Mechanisms of phthalate-induced ovarian follicle toxicity

项目总结 此应用程序的目的是支持Zelieann R.Craig博士的过渡，他是 伊利诺伊大学比较生物科学系，进入了独立的研究生涯。Dr。 克雷格将接受乔迪·A·弗洛斯博士的指导。这个应用程序的主要目标是为Craig Will博士提供所有 成为一名成功的独立调查员和领导者所需的技术和专业技能 在她的领域里。在这项提案的研究培训部分，克雷格博士将通过以下方式研究机制 邻苯二甲酸酯，一组内分泌干扰化学物质，会导致卵泡毒性。此外，她还会 探讨卵巢主要雌激素--17�-雌二醇部分拮抗雌激素的作用机制 卵巢卵泡上的邻苯二甲酸盐。特定目标1将确定邻苯二甲酸盐是否会抑制小鼠的生长 通过减少卵泡细胞的增殖来抑制卵泡的生长。特定目标2将确定邻苯二甲酸酯 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 17�-雌二醇阻止邻苯二甲酸诱导的小鼠卵巢抑制机制的研究 卵泡生长和卵泡死亡增加。这些研究的结果将提供有关 邻苯二甲酸酯的生殖毒性以及这些化学物质的作用机制。因此，来自以下方面的发现 这些研究可能有助于研究旨在发现潜在的治疗靶点 由环境化学物质暴露引起的不孕不育。

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.