Oestrogens as apoptosis regulators in mammalian testis: angels or devils?

Abstract

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.

Effects of Elevated β-Estradiol Levels on the Functional Morphology of the Testis - New Insights

“…While estradiol has been shown to have negative impacts on the testis, it has also been shown to be a potent hormone supporting germ cell survival. This dual functionality has been highlighted in the literature204647. In the patients investigated, the inhibitory effect of estradiol on spermatogenesis might be due to the estradiol induced impairment of Sertoli cell function.…”

“…Our results are also likely to provide novel concepts for treatment of males revealing excess estradiol levels. Male infertility is a condition attributed to hyperestrogenism and it has been postulated that it is more common than currently assumed4764. Up to 15% of couples are suffering from infertility and 1 in 2 of these are a result of male infertility65666768.…”

The protective effect of regucalcin against radiation-induced damage in testicular cells

“…It is well described that the cellular content within the seminiferous tubules and the proper spermatogenic output are maintained by the delicate equilibrium between cell proliferation and death [32,58]. Moreover, it is known that RGN plays an important role in the regulation of cell cycle and apoptosis [10][11][12]59].…”

Molecular approaches related to the European eel (Anguilla anguilla) reproductive process

“…The high expression levels of both GPERs at the spermatozoa stage suggests that these receptors may are mainly localized in the germ cells in the eel. Nevertheless, as GPER was shown to be localized in the Leydig and Sertoli cells, spermatogonia, spermatocytes and spermatozoa of humans, in the spermatogonia cell line of mice (Mus musculus), and in the Sertoli cells, pachytene spermatocytes and round spermatids of rats (Rattus norvegicus) (Luconi et al, 2004; reviewed by Correia et al, 2015), it can not be excluded that this may be due to Sertoli cell proliferation in the final sperm maturation process.…”

“…This suggests that GPER have differential functions during spermatogenesis depending on the teleost species. In humans, although the role of estrogens in spermatogenesis is still unclear, decreased spermatozoa numbers and motility in men who were genetically deficient in aromatase were observed, suggesting aromatase/estrogens play a role not only during the development and maintenance of spermatogenesis, but also in the final maturation of spermatozoa (Carreau et al, 2010; reviewed by Correia et al, 2015). Accordingly, studies have demonstrated the presence of sex steroid membrane receptors in human spermatozoa and have shown that the effects of estrogens and progesterone on human ejaculated spermatozoa may be mediated by GPERs and membrane progestin receptors (mPRs) respectively (Revelli et al, 1998;Luconi et al, 2004;Carreau et al, 2010).…”