Estrogen, Efferent Ductules, and the Epididymis

Abstract

Estrogen's presence in the male reproductive system has been known for over 60 years, but its potential function in the epididymis remains an important area of investigation. Estrogen is synthesized by germ cells, producing a relatively high concentration in rete testis fluid. There are two estrogen receptors (ESR), the presence of which in the head of the epididymis is well documented and consistent between species; however, in other regions of the epididymis, their expression appears to be isotype, species, and cell specific. ESR1 is expressed constitutively in the epididymis; however, its presence is downregulated by high doses of estrogen, making the design of experiments complicated, as the phenotype of the Cyp19a1(-/-) mouse does not resemble that of the Esr1(-/-) mouse. Ligand-independent and DNA-binding Esr1 mutant models further demonstrate the complexity and importance of both signaling pathways in maintenance of efferent ductules and epididymis. Data now reveal the presence of not only classical nuclear receptors, but also cytoplasmic ESR and rapid responding membrane receptors; however, their importance in the epididymis remains undetermined. ESR1 regulates ion transport and water reabsorption in the efferent ducts and epididymis, and its regulation of other associated genes is continually being uncovered. In the male, some genes, such as Aqp9 and Slc9a3, contain both androgen and estrogen response elements and are dually regulated by these hormones. While estrogen pathways are a necessity for fertility in the male, future studies are needed to understand the interplay between androgens and estrogens in epididymal tissues, particularly in cell types that contain both receptors and their cofactors.

E2f4 and E2f5 are essential for the development of the male reproductive system

“…Initially, we examined the expression of Estrogen receptor 1 (ESR1) which is expressed in both ciliated and non-ciliated cells of the efferent duct epithelium and required for reabsorption of luminal fluid (reviewed in refs. 30,31 ) Our analyses showed the ESR1 was still expressed in mutant males, albeit at a slightly lower level (Fig. 4A-B).…”

“…In estrogen receptor 1 (Esr1) mutants, which display a similar phenotype in the rete testis and testis,(reviewed in 30,31 ) rete testis dilation was observed as early as postnatal day 10 38 suggesting that it may also occur prior to the stage when the seminiferous tubules are secreting fluid. Interestingly, in the Esr1 mutant mouse it was clearly established that the efferent ducts have an inability to reabsorb seminiferous tubule fluid and even secreted fluid into the lumen, 39 which could account for the observed rete testis dilation.…”

Expressional Modulation of Connexin Isoforms in the Initial Segment of Male Rat treated with Estradiol Benzoate or Flutamide

“…There is no doubt that the function and structure of epididymis are chiefly under the regulation of androgens (Robaire & Hamzeh, 2011). In addition, there are growing numbers of evidence of demonstrating the effect of estrogens on the regulation of epididymal functions (Joseph et al, 2011). Such effects of androgens and estrogens on the epididymis are exerted by modulating the expression of various genes associated with structural and functional regulation of the epididymis (Joseph et al, 2011;Robaire & Hamzeh, 2011).…”

“…In addition, there are growing numbers of evidence of demonstrating the effect of estrogens on the regulation of epididymal functions (Joseph et al, 2011). Such effects of androgens and estrogens on the epididymis are exerted by modulating the expression of various genes associated with structural and functional regulation of the epididymis (Joseph et al, 2011;Robaire & Hamzeh, 2011). Yet, the effect of steroid hormones on expression of Cx genes in the IS has not been thoroughly studied.…”

Histopathologic Effects of Anastrozole an Aromatase Enzyme Inhibitor on Rat Testicles

“…It has been observed in several articles that aromatase deficiency in mice and human also causes infertility. [16][17][18][19][20] There are plenty of endocrine, paracrine and autocrine fac- tors contributing to regulation of spermatogenesis in seminiferous epithelium. Apart from androgens, estrogens are also a potential regulator of spermatogenesis.…”