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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study in rats sought to 1) characterize immunoexpression of estrogen receptor alpha (ERalpha) and ERss in the efferent ducts, epididymis, and vas deferens during postnatal development; 2) establish whether ER expression changed after neonatal treatment with diethylstilbestrol (DES); and 3) determine whether ER changes coincided with abnormal epididymal/vas development. Rats were administered 10 microg DES or vehicle on days 2, 4, 6, 8, 10, and 12 and were sampled on days 10, 18, 25, 35, and 90+. At all ages, ERalpha was immunoexpressed intensely in the efferent ducts. On day 10, immunoexpression of ERalpha was absent from the epididymis and vas, but was detectable on day 18 in epithelial cells in the caput, corpus, and proximal cauda. Epithelial expression of ERalpha was absent from the distal cauda and in the proximal and distal vas was confined to a band of periductal stromal cells. Thus, on day 18, the site of ERalpha expression delineated the epididymis-vas boundary. On days 25-35, epithelial expression of ERalpha was absent, but stromal expression persisted in the vas and distal cauda. In adults, immunoexpression of ERalpha in the epididymis and vas was absent. In contrast, ERbeta was immunoexpressed in epithelial cells and some stromal cells in the efferent ducts, epididymis, and vas at all ages. In the vas, stromal expression of ERalpha and ERbeta was in different layers. DES treatment caused 1) underdevelopment of the epididymal duct and reduced epithelial height in epididymis and vas; 2) coiling of the extraepididymal vas; 3) thickening of the periductal actin-free stromal layer in the distal cauda and vas; and 4) reduced cell proliferation on day 18 in the epididymis and vas, based on incorporation of bromodeoxyuridine, especially in the epithelium. These changes coincided with abnormalities in cell- and region-specific immunoexpression of ERalpha, but not ERbeta. Thus, in DES-treated rats on day 18, epithelial expression of ERalpha occurred in all regions of the epididymis and vas instead of being confined to the caput, corpus, and proximal cauda as in controls. Similarly, stromal ERalpha expression in the vas of DES-treated rats was not confined to a periductal layer as in controls, but occurred diffusely in the muscle layer. It is suggested that 1) estrogens play a role in peripubertal development of the epididymis and vas; 2) the cellular site of expression of ERalpha either plays a role in or reflects demarcation of the epididymal/vas boundary; and 3) blurring of this boundary in DES-treated rats coincides with altered ERalpha immunoexpression.
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PMID:Age-, cell- and region-specific immunoexpression of estrogen receptor alpha (but not estrogen receptor beta) during postnatal development of the epididymis and vas deferens of the rat and disruption of this pattern by neonatal treatment with diethylstilbestrol. 1115 61

This study evaluated whether androgen action is altered in rats treated neonatally with diethylstilbestrol (DES) at a dose that induced reproductive tract abnormalities. Rats were treated on alternate days 2-12 with 10 microg DES and studied on Day 18. DES-induced abnormalities included a 70% reduction in testis weight, distension and overgrowth of the rete, distension and reduction in epithelial height of the efferent ducts, underdevelopment of the epididymal duct epithelium, reduction in epithelial height in the vas deferens, and convolution of the extra-epididymal vas. In DES-treated rats, androgen receptor (AR) immunoexpression was virtually absent from all affected tissues and the testis, whereas AR expression in controls was intense in epithelial and stromal cells. The DES-induced change in AR immunoexpression was confirmed by Western analysis for the testis. In rats treated neonatally with 1 microg DES, reproductive abnormalities were absent or minor, except for a 38% reduction in testis weight; loss of AR immunoexpression also did not occur in these rats. Treatment-induced changes in AR expression were paralleled by changes in Leydig cell volume per testis (91% reduction in the 10-microg DES group; no change in the 1-microg DES group). To test whether suppression of androgen production or action alone could induce comparable reproductive abnormalities to 10 microg DES, rats were treated neonatally with either a potent gonadotropin-releasing hormone antagonist (GnRHa) or with flutamide (50 mg/kg/day). These treatments reduced testis weight (68% for GnRHa, 40% for flutamide), and generally retarded development of the reproductive tract but failed to induce the abnormalities induced by 10 microg DES. GnRHa and flutamide caused no detectable change in AR immunoexpression in target tissues, with the exception of minor changes in the testes of flutamide-treated males. GnRHa treatment caused a reduction (83%) in Leydig cell volume comparable to that caused by 10 microg DES. Immunoexpression of estrogen receptor alpha (ER alpha) in the efferent ducts and of ER beta in all tissues studied were unaffected by any of the above treatments. Neonatal coadministration of testosterone esters (TE; 200 microg) with 10 microg DES prevented most of the morphological abnormalities induced by 10 microg DES treatment alone, though testis weight was still subnormal (46% reduction in DES + TE vs 72% in DES alone and 49% with TE alone) and some lumenal distension was still evident in the efferent ducts. Coadministration of TE with DES prevented DES-induced loss of AR immunoexpression (confirmed for testis by Western blot analysis). It is concluded that 1) reproductive tract abnormalities induced in the neonatal male rat by a high (10 microg) dose of DES are associated with reduced AR expression and Leydig cell volume; 2) these changes are largely absent with a lower dose of DES (1 microg); 3) treatments that interfere with androgen production (GnRHa) or action (flutamide) alone failed to induce reproductive tract abnormalities or alter AR expression as did 10 microg DES; 4) a grossly altered androgen:estrogen balance (low androgen + high estrogen) may underlie the reproductive tract abnormalities, other than reduced testis weight, induced by high doses of DES.
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PMID:Suppression of androgen action and the induction of gross abnormalities of the reproductive tract in male rats treated neonatally with diethylstilbestrol. 1122 7

