Mechanisms of phthalate-induced ovarian follicle toxicity

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PROJECT SUMMARY The purpose of this application is to support the transition of Dr. Zelieann R. Craig, a postdoctoral fellow in the Department of Comparative Biosciences at the University of Illinois, into an independent research career. Dr. Craig will be mentored by Dr. Jodi A. Flaws. The main goal of this application is to provide Dr. Craig will all the technical and professional skills necessary for her to become a successful independent investigator and leader in her field. In the research training component of this proposal, Dr. Craig will investigate the mechanisms by which phthalates, a group of endocrine disrupting chemicals, cause ovarian follicle toxicity. Further, she will investigate the mechanism by which 17¿-estradiol, the major ovarian estrogen, partially prevents the effects of phthalates on ovarian follicles. Specific aim 1 will determine whether phthalates suppress growth of mouse ovarian follicles by decreasing proliferation of follicular cells. Specific aim 2 will determine whether phthalates suppress growth of mouse ovarian follicles by inducing apoptosis in follicular cells. Finally, specific aim 3 will determine the mechanism by which 17¿-estradiol prevents phthalate-induced suppression of mouse ovarian follicle growth and increased follicular death. Findings from these studies will provide basic information on the reproductive toxicity of phthalates as well as mechanisms of action for these chemicals. Thus, findings from these studies may contribute to research aimed at the discovery of potential targets for the treatment of infertility caused by environmental chemical exposure.