Localization of Androgen and Estrogen Receptors in Adult Male Mouse Reproductive Tract

Abstract

There is considerable variation, both within and between species, in reports of nuclear steroid receptor localizations in the male reproductive tract. In this study, androgen receptor (AR) and estrogen receptors ERα and ERβ were visualized by immunohistochemistry in adult male mice reproductive tracts, including testes, efferent ductules; initial segment, caput, corpus, and cauda epididymides; and vas deferens. Antibody specificity was demonstrated by Western blot and antibody competition. In testis, AR was expressed in Leydig cells, Sertoli cells, and most peritubular cells, but not in germ cells; Sertoli cells showed more intense staining in stages VI‐VII; ERα was present in Leydig and some peritubular cells; ERβ was in Leydig, some peritubular, all Sertoli and germ cells except in spermatids and meiotic spermatocytes. In efferent ductules, AR was strongly expressed in ciliated and nonciliated epithelial cells and in stromal cells; ERα was strongly expressed in ciliated and nonciliated epithelial cells; stromal cells were negative; and ERβ was strongly expressed in ciliated and nonciliated epithelial cells and also in stromal cells. In epididymis, AR was strongly expressed in all epithelial cells (not in intraepithelial lymphocytes); ERα was strongly expressed in apical, narrow, and some basal cells of the initial segment, and in caput, principal cells of the caput, clear cells of the distal caput through cauda; stromal cells were negative in the initial segment, but more stromal cells were stained from caput to cauda; ERβ was strongly expressed in most of epithelial cells of the epididymis, but stromal cells were inconsistently stained. In vas deferens, AR was weakly expressed or absent in principal cells but moderately stained in basal cells, smooth muscle cells of stroma were stained intensely, ERα was absent in epithelial cells but present in a subepithelial smooth muscle layer, and ERβ was strongly expressed in all epithelial cells and most stromal cells. This study demonstrates that the reproductive tracts of male mice differ considerably from those of rats in expression of ARs and ERs and that caution is needed when extrapolating nuclear steroid receptor data across mammalian species.

G Protein-Coupled Estrogen Receptor (GPER) and ERs Are Modulated in the Testis–Epididymal Complex in the Normal and Cryptorchid Dog

“…In particular, the presence of GPER in pachytene spermatocytes and round spermatids could be hypothesized to be related to an activation of the epidermal growth factor receptor/extracellular signal-regulated kinases (EGFR/ERK) pathway, which is involved in the transcriptional modulation of genes controlling apoptosis and differentiation [ 25 , 26 ]. For ERs’ localization, it was reported that ER-alpha and ER-beta are expressed in the testicular germ cells in some animal species including dogs, rodents, and humans, with some differences in their protein distribution [ 32 , 34 , 35 , 46 , 47 ]. According to our findings, GPER is co-expressed only with ER-alpha in round spermatids, suggesting their involvement in the regulation of spermiogenesis, while the localization of ER-beta in Sertoli cells supports germ cell maturation through the supply of different mediators including estrogens, which could be indicative of this function in these cells.…”

“…As known, estrogens have an important role in maintenance of some aspects of epididymal physiology [ 14 ]. The expression of ERs has been widely documented in the epididymis of several species (mice, rats, dogs, cats, and monkeys) [ 32 , 35 , 36 , 46 , 58 ] with a common observation of the presence of ER-alpha in the efferent ductules that not only provide to the reabsorption of more than 90% of the rete testis fluid but concentrate sperm for epididymal storage [ 59 ]. In addition, the very wide GPER expression in the epididymis of pigs [ 28 , 60 ], rats [ 30 ], sheep [ 61 ] and in humans’ ductuli efferents and proximal epididymis [ 29 ] suggests its involvement in sperm maturation, protection, and storage.…”

Steroidogenesis and androgen/estrogen signaling pathways are altered inin vitromatured testicular tissues of prepubertal mice

“…Several estrogen receptors mediate the effects of estrogens in the testis. In rodents, ERα was found in Leydig cells and peritubular myoid cells, ERβ was found in Sertoli cells and some germ cells (spermatogonia, spermatocytes) and GPER was detected in Leydig cells, Sertoli cells and germ cells (spermatocytes, spermatids) (37)(38)(39)(40)(41). Faah, encoding a hydrolase that promotes Sertoli cell survival by degrading anandamide, is a direct target gene of estrogens in mature Sertoli cells (42,43).…”

Steroidogenesis and androgen/estrogen signaling pathways are altered in in vitro matured testicular tissues of prepubertal mice

“…Several estrogen receptors mediate the effects of estrogens in the testis. In rodents, ERα was found in Leydig cells and peritubular myoid cells, ERβ was found in Sertoli cells and some germ cells (spermatogonia, spermatocytes), and GPER was detected in Leydig cells, Sertoli cells, and germ cells (spermatocytes, spermatids) (Zhou et al, 2002;Kotula-Balak et al, 2018;Lucas et al, 2010;Chimento et al, 2010;Chimento et al, 2011). Faah, encoding a hydrolase that promotes Sertoli cell survival by degrading anandamide, is a direct target gene of estrogens in mature Sertoli cells (Grimaldi et al, 2012;Rossi et al, 2007).…”