Estradiol Acts as a Germ Cell Survival Factor in the Human Testis in Vitro

Abstract

The necessity of estrogens for male fertility was recently discovered in studies on both estrogen receptor alpha knockout and aromatase (cyp 19 gene) knockout mice. However, direct testicular effects of estrogens in male reproduction have remained unclear. Here we studied the protein expression of ERalpha and the recently described estrogen receptor beta in the human seminiferous epithelium and evaluated the role of 17beta-estradiol, the main physiological estrogen, in male germ cell survival. Interestingly, both estrogen receptors alpha and beta were found in early meiotic spermatocytes and elongating spermatids of the human testis. Furthermore, low concentrations of 17beta-estradiol (10(-9) and 10(-10) mol/L) effectively inhibited male germ cell apoptosis, which was induced in vitro by incubating segments of human seminiferous tubules without survival factors (i.e. serum and hormones). Dihydrotestosterone, which, in addition to estradiol, is an end metabolite of testosterone, was also capable of inhibiting testicular apoptosis, but at a far higher concentration (10(-7) mol/L) than estradiol. Thus, estradiol appears to be a potent germ cell survival factor in the human testis. The novel findings of the present study together with the previously reported indirect effects of estrogens on male germ cells indicate the importance of estrogens for the normal function of the testis.

Increased Testicular Steroid Concentrations in Patients With Idiopathic Infertility and Normal FSH Levels

“…There is large augmentation of endogenous estradiol levels; consequently, estradiol/testosterone ratio was higher and may account for the deleterious effect of estradiol on the late steps of spermatogenesis, which do require testosterone [32]. If we take into account the testicular localization of the estrogen receptors (alpha and beta) that are present in both somatic cells and germ cells [37], the negative role of estradiol is conceivable. Since the testicular level of testosterone is high, it is postulated that this androgen could be further aromatized not only in Leydig cells [21] but also in Sertoli cells [17] as well as in germ cells, especially in sperm as shown in rodents [14,18,27] and in humans [24].…”

Circulating estradiol in men is inversely related to urinary metabolites of nonpersistent insecticides

“…Although estradiol is regarded as a female steroid hormone, it circulates in low but measurable levels in human males (1,2). Estradiol has recently been reported to play an important role in male reproductive health.…”

“…Estradiol is produced in the testes from aromatized testosterone, and progressive disruption of spermatogenesis and infertility was also observed among aromatase knockout mice (5). A direct role of estradiol as a germ cell survival factor was then demonstrated in the human testis in vitro, where estradiol was shown to inhibit testicular apoptosis much more effectively than testosterone (2). A potential role of nonpersistent pesticides (e.g.…”

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]. The localization of estrogen receptor beta and aromatases in pachytene spermatocytes was also demonstrated, indicating a role of estrogen in this step of spermatogenesis.…”