Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reproductive tissues were collected monthly from male Antechinus stuartii during the first 5 months of post-partum development, a period corresponding to the time between birth and the initial increase in plasma androgen above non-detectable levels. The gonad appeared undifferentiated at day 3 after birth, but the basic structure of the testis (tunica albuginea, sex cords, stroma) was well established at 1 month of age. At this stage the developing sex cords contained a single layer of pre-Sertoli cells which surrounded a central core of gonocytes. Mitotic division of cells within the cords was common. Intertubular fetal Leydig cells, often observed in clumps, and perivascular and peritubular fetal Leydig cells were common and readily identified. By 2 months of age there was an obvious increase in cord diameter and the abundance of pre-Sertoli cells, while a marked reduction in the density of connective tissue cells and fetal Leydig cells was observed in the interstitium. Fetal Leydig cells appeared to persist only in close association with the developing seminiferous cords. Testicular size and the diameter and convolutions of the seminiferous cords increased substantially (two fold increase in cord diameter) by 3 months of age. Gonocytes had begun to migrate toward the basal lamina of the cords, and connective tissue cells and Leydig cells appeared in large numbers throughout the interstitium. By 4 and 5 months of age, gonocytes were commonly seen in contact with the basement membrane, and the cords remained non-patent. Leydig cell number and density increased greatly during these months. The epididymal epithelium remained undifferentiated throughout the first 5 months of development. Epithelial cells characteristically contained a large nucleus which occupied most of the cell, very little cytoplasm and few organelles. The diameter of the epididymal duct was similar throughout for the first 3 months of the study. In months 4 and 5 the diameter of the duct in caput and corpus regions increased, ahead of that of the cauda, possibly in relation to variations in androgen exposure at different regions along the developing duct. Further histological and quantitative studies on the growth and development of Leydig cells within the Dasyuridae are needed for comparison with eutherian mammals, which together with knowledge of the changing levels of fetal androgens may provide a greater understanding of the role of the different populations of Leydig cells in the differentiation of the testis and male reproductive tract.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Testicular and epididymal development in the brown marsupial mouse, Antechinus stuartii (Dasyuridae, Marsupialia). 821 26

We evaluated the effects of chronic renal failure (CRF) on testicular function and semen physiology. A CRF model was created in 48 male rats by performance of five-sixths nephrectomies in two-stage procedures, and a control (group A) by two-stage sham operation on six male rats. Seven weeks later, serum urea and creatinine concentrations were assessed, and the nephrectomized rats were then equally divided into four groups, B, C, D and E, and treated with saline, erythropoietin, bromocryptine and hydralazine, respectively. Seventeen weeks after the first surgical procedure, the number of fertile rats, the mean values of epididymal sperm content and motility, the outcome of in vitro fertilization, and peripheral serum testosterone concentrations and responses to human chorionic gonadotropin were significantly higher (P < 0.05) in groups A, C and D than in groups B and E. Serum prolactin concentration was significantly higher (P < 0.05) in all groups of nephrectomized rats than in group A. Our results indicate that bromocryptine and erythropoetin improve Leydig cell function, spermatogenesis epididymal sperm maturation, and sperm fertilizing capacity in rats with CRF.
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PMID:Effects of erythropoietin, bromocryptine and hydralazine on testicular function in rats with chronic renal failure. 919 18

Previous studies have shown that macrophages and their cytokine products, particularly interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha), regulate testicular Leydig cell steroidogenesis in vitro and in vivo. However, the data concerning IL-1 have been somewhat contradictory, showing both inhibitory and stimulatory effects of IL-1 depending on the experimental conditions. In the present studies, mice lacking a functional type I IL-1 receptor (IL-1R]; the only IL-1 receptor subtype capable of IL-1-induced signal transduction) were used to examine the role of this cytokine in vivo. The data show that the absence of IL-1 signal transduction has no effect on steroidogenic enzyme concentrations within the Leydig cells, and the males have normal serum testosterone concentrations. Moreover, epididymal sperm numbers are normal in IL-1RI nullizygous males in contrast to recent reports of a role for IL-1 in germ cell proliferation and DNA synthesis. Taken together these observations suggest that IL-1 signalling is not essential for Leydig cell function or spermatogenesis in vivo and highlight the need to reassess many of the current methods of experimental approaches for examining cytokine function in vitro.
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PMID:Normal sexual function in male mice lacking a functional type I interleukin-1 (IL-1) receptor. 944 61

