Effects of diethylstilbestrol on programmed oocyte death and induction of polyovular follicles in neonatal mouse ovaries
2009 Study Abstracts
The actions of estrogen are mediated by estrogen receptors (ERs) ERα (ESR1) and ERβ (ESR2). In the ovary, ESR1 is localized in interstitial and thecal cells, whereas ESR2 is localized in granulosa cells. DES can bind to both ESR1 and ESR2. In a study of Esr1 knockout (Esr1 KO) and Esr2 KO mice, it was shown that DES induced polyovular follicles by signaling through ESR2 .
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, Faslpr/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 Faslpr/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 Faslpr/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.
Our results suggest that delay or inhibition of oocyte death and an increase of Inha by DES through ESR2 may be one of the triggers for polyovular follicle formation. Although FAS system is involved in neonatal oocyte death, inhibition of oocyte death is not the only factor in induction of polyovular follicles; therefore, further studies are needed to understand the molecular mechanism of polyovular follicle formation.
- Full study (free access) : Effects of Diethylstilbestrol on Programmed Oocyte Death and Induction of Polyovular Follicles in Neonatal Mouse Ovaries, Biology of Reproduction, Volume 81, Issue 5, Pages 1002–1009 doi.org/10.1095/biolreprod.108.070599, 1 November 2009.
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