Estrogen Receptor (ER)α and ERβ Are Both Expressed in Human Ejaculated Spermatozoa: Evidence of Their Direct Interaction with Phosphatidylinositol-3-OH Kinase/Akt Pathway

Abstract

Human and animal models have evidenced how estrogen insufficiency is associated with abnormal spermatogenesis and male infertility. We previously demonstrated that estradiol is able to influence both capacitation and acrosome reaction in human ejaculated spermatozoa. It remains to be elucidated whether the biochemical changes induced by estradiol, in a rapid nongenomic way, are mediated by a single estrogen receptor (ER) or by the two ER subtypes, ER alpha and ER beta. In the present study, we have first demonstrated the concomitant expression of ER beta and ER alpha in human ejaculated spermatozoa. By RT-PCR and Southern blot, transcripts of both ERs were detected. Western blot analysis showed ER alpha and ER beta proteins at the same size as the "classical" ERs. The localization of ER alpha and ER beta with the immunocytochemistry shows a differential distribution of the two ER subtypes, the former being prevalently located in the midpiece, but the latter being in the tail. Estradiol has been associated with sperm longevity; however, the mechanism through which estradiol acts in sperm survival was never investigated. Upon estradiol exposure, we observed an enhanced phosphorylation of the proteins involved in the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway like PDK1, Akt, GSK-3, Bcl-2, together with ERK1/2, which was also involved in cell survival signals. Moreover, such phosphorylations were reduced in the presence of ICI 182, 780, addressing the role of estradiol and ERs in sperm survival. For instance we have provided, for the first time, a different interaction of the two ERs with the PI3K/Akt pathway, because ER alpha interacts with the p55 regulatory subunit of PI3K, whereas ER beta interacts with Akt1. However, it still remains to be elucidated whether the functional role of each of the ER subtypes in sperm survival signaling is redundant or distinct.

Nongenomic activation of spermatozoa by steroid hormones: Facts and fictions

“…Using mycotoxins with E-like action, Tsakmakidis et al (2006) recently reported an inhibitory effect on spontaneous boar sperm AR. Finally, Aquila et al (2004) hypothesize a role for E in human sperm survival by stimulation of the PI3K/Akt and ERK pathways. Interestingly, at difference with the other studies, this study reported inhibition of the effects by classical ER antagonists.…”

Decline of semen quality among 10 932 males consulting for couple infertility over a 20-year period in Marseille, France

“…Their activity is mediated by androgen receptors and oestrogen receptors (ERa and ERb) present on spermatozoa. [25][26][27] The conversion of androgens into oestrogens is catalysed by cytochrome P450 aromatase (P450 arom) present in Leydig cells, elongated spermatids and spermatozoa. 42,43 Many endocrine disrupting compounds are chemicals with oestrogenic or anti-androgenic activity.…”

“…Indeed, androgen and oestrogen receptors, which play critical but distinct roles in the physiology of sperm cells, are present on male germ cells. [25][26][27] Owing to regional differences in semen quality, laboratories must conduct their own local studies over certain periods of time. 28 This study's objective was to analyse sperm parameters in 10 932 male population as well as a selected sample with a total normal sperm count over a period of 20 years, from 1988 to 2007.…”

Control of Spermatogenesis in Primate and Prospect of Male Contraception

“…Estradiol should be also considered as a ''male hormone'' [3,43] and appears to be a potential germ cell survival factor in primate [2,46,62]. Aquila et al first demonstrated ER-alpha and ER-beta concomitant expression in human ejaculated spermatozoa, and suggested that estrogen may be able to influence both capacitation and acrosome reaction [2].…”

“…Aquila et al first demonstrated ER-alpha and ER-beta concomitant expression in human ejaculated spermatozoa, and suggested that estrogen may be able to influence both capacitation and acrosome reaction [2]. Estrogen receptors for both beta and alpha were present in the early meiotic spermatocytes and elongated spermatids of human testis and found that low dose of 17 beta-estradiol was capable of inhibiting germ cell apoptosis [46].…”