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GENE-ENVIRONMENT INTERACTIONS: A REVIEW OF EFFECTS ON REPRODUCTION AND DEVELOPMENT
Citation:
Cummings, A M. AND R J. Kavlock. GENE-ENVIRONMENT INTERACTIONS: A REVIEW OF EFFECTS ON REPRODUCTION AND DEVELOPMENT. CRITICAL REVIEWS IN TOXICOLOGY. CRC Press LLC, Boca Raton, FL, 34(6):461-485, (2004).
Impact/Purpose:
To examine the effects of individual susceptibility to potentially adverse effects of environmental influences, such as chemical exposure, on prenatal development or male or female reproductive function
Description:
Polymorphisms in genes can lead to differences in the level of susceptibility of individuals to potentially adverse effects of environmental influences, such as chemical exposure, on prenatal development or male or female reproductive function. We have reviewed the literature in this area, with the caveat that papers involving straight gene knock-outs in experimental animals, without a clear human relevance, were largely excluded. This review represents current knowledge in this rapidly moving field, presenting both human epidemiological and animal data, where available. Among the polymorphic genes and environmental interactions discussed with respect to prenatal development are those for p-glycoprotein (multi-drug resistance protein) and the avermectins; methylenetetrahydrofolate reductase (MTHFR), an enzyme in folate metabolism, and dietary folic acid; transforming growth factor alpha (TGF ) and cigarette smoke; and alcohol dehydrogenase (ADH) and CYP2E1 in association with alcohol consumption. Effects on male reproduction attributable to gene-environment interaction involve infertility seen as a result of either OP pesticide interaction with the polymorphic paraoxonase (PON1) gene or antiandrogenic agent interaction with the androgen receptor (AR). MTHFR, folate metabolism, and dietary folic acid are also considered in conjunction with pre-eclampsia and early pregnancy loss, and the effect of the interaction of glutathione S-transferase (GST) with exposure to benzene or cigarette smoke on pregnancy maintenance is explored As a conclusion, we offer a discussion of lessons learned and suggested research needs.