Effects of Diethylstilbestrol on Programmed Oocyte Death and Induction of Polyovular Follicles in Neonatal Mouse Ovaries
Effects of Diethylstilbestrol on Programmed Oocyte Death and Induction of Polyovular Follicles in Neonatal Mouse Ovaries
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DOI：
10.1095/biolreprod.108.070599
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发表时间：
2009-11-01
影响因子：
3.6
通讯作者：
Sato, Tomomi
中科院分区：
文献类型：
--
作者：
Kim, Hannah;Nakajima, Tadaaki;Sato, Tomomi
在小鼠中，新生儿暴露于合成雌激素己烯雌酚（DES）诱导多卵卵泡，每个卵泡含有两个或更多个卵母细胞。我们先前报道了雌激素受体β（ESR 2）介导DES信号在多卵卵泡诱导。然而，多卵卵泡诱导的具体机制尚未阐明。啮齿类动物的卵泡发生在出生后不久就开始了，伴随着卵母细胞的程序性死亡和生殖细胞的丢失。在这项研究中，DES对卵母细胞死亡和被认为参与多卵卵泡诱导的基因的mRNA表达的影响进行了分析，在C57 BL/6 J，Fas（lpr/lpr）（缺乏细胞死亡受体，FAS）和Esr 2敲除（Esr 2 KO）小鼠的卵巢卵泡发生的关键时期。新生儿DES暴露降低了C57 BL/6 J小鼠的程序性卵母细胞死亡;然而，在Esr 2 KO小鼠中未观察到这种降低。对照组Fas（lpr/lpr）小鼠卵母细胞凋亡指数显著低于对照组C57 BL/6 J小鼠。而对照组20日龄Fas（lpr/lpr）小鼠多卵卵泡发生率与对照组C57 BL/6 J小鼠相似。此外，DES暴露改变了2日龄C57 BL/6 J小鼠中的α-干扰素（Inha）的mRNA表达。这些结果表明，DES通过ESR 2抑制卵母细胞死亡可能是多卵卵泡诱导的触发因素之一。FAS系统也参与新生卵母细胞死亡;然而，减少卵母细胞死亡不足以诱导多卵卵泡。DES通过ESR 2增加小鼠卵巢中Inha mRNA和减少卵母细胞死亡的组合可能与多卵卵泡诱导相关。
In mice, neonatal exposure to a synthetic estrogen, diethylstilbestrol (DES), induces polyovular follicles, which contain two or more oocytes per ovarian follicle. We reported previously that the estrogen receptor beta (ESR2) mediates DES signaling in polyovular follicle induction. However, the specific mechanism of polyovular follicle induction has not yet been clarified. Folliculogenesis in rodents begins soon after birth, accompanied by programmed oocyte death and germ cell loss. In this study, the effects of DES on oocyte death and on mRNA expression of genes thought to be involved in polyovular follicle induction were analyzed during a crucial period of folliculogenesis in the ovary of C57BL/6J, Fas(lpr/lpr) (lacking cell death receptor, FAS), and Esr2 knockout (Esr2 KO) mice. Neonatal DES exposure reduced programmed oocyte death in C57BL/6J mice; however, this reduction was not observed in Esr2 KO mice. In control Fas(lpr/lpr) mice, the oocyte apoptotic index was significantly lower than that in the control C57BL/6J mice. However, the polyovular follicle incidence in control 20-day-old Fas(lpr/lpr) mice was similar to that in the control C57BL/6J mice. Moreover, DES exposure changed mRNA expression of inhibin-alpha (Inha) in 2-day-old C57BL/6J mice. These results suggest that inhibition of oocyte death by DES through ESR2 may be one of the triggers for polyovular follicle induction. The FAS system is also involved in neonatal oocyte death; however, reduction of oocyte death is not sufficient for polyovular follicle induction. The combination of increased Inha mRNA and reduction of oocyte death in the ovaries of mice by DES through ESR2 might be correlated with polyovular follicle induction.