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Maternal Stress Prior to Conception May Influence Genetic Expression of Offspring
Psych Progress
Maternal Stress Prior to Conception May Influence Genetic Expression of Offspring
Stephen I. Deutsch, MD, PhD
Ann Robinson Endowed Chair in Psychiatry, Professor and Chairman, Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School; Attending Psychiatrist, Sentara Norfolk General Hospital, Norfolk, Va.
First published in Psychiatry Weekly, Volume 8, Issue 23, November 18, 2013
A recent study showed that maternal prereproductive stress in rats occurring before conception and pregnancy had transgenerational effects on both newborn and adult offspring.1 Exposing female adult rats (postnatal day 45-54) to chronic unpredictable stress 14 days before they were mated resulted in increased expression of mRNA for the corticotropin releasing factor type 1 receptor (CRF1) in frontal cortex and mature oocyte of the stressed adult female rats, as well as in the brain of newborn offspring on postnatal day 0.
The data suggest that the transgenerational transmission of effects of prereproductive maternal stress occurred via changes in epigenetic regulation of CRF1 expression in ova; there was an 18.5-fold enrichment of CRF1 mRNA expression in mature oocytes of stressed adult female rats, relative to oocytes of controls.1 Changes in epigenetic regulation of gene expression occur commonly as a result of changes in the methylation status of cytosine residues in CpG islands associated with promoter regions of genes. Changes in CRF1 expression may reflect alterations of function in the hypothalamic-pituitary-adrenal (HPA) axis, which responds to stress; also, CRF1 expression is enriched in areas of brain implicated in the stress response (eg, cerebral cortex, hippocampus, and amygdala), as well as in regions of the periphery (eg, GI tract, spleen and ova).
The effects of prereproductive maternal stress on behavior of adult offspring were influenced by both gender and the history of stress exposure of the adult offspring, and particularly by the intensity of stressful exposures in adulthood. Also, expression of CRF1 mRNA in brains of adult offspring was influenced by both maternal stress history and the stress history of the adult offspring. Exposure of the adult offspring to high stress, as opposed to low stress, led to the appreciation of differences in regional expression of CRF1 mRNA between adult offspring of maternal prereproductive stressed and nonstressed dams. Differences also emerged between male and female adult offspring of stressed dams and their appropriate same-sex controls. Therefore, in the high-stress condition, adult female offspring of maternal prereproductive stressed rats showed increased expression of CRF1 mRNA in frontal cortex, compared to adult female control offspring, whereas both male and female adult offspring of maternal prereproductive stressed rats showed decreased expression in the amygdala, relative to their same-sex controls.
The implications of this research suggest that the early maternal history before conception and delivery could affect behavioral outcomes of offspring, even in adult life, independently of any interactions between the mother and her developing infant.1 The transgenerational transmission may occur through the germ line. However, transgenerational effects on outcomes may be influenced by the offspring’s gender and unique developmental history, including history of stressful exposures, and may not be dramatic. Epigenetic transmission may also include transmission of resiliency factors, and plasticity is a feature of the adult brain, so there may be reason to remain optimistic about therapeutic potential.
Disclosure: Dr. Deutsch has received grant support from the Commonwealth Health Research Board (State of Virginia).
Reference:
1. Zaidan H, Leshem M, Gaisler-Salomon I. Prereproductive stress to female rats alters corticotropin releasing factor type 1 expression in ova and behavior and brain corticotropin releasing factor type 1 expression in offspring. Biol Psychiatry. 2013;74: 680-687.