Clomiphene Citrate Induces ROS-Mediated Apoptosis in Mammalian Oocytes
Clomiphene Citrate Induces ROS-Mediated Apoptosis in Mammalian Oocytes作者机构：Cell Physiology Laboratory Biochemistry Unit Department of Zoology Banaras Hindu University Varanasi-221005 India Department of Reproductive Biomedicine National Institute of Health and Family Welfare New Delhi-110067 India
出 版 物：《Open Journal of Apoptosis》 (细胞凋亡（英文）)
年 卷 期：2014年第3卷第3期
页 面：52-58页
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：Clomiphene Citrate Ovulation Induction ROS Generation Apoptosis Oocyte Quality
摘 要：The clomiphene citrate (CC), a nonsteroidal triphenylethylene compound, is a first line of medicine used for the induction of ovulation in anovulatory women worldwide. In spite of high ovulation induction with the use of CC, the pregnancy rate is much lower. Such a discrepancy could be due to the peripheral anti-estrogenic effect of CC, particularly at the level of ovary, endometrium and cervical mucus. CC induces ovulation by binding to the estrogen receptors and generates hypoestrogrnic state in hypothalamus leading to release of pituitary gonadotropins. CC may have a direct effect at the level of ovary but the molecular mechanism remains unclear. Animal studies suggest that the CC induces apoptosis in granulosa cells and results hypoestrogenic state in the ovary. Reduced estradiol 17β level in the ovary affects development and maturation of oocyte leading to oocyte apoptosis. Further, CC increases hydrogen peroxide (H2O2) level and thereby bax protein expression and DNA fragmentation in cumulus-granulosa cells as well as in oocytes. The exogenous supplementation of either estradiol 17β or melatonin reduces H2O2 level in ovary, delays meiotic cell cycle progression in oocyte and protects oocyte apoptosis. Hence, supplementation of estradiol 17β or melatonin along with CC could be beneficial to protect granulosa cell as well as oocyte apoptosis and inhibit deterioration of oocyte quality. Thus, maintenance of oocyte quality may overcome the adverse effect caused due to CC treatment during infertility management.
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