The objective of the study was to determine the long-term effects of gestational and lactational exposure to diethylstilbestrol (DES; 0, 0.1, 1, and 10 microg/kg maternal body weight) on mouse testicular growth, epididymal sperm count, in vitro fertilizing ability, and testicular gene expression using cDNA microarrays and real-time PCR in mice on postnatal day (PND) 21, 105, and 315. In the high dose group there was a persistent decrease in the number of Sertoli cells, and sperm count was decreased on PND315 (P < 0.05). Sperm motion was unaffected; however, the in vitro fertilizing ability of epididymal sperm was decreased in the high dose group on both PND105 (P < 0.001) and PND315 (P < 0.05). Early and latent alterations in the expression of genes involved in estrogen signaling (estrogen receptor alpha), steroidogenesis (steroidogenic factor 1, 17alpha-hydroxylase/C17,20-lyase, P450 side chain cleavage, steroidogenic acute regulatory protein, and scavenger receptor class B1), lysosomal function (LGP85 and prosaposin), and regulation of testicular development (testicular receptor 2, inhibin/activin beta C, and Hoxa10) were confirmed by real-time PCR. The results demonstrate that early exposure to DES causes long-term adverse effects on testicular development and sperm function, and these effects are associated with changes in testicular gene expression, even long after the cessation of DES exposure.
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PMID:Gestational and lactational exposure of male mice to diethylstilbestrol causes long-term effects on the testis, sperm fertilizing ability in vitro, and testicular gene expression. 1213 May 71

Attempts to delineate the mechanisms of estrogen action have promoted the creation of several estrogen receptor alpha (ERalpha) mouse models in the past decade. These traditional models are limited by the fact that the receptors are either absent or present throughout all stages of development. The purpose of this work was to develop a conditional transgenic model that would provide an in vivo method of controlling the spatial and temporal regulation of ERalpha expression. The tetracycline responsive system was utilized. Three lines of transgenic mice carrying a transgene composed of the coding sequence for murine ERalpha placed under the regulatory control of a tet operator promoter (tet-op) were generated. These three lines of tet-op-mERa mice were each mated to an established line of transgenic mice expressing a tetracycline-dependent transactivator protein (tTA) from the mouse mammary tumor virus-long terminal repeat (MMTV-LTR). Double transgenic MMTV-tTA/tet-op-mERalpha mice were produced. All three lines demonstrated dominant gain of ERalpha shown by RT-PCR, immunoprecipitation, and immunohistochemistry. Transgene-specific ERalpha was expressed in numerous tissues including the mammary gland, salivary gland, testis, seminal vesicle, and epididymis. Expression was silenced by administration of doxycycline in the drinking water. This model can be utilized to evaluate the consequences of ERalpha dominant gain in targeted tissues at specific times during development. In this study dominant gain of ERalpha was associated with a reduction in epididymal/vas deferens and seminal vesicle weights consistent with the proposed action of ERalpha on fluid transport in the male reproductive tract. Combining this model with other dominant gain and gene knockout mouse models will be useful for testing effects of ERalpha action in combination with specific gene products and to evaluate if developmental and stage-specific expression of ERalpha can rescue identified phenotypes in gene knockout mice.
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PMID:Conditional over-expression of estrogen receptor alpha in a transgenic mouse model. 1221 39

