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Inheritable Changes Induced By Maternal Chemical Exposure

Does exposure to certain chemicals during pregnancy have the ability to affect subsequent generations?  This intriguing question was the focus of a study published last week where Crews et al. described their multidisciplinary approach examining the effects of maternal exposure to vinclozolin, a widely used fungicide, on stress sensitivity in rats three generations later (Anway et al., 2006).  Vinclozolin is already known to predispose male offspring to early disease presentation, reduce male fertility in up to four generations subsequent to exposure, as well as produce epigenetic changes in the male germ line (Anway et al., 2006).  Since vinclozolin is known to disrupt endocrine signaling, the authors sought to examine what effect this may have on the functioning of stress systems in rats.  They examined performance in behavioral anxiety tests, as well as brain metabolism and gene expression in stress reactivity-specific nuclei in the brain.

This study demonstrates that exposing a mother rat to vinclozolin during pregnancy does affect her male descendants’ anxiety levels and sensitivity to stress.  The study consisted of a line of male rats descended three generations from a vinclozolin-exposed mother rat, and a control group of unexposed rats.  Rats from each group experienced chronic restraint stress for three weeks during their adolescence, a procedure that, on its own, has been shown to cause altered emotional behaviors in adulthood (Romeo 2010) .  They found altered anxiety behavior in both groups of rats once they reached adulthood, although the results were complex.  Using the Open Field Activity test to measure anxiety behavior, they found that the control group displayed lower anxiety, spending more time in the center of the open field than rats of the vinclozolin lineage, who spent significantly more of their time in the corners of the open field, indicative of anxiety.  However, the opposite effect was seen in an additional two groups of rats who did not experience the chronic restraint stresses of the initial two groups: control-lineage rats were more stressed than vinclozolin-lineage rats.  While this is a seemingly contradictory result, the effects of epigenetic changes are far-reaching and not yet well described; behavioral phenotypes are affected by genetic changes in various parts of the brain.  Comparisons of brain metabolism in brain nuclei specific for stress reactivity, including regions of the hippocampus, showed both an effect of lineage as well as chronic stress in adolescence.  Comparison of gene networks showed alterations in many of those same brain regions.

The authors conclude that maternal exposure to an endocrine disruptor can have genetic as well as phenotypic effects on several generations of offspring – an exciting prospect for further study into epigenetics.

What do you think?

Do you study ancestral epigenetics?  Are there other chemicals that are known to affect multiple generations?  Are there different effects in females than males regarding stress reaction and behavior?

Further Reading:

Anway MD, Leathers C, Skinner MK. (2006). Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology. Dec; 147(12):5515-23.

Crews D, Gillette R, Scarpino SV, Manikkam M, Savenkova MI, Skinner MK. (2012).  Epigenetic transgenerational inheritance of altered stress responses. Proc Natl Acad Sci USA. May 21. [Epub ahead of print]

Romeo RD (2010). Adolescence: A central event in shaping stress reactivity. Dev Psychobiol 52:244–253.


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