Mechanisms of phthalate-induced ovarian follicle toxicity

项目摘要 本申请的目的是支持Zelieann R.克雷格，一个博士后研究员在 伊利诺伊大学比较生物科学系，进入独立的研究生涯。博士 克雷格将由乔迪博士指导。缺点这个应用程序的主要目标是提供博士克雷格将所有的 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。在本提案的研究培训部分，克雷格博士将通过以下方式研究其机制： 其中邻苯二甲酸盐是一组内分泌干扰物，会引起卵巢卵泡毒性。此外，她将 研究17 <$-雌二醇（主要的卵巢雌激素）部分阻止 邻苯二甲酸盐对卵泡的影响具体目标1将确定邻苯二甲酸酯是否抑制小鼠的生长 通过减少卵泡细胞的增殖来抑制卵巢卵泡。具体目标2将确定邻苯二甲酸盐是否 通过诱导卵泡细胞凋亡抑制小鼠卵泡生长。最后，具体目标3将 确定17 <$-雌二醇防止邻苯二甲酸酯诱导的小鼠卵巢抑制的机制 卵泡生长和卵泡死亡增加。这些研究的结果将提供关于 邻苯二甲酸酯的生殖毒性以及这些化学品的作用机制。因此， 这些研究可能有助于旨在发现潜在靶点的研究， 由于环境中的化学物质暴露而导致的不育症。

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.