Exposure to environmental toxicants adversely affects human fertility. The physiological sites of action and the molecular mechanisms whereby environmental toxicants perturb human fertility are poorly understood. Studies of the environmental and genetic mechanisms of infertility suggest that aberrant development of germ cells is a major cause of human infertility. A common property of diverse environmental toxicants is the ability to perturb cellular redox homeostasis and induce oxidative stress. The first hypothesis to be tested is that oxidative stress will adversely affect germ cell development through increased apoptosis of primordial germ cells. An important response of cells to oxidative stress is induction of the oxidative stress response, which protects cells from damage caused by reactive oxygen species (ROS) produced during oxidative stress. The second hypothesis to be tested is that the protective actions of the oxidative stress response will extend to protection against apoptosis. The investigator will develop transgenic model systems to test the relationship between oxidative stress, the protective oxidative stress response, and apoptotic mechanisms important for primordial germ cell development.
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