期刊
TOXICOLOGICAL SCIENCES
卷 128, 期 1, 页码 258-271出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfs137
关键词
3-methylcholanthrene; ovary; primordial follicle; cellular survival; PI3K; Akt; mTOR signaling
类别
资金
- National Health and Medical Research Council [510735]
- Australian Research Council
- Hunter Medical Research Institute
- Newcastle Permanent Building Society Charitable Trust
- Australian Postgraduate Award PhD scholarship
3-Methylcholanthrene (3MC) is a potent ovotoxicant capable of causing premature ovarian failure through primordial follicle depletion. Despite 3MCs ovotoxicity having been established for 30 years, relatively little information exists on the mechanisms. In this study, we examined the effects of 3MC exposure on the immature ovarian follicle population. Microarray analysis revealed a complex mechanism of 3MC-induced ovotoxicity involving a number of cellular processes associated with xenobiotic metabolism, ovarian cancer, cell cycle progression, and cell death. 3MC exposure was also found to induce developing follicle atresia and aberrant primordial follicle activation via the stimulation of PI3K/Akt and mammalian target of rapamycin (mTOR) signaling pathways. Inhibition of PI3K/Akt signaling resulted in the severe depletion of the primordial follicle pool, with further analysis identifying increased Akt1-stimulated Bad phosphoinhibition in 3MC-treated primordial follicles. Our results suggest that the primordial follicle pool enters a prosurvival state upon 3MC exposure and that its depletion is due to a vicious cycle of primordial follicle activation in an attempt to replace developing follicles undergoing follicular atresia.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据