Prenatal stress passed across generations and disrupt masculinization of the developing mouse brain

in environment, medicine, biology, omics

A new study finds that experiences in the womb can lead to individual differences in stress response that may be passed across generations.  The study shows that sons of male mice exposed to prenatal stress are more sensitive to stress as adults and these mice may have smaller testes.

The study was published in the August 17 issue of The Journal of Neuroscience.

Tracy Bale, PhD, of the University of Pennsylvania, and colleagues previously found that male mice were sensitive to stress their mothers experienced during pregnancy. In the current study Bale, together with Chris Morgan, also of the University of Pennsylvania, bred those stress-sensitive males with normal females to see if the heightened stress response could be transmitted to the next generation of mice. Even though the male offspring had no additional exposure to stress in the womb, they displayed a more pronounced reaction to stress, just like their fathers.

"This study shows that the effects of maternal stress in mice are passed by the sons to the grandsons of the stressed mothers," said Arthur Arnold, PhD, an expert on sex differences in the brain at the University of California, Los Angeles. "Since male mice are not involved in rearing the offspring in the lab setting, the findings suggest that the transmission of the trait from son to grandson is through the son's DNA," added Arnold, who was unaffiliated with the study.
However, which are the specific genes that are affected by the stress or influence downstream generations of male mice remains to be further investigated. Their study was focussed on changes in certain miRNAs and suggested that miRNAs may serve a previously unappreciated role in organizing the sexually dimorphic brain.

miRNAs (MicroRNAs) are short (RNA molecules of about 22 nucleotides long and are considered post-transcriptional regulators as they bind to complementary sequences on target messenger RNA resulting in its degradation.

In general, female mice tend to respond more to stress than do males. However, in the current study, the sons and grandsons of female mice that were stressed while pregnant showed a stress response more similar to female mice.

Compared with other male mice, the stress-sensitive grandsons also had smaller testes, as did their fathers, suggesting they were exposed to less testosterone around birth — a critical period for establishing sex differences in the brain. Additionally, genes involved in brain development were turned on and off in a pattern more similar to female than male mice.

"Together these findings suggest prenatal stress may disrupt masculinization of the developing mouse brain," Bale said. Although such changes did not deter the stress-sensitive male mice from reproducing, the results suggest exposure to stress during early pregnancy can lead to long-term changes in offspring that can be passed across generations.

Further, according to authors, their  data support the existence of a sensitive period of early gestation when epigenetic programming of the male germline can occur, permitting transmission of specific phenotypes into subsequent generations.

Source article:  Early Prenatal Stress Epigenetically Programs Dysmasculinization in Second-Generation Offspring via the Paternal Lineage. Christopher P. Morgan andTracy L. Bale  The Journal of Neuroscience, 17 August 2011, 31(33):11748-11755; doi:10.1523/JNEUROSCI.1887-11.2011

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