Effect of controlled ovarian hyperstimulation on puberty and estrus in mice offspring
Effect of controlled ovarian hyperstimulation on puberty and estrus in mice offspring
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控制性卵巢过度刺激对小鼠子代青春期和发情期的影响
DOI：
10.1530/rep-16-0572
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发表时间：
2017-10-01
期刊：
影响因子：
3.8
通讯作者：
Zhang, Mingmin
中科院分区：
文献类型：
--
作者：
Ding, Jiahui;Tan, Xiujuan;Zhang, Mingmin
控制性超排卵（COH）被广泛用于治疗不孕症，但COH对女性后代生殖功能的长期影响目前尚不清楚。基于COH可能导致整个妊娠期女性E2水平升高，以及胎儿发育期间过量的雌激素暴露对随后的成年卵巢功能有害的事实，我们假设COH干扰雌性后代的生殖功能。为验证这一假设，采用孕马血清促性腺激素（PMSG）和HCG诱导COH小鼠产生雌性子代，观察小鼠青春期转变、血清E2、抗苗勒管激素（AMH）、FSH和LH水平、卵巢Esr 1、Amhr 2、Fshr和Lhcgr mRNA表达、卵泡数和卵巢组织学。TUNEL法检测卵泡凋亡;实时荧光定量PCR法检测Fas、FasL、Bax、Bcl 2和caspase 3、8、9的mRNA表达; Western blot法检测切割型caspase（CASP）3、8、9的蛋白表达。此外，我们进一步观察了年轻成年后代的发情周期，进行了卵泡计数，并测定了血清和卵巢中AMH的水平。COH可导致有害的妊娠结局，以及由于雌性后代卵泡的异常生长和成熟而导致的青春期转换延迟和不规则的发情周期。我们的新发现增加了新的证据，以更好地了解COH对女性后代生殖功能的潜在风险，提高了人们对COH可能对女性后代产生不利影响的认识，而不仅仅是获得更多的卵母细胞用于受精。
Controlled ovarian hyperstimulation (COH) is widely used for the treatment of infertility, while the long-term effects of COH on the reproductive function in female offspring are currently unknown. Based on the fact that COH could cause high E2 levels in women throughout pregnancy and excess estrogenic exposure during fetal development is harmful to subsequent adult ovarian function, we assumed the hypothesis that COH disrupts reproductive function in female offspring. To test this hypothesis, COH was induced in mice to obtain female offspring by pregnant mare serum gonadotropin (PMSG) and HCG, and then we evaluated pubertal transition, serum levels of E2, anti-Mullerian hormone (AMH), FSH and LH, mRNA expressions of Esr1, Amhr2, Fshr and Lhcgr in ovaries, number of follicles and ovarian histology. We also investigated the apoptosis of follicles by TUNEL; the mRNA expressions of Fas, FasL, Bax, Bcl2, and caspase 3, 8 and 9 by quantitative real-time PCR; and the protein expressions of cleaved-caspase (CASP) 3, 8 and 9 by Western blot. Moreover, we further observed estrous cyclicity in young adult offspring, performed follicle counting and measured the level of AMH in both serum and ovary. COH could induce detrimental pregnancy outcomes, as well as delayed pubertal transition and irregular estrous cycle due to the aberrant growth and maturation of follicles in female offspring. Our novel findings add new evidence to better understand the potential risks of COH on the reproductive function in female offspring, raising the awareness that COH could exert adverse effects on female offspring, rather than just obtain more oocytes for fertilization.