Mechanisms of phthalate-induced ovarian follicle toxicity

描述（由申请人提供） 本申请的目的是支持Zelieann R.克雷格，在伊利诺伊大学比较生物科学系博士后研究员，进入一个独立的研究生涯。 克雷格博士将由乔迪A.缺点该应用程序的主要目标是提供博士克雷格将所有必要的技术和专业技能，使她成为一个成功的独立调查员和领导者在她的领域。在本提案的研究培训部分，克雷格博士将研究邻苯二甲酸酯（一组内分泌干扰物）引起卵泡毒性的机制。此外，她将研究17-β-雌二醇（主要的卵巢雌激素）部分防止邻苯二甲酸酯对卵泡影响的机制。 具体目标1将确定邻苯二甲酸酯是否通过降低卵泡细胞增殖抑制小鼠卵泡生长。 具体目标2将确定邻苯二甲酸酯是否通过诱导卵泡细胞凋亡抑制小鼠卵泡生长。 最后，具体目标3将 确定17-β-雌二醇防止邻苯二甲酸酯诱导的小鼠卵泡生长抑制和卵泡死亡增加的机制。 这些研究的结果将提供有关邻苯二甲酸酯生殖毒性以及这些化学品作用机制的基本信息。因此，这些研究的结果可能有助于旨在发现治疗环境化学品暴露引起的不孕症的潜在靶点的研究。 公共卫生相关性：该项目将帮助Zelieann克雷格博士成功地成长为一名独立的研究人员。通过这里提出的实验，克雷格博士将有助于扩大我们对邻苯二甲酸酯影响卵巢功能和导致动物模型不育的机制的认识。 最后，该项目的结果也将有助于研究旨在确定新的治疗方法，以扭转环境化学品暴露造成的女性不育症。

DESCRIPTION (provided by applicant) 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-beta-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 growt of mouse ovarian follicles by inducing apoptosis in follicular cells. Finally, specific aim 3 will determine the mechanism by which 17-beta-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: 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.