The study was undertaken to identify the effect of tamoxifen on the expression and phosphorylation of motility related proteins in the adult male rats. For this purpose, tamoxifen, at a dose of 0.4 mg/kg/day, was administered per os to the male rats for a period of 60 days. Cauda sperms, epididymal fluid and tissue proteins were extracted and analyzed by electrophoresis. Testicular tissues fixed in paraffin wax were analyzed for changes in the immunoexpression of interstitial tissue estrogen receptor alpha. Phosphorylation pattern of sperm proteins was studied in vitro after incubating with 32P-ATP. The expression of dynein and tubulin in sperms, and estrogen receptors in epididymis were analyzed by immunoblotting. Tamoxifen treatment did not alter the protein profile in the cauda sperms, epididymal fluid and tissues. Endogenous phosphorylation pattern of sperm proteins in vitro was also not affected, though it is possible that 32P incorporation observed in the 66 kDa protein could be estrogen receptor. Expression of sperm dynein, tubulin and epididymal estrogen receptors was unchanged as was the expression of testicular estrogen receptors. It was concluded that tamoxifen administration alters forward motility pattern characteristic of cauda sperm without any demonstrable change in the expression or activation of motility related proteins and the phosphorylation of the sperm estrogen receptors may be involved in the regulation of sperm motility.
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PMID:Effect of tamoxifen treatment on motility related proteins in rat spermatozoa. 1289 54

The epididymis is an androgen-dependent organ that allows spermatozoa to become fully functional as they pass through this tissue. The specialized functions of the epididymis are mediated by interactions between epididymal epithelial cells and between epididymal cells and spermatozoa. Although the critical role of the epididymis in sperm maturation is well established, the mechanisms regulating cell-cell interactions remain poorly understood because of the lack of appropriate cell line models. We now report the characterization of a novel rat caput epididymal cell line (RCE) that was immortalized by transfecting primary cultures of rat epididymal cells with the simian virus 40 large T antigen. At the electron microscope level, the cell line was composed of epithelial principal cells with characteristics of in vivo cells; principal cells had well-developed Golgi apparatus, abundant endoplasmic reticulum cisternae, and few endosomes. RCE cells expressed the mRNAs coding for the androgen receptor, estrogen receptor alpha, and 4-ene-steroid-5-alpha-reductase types 1 and 2 as well as epididymal-specific markers Crisp-1 and epididymal retinoic acid binding protein. Epididymal retinoic acid binding protein expression was significantly induced with dihydrotestosterone, although this effect was not blocked by flutamide, suggesting that RCE cells are not androgen responsive. Neighboring cells formed tight and gap junctions characteristic of epididymal cells in vivo and expressed tight (occludin and claudin-1, -3, and -4) and gap junctional proteins (connexin-26, -30.3, -32, and -43). The RCE cell line displays many characteristics of epithelial principal cells, thus providing a model for studying epididymal cell functions.
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PMID:Characterization of a novel rat epididymal cell line to study epididymal function. 1609 65

The presence of steroids and their receptors throughout development, specifically androgen receptor (AR), estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta), in the epididymis of a high estrogen producing species like the stallion has not been determined. Epididymal and testicular samples were collected for analysis of testosterone and estradiol-17beta (E(2)) concentrations and for immunolocalization of AR, ERalpha and ERbeta. The concentration of testosterone in the testis and epididymis were not different among age groups (P>0.05). AR was localized in the principal cells of the caput, corpus and cauda in all four age groups. This lack of change in testosterone concentration and receptor localization suggests that testosterone is important for both development and maintenance of epididymal function. There was an age-related increase in E(2) concentrations in all regions of the epididymis (P<0.05), suggesting that E(2) is also important for adult function. ERbeta was localized in the principal cells of the caput, corpus and cauda in all four age groups, but the localization of ERalpha was regional and age dependent. In peri-pubertal animals, ERalpha immunostaining was most prominent and estradiol was similarly present in all three epididymal regions; this suggests that estradiol also plays a key role in the maturation of the stallion epididymis during the pubertal transition when sperm first arrive in the epididymis. In conclusion, these results suggest that the stallion epididymis is regulated by both androgens and estrogens throughout development and that estradiol is more important to epididymal function in the stallion than previously believed.
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PMID:Immunolocalization of estrogen and androgen receptors and steroid concentrations in the stallion epididymis. 1653 Feb 59

