stress, including maternal depression and anxiety, as well as stress hormone analogues administered to women with a risk of premature delivery. They observed a significant overlap between the epigenetic marks in neurons and those observed in the newborns’ genes exposed to maternal stress – findings that supported their earlier discovery.
Together, these findings demonstrate how prenatal stress could not only alter neurodevelopmental trajectories but also impact individual stress responses later in life. This knowledge can inform researchers about the possible long-term impact of early environmental stress exposure and help develop new ways to prevent the development of disease or mental illness earlier in life in individuals at high risk.
Simon Fraser University
Nadine Provençal – Simon Fraser University
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Original Research: Closed access
“Glucocorticoid exposure during hippocampal neurogenesis primes future stress response by inducing changes in DNA methylation”. Nadine Provençal, Janine Arloth, Annamaria Cattaneo, Christoph Anacker, Nadia Cattane, Tobias Wiechmann, Simone Röh, Maik Ködel, Torsten Klengel, Darina Czamara, Nikola S. Müller, Jari Lahti, PREDO team, Katri Räikkönen, Carmine M. Pariante, and Elisabeth B. Binder.
Glucocorticoid exposure during hippocampal neurogenesis primes future stress response by inducing changes in DNA methylation
Prenatal stress exposure is associated with risk for psychiatric disorders later in life. This may be mediated in part via enhanced exposure to glucocorticoids (GCs), which are known to impact neurogenesis. We aimed to identify molecular mediators of these effects, focusing on long-lasting epigenetic changes. In a human hippocampal progenitor cell (HPC) line, we assessed the short- and long-term effects of GC exposure during neurogenesis on messenger RNA (mRNA) expression and DNA methylation (DNAm) profiles. GC exposure induced changes in DNAm at 27,812 CpG dinucleotides and in the expression of 3,857 transcripts (false discovery rate [FDR] ≤ 0.1 and absolute fold change [FC] expression ≥ 1.15). HPC expression and GC-affected DNAm profiles were enriched for changes observed during human fetal brain development. Differentially methylated sites (DMSs) with GC exposure clustered into 4 trajectories over HPC differentiation, with transient as well as long-lasting DNAm changes. Lasting DMSs mapped to distinct functional pathways and were selectively enriched for poised and bivalent enhancer marks. Lasting DMSs had little correlation with lasting expression changes but were associated with a significantly enhanced transcriptional response to a second acute GC challenge. A significant subset of lasting DMSs was also responsive to an acute GC challenge in peripheral blood. These tissue-overlapping DMSs were used to compute a polyepigenetic score that predicted exposure to conditions associated with altered prenatal GCs in newborn’s cord blood DNA. Overall, our data suggest that early exposure to GCs can change the set point of future transcriptional responses to stress by inducing lasting DNAm changes. Such altered set points may relate to differential vulnerability to stress exposure later in life.