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.

Public Health Relevance

Relevance This project will help Dr. Zelieann Craig successfully mature into an independent researcher. Through the experiments proposed here, Dr. Craig will contribute to expanding our knowledge on the mechanisms by which phthalates affect ovarian function and cause infertility in animal models. Finally, results from this project will also contribute to research aimed at the identification of new treatments to reverse female infertility caused by environmental chemical exposure.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Heindel, Jerrold
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University of Arizona
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Rasmussen, Lindsay M; Sen, Nivedita; Liu, Xiaosong et al. (2017) Effects of oral exposure to the phthalate substitute acetyl tributyl citrate on female reproduction in mice. J Appl Toxicol 37:668-675
Rasmussen, Lindsay M; Sen, Nivedita; Vera, Jahaira C et al. (2017) Effects of in vitro exposure to dibutyl phthalate, mono-butyl phthalate, and acetyl tributyl citrate on ovarian antral follicle growth and viability. Biol Reprod 96:1105-1117
Sen, Nivedita; Liu, Xiaosong; Craig, Zelieann R (2015) Short term exposure to di-n-butyl phthalate (DBP) disrupts ovarian function in young CD-1 mice. Reprod Toxicol 53:15-22
Craig, Zelieann R; Singh, Jeffrey; Gupta, Rupesh K et al. (2014) Co-treatment of mouse antral follicles with 17?-estradiol interferes with mono-2-ethylhexyl phthalate (MEHP)-induced atresia and altered apoptosis gene expression. Reprod Toxicol 45:45-51
Craig, Zelieann R; Hannon, Patrick R; Wang, Wei et al. (2013) Di-n-butyl phthalate disrupts the expression of genes involved in cell cycle and apoptotic pathways in mouse ovarian antral follicles. Biol Reprod 88:23