The steroid hormone regulation of the epididymis in a high estrogen producing animal like the boar is not currently understood. To test the hypothesis that the boar epididymis is an estrogen and androgen responsive tissue, the presence of estrogen and androgen receptors, in conjunction with steroid hormone concentrations were investigated in the boar epididymis. Epididymal (caput, corpus, cauda) and testicular samples of boars (1-2.5 years; n=5) were collected for immunolocalization of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta) and androgen receptor (AR). Concentrations of testosterone, estradiol and estrogen conjugates (EC) in the tissue were also determined. AR and ERbeta were localized in the principal and basal cells of all three epididymal regions. ERalpha was localized in the principal cells of the caput, some cells of the corpus and was not present in the cauda. Testosterone (p<0.0001), estradiol (p<0.0001) and EC (p<0.005) were significantly lower in the epididymis compared with the testis. The epididymal regions were not significantly different from each other for testosterone (p>0.15) or estradiol (p>0.09). EC were significantly higher in the corpus than either the caput (p=0.003) or cauda (p=0.002). These results suggest that the boar epididymis is responsive to both estrogens and androgens and that both steroid hormones are important for proper epididymal function. Since testosterone and estradiol concentrations are similar throughout the epididymis, regional differences in steroid hormone regulation are likely due to differences in receptor expression.
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PMID:Estrogen and androgen receptor expression in relation to steroid concentrations in the adult boar epididymis. 1703 85

The study presented herein was designed to test the hypothesis that reduced endogenous estrogen in the boar alters efferent duct morphology, epididymal morphology, and steroid receptor expression. Twenty-eight littermate pairs of boars were treated with Letrozole, an aromatase inhibitor, or with vehicle from 1 week of age until castration at 2 through 8 months. Efferent ducts and epididymides were examined for morphological development and steroid receptor expression. Efferent duct morphology was not different between control and Letrozole-treated animals at any examined age. Androgen receptor (AR), estrogen receptor alpha (ERalpha), and beta (ERbeta) were expressed in the epithelial cells of the efferent ducts at all ages; expression was similar in control and treated animals. Morphological development of the caput and corpus was delayed in Letrozole-treated animals, but this delay was transient since morphology was similar between control and treated animals at 8 months. The cauda did not show a delay in development, but was more developed in treated animals at 2 months. AR, ERalpha, and ERbeta were expressed in all three epididymal regions; no difference was observed between control and treated animals. In summary, estrogen appears to be important for development of the epididymis; however, the cauda may be regulated differently than the caput and corpus. Results for the efferent ducts suggest that the normally high endogenous estrogens are not required for regulation of fluid reabsorption in the boar. It also suggests that any ER activation required for maintenance of efferent duct morphology and function is normal in Letrozole-treated boars.
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PMID:Reduced endogenous estrogen delays epididymal development but has no effect on efferent duct morphology in boars. 1789 Feb 95

In our previous study, prenatal diethylstilbestrol (DES) exposure (days 7-21 of gestation) suppressed plasma testosterone levels and histological development in the epididymis of rat offspring. In this study, we measured cell proliferation in epididymal ductules and the expression of steroid hormone receptors and 5alpha-reductase 1 in the epididymis to assess the effect of DES on epididymal development in the offspring. Prenatal DES exposure did not alter the cell division index, but suppressed the expression of androgen receptor mRNA at 15 weeks after birth, and stimulated estrogen receptor alpha mRNA at 6 weeks. These results suggest that prenatal DES exposure results in the retardation of epididymal tissue maturation by disruption of the postnatal expression of steroid hormone receptors.
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PMID:Effects of maternal exposure to diethylstilbestrol on epididymal development in rat offspring. 1934 12


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