In the mammalian testis, spermatogenesis is a highly coordinated process of germ cell development, which ends with the release of ‘mature’ spermatozoa. The fine regulation of spermatogenesis is strictly dependent on sex steroid hormones, which orchestrate the cellular and molecular events underlying normal development of germ cells. Sex steroids actions also rely on the control of germ cell survival, and the programmed cell death by apoptosis has been indicated as a critical process in regulating the size and quality of the germ line. Recently, oestrogens have emerged as important regulators of germ cell fate. However, the beneficial or detrimental effects of oestrogens in spermatogenesis are controversial, with independent reports arguing for their role as cell survival factors or as apoptosis-inducers. The dual behaviour of oestrogens, shifting from ‘angels to devils’ is supported by the clinical findings of increased oestrogens levels in serum and intratesticular milieu of idiopathic infertile men. This review aims to discuss the available information concerning the role of oestrogens in the control of germ cell death and summarises the signalling mechanisms driven oestrogen-induced apoptosis. The present data represent a valuable basis for the clinical management of hyperoestrogenism-related infertility and provide a rationale for the use of oestrogen-target therapies in male infertility.

中文翻译：

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雌激素作为哺乳动物睾丸细胞凋亡调节剂：天使还是魔鬼？

在哺乳动物的睾丸中，精子发生是生殖细胞发育的高度协调过程，其以“成熟”精子的释放而告终。精子发生的精细调节严格依赖于性类固醇激素，它协调生殖细胞正常发育的细胞和分子事件。性类固醇的作用还依赖于对生殖细胞存活的控制，而凋亡导致的程序性细胞死亡已被证明是调节生殖系大小和质量的关键过程。最近，雌激素已成为生殖细胞命运的重要调节剂。然而，雌激素在精子发生中的有益或有害作用是有争议的，独立的报告认为它们作为细胞存活因子或作为细胞凋亡诱导剂的作用。雌激素的双重作用，特发性不育男性血清和睾丸内环境中雌激素水平升高的临床发现支持了从“天使到魔鬼”的转变。本综述旨在讨论有关雌激素在控制生殖细胞死亡中的作用的可用信息，并总结驱动雌激素诱导的细胞凋亡的信号传导机制。目前的数据为高雌激素相关不育症的临床管理提供了有价值的基础，并为在男性不育症中使用雌激素靶向疗法提供了理论依据。本综述旨在讨论有关雌激素在控制生殖细胞死亡中的作用的可用信息，并总结驱动雌激素诱导的细胞凋亡的信号传导机制。目前的数据为高雌激素相关不育症的临床管理提供了有价值的基础，并为在男性不育症中使用雌激素靶向疗法提供了理论依据。本综述旨在讨论有关雌激素在控制生殖细胞死亡中的作用的可用信息，并总结驱动雌激素诱导的细胞凋亡的信号传导机制。目前的数据为高雌激素相关不育症的临床管理提供了有价值的基础，并为在男性不育症中使用雌激素靶向疗法提供了理论依据。