Glutathione S-transferases (GSTs), a family of isoenzymes, catalyze the conjugation of glutathione to a variety of electrophiles, and protect cellular constituents from electrophilic and oxidative attack. Aging is associated with an overall increase in oxidative stress and thus free radical production. The present study examines the immunocytochemical localization of Ya, Yc, Yb1, Yb2, Yo, and Yf GST subunits in the testis and epididymis of Brown Norway rats aged 3, 12, 18, and 24 months. In the testis, neither Sertoli nor germ cells showed changes in the GST staining pattern during aging. At 24 months, two types of Leydig cells were noted. Some (peritubular) formed a distinct band at the periphery of the tubule while others were seen in the interstitial space. The peritubular cells were identified as Leydig cells by specific staining for 3beta-hydroxysteroid dehydrogenase (3beta-HSD), a Leydig cell-specific marker. Both types of Leydig cells were intensely reactive for all GST subunits at all ages. In the epididymis, principal cells of all epididymal regions, except the proximal cauda region, showed no changes in GST expression at all ages examined. At 24 months, some principal cells of this region became greatly enlarged and vacuolated. These cells were unreactive for Yo, Yb1, Yb2, and Yc, while adjacent normal-appearing principal cells maintained the same intensity of expression as seen in 3-month controls. In contrast, vacuolated principal cells were reactive for the Ya subunit, while adjacent normal principal cells were unreactive. These data indicate that selective changes occur in the expression of GSTs at 24 months in principal cells having both a normal and a vacuolated appearance. The underlying mechanism responsible for these changes with age is unresolved, but we speculate that they lose the ability to handle oxidative stress. Taken together, these data show that aging affects region-specific changes in GST expression in the epididymis and Leydig cell distribution in the testis.
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PMID:The effects of aging on the expression of glutathione S-transferases in the testis and epididymis of the Brown Norway rat. 973 48

The objective of this study was to evaluate morphological characteristics and testicular function of boars with different endogenous concentrations of FSH. Boars were selected at 6 mo of age on the basis of mean FSH concentrations in plasma collected at 4, 5, and 6 mo of age. Boars were classified within half-sibling families based on whether they had high concentrations of FSH (HiFSH, > 500 ng/ml, n = 9) or low concentrations (LoFSH, < 500 ng/ml, n = 7). At 14.5 mo, testes were collected, fixed, sectioned at 1 microm, and evaluated for morphological characteristics. Boars with LoFSH had larger (p < 0.01) testicular and epididymal weights than boars with HiFSH, greater (p < 0.01) daily sperm production per gram of testis, and greater total daily sperm production per boar. Testes of boars with LoFSH had a greater (p < 0.03) volume percentage of seminiferous tubules, a lesser percentage (p < 0.03) of Leydig cells, and a somewhat lesser (p = 0.06) percentage of vascular structures than testes of boars with HiFSH. Testes of boars with LoFSH had greater (p < 0.01) total tubule volume and tubule length than testes of boars with HiFSH. There were no differences (p > 0.70) in volume, diameter, or total number of Leydig cells or in total interstitial volume in testes (p > 0.41) of these two groups. Production of testosterone in vitro per paired testis and per million Leydig cells was not different (p > 0.65) between boars with HiFSH or LoFSH. Greater concentrations of FSH in blood plasma were negatively associated with development of seminiferous tubules and spermatogenic efficiency, whereas Leydig cell development was not different in boars of these two groups.
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PMID:Testicular morphology and function in boars differing in concentrations of plasma follicle-stimulating hormone. 985 94

Antiandrogenic chemicals alter sexual differentiation by a variety of mechanisms, and as a consequence, they induce different profiles of effects. For example, in utero treatment with the androgen receptor (AR) antagonist, flutamide, produces ventral prostate agenesis and testicular nondescent, while in contrast, finasteride, an inhibitor of 5 alpha-dihydrotestosterone (DHT) synthesis, rarely, if ever, induces such malformations. In this regard, it was recently proposed that dibutyl phthalate (DBP) alters reproductive development by a different mechanism of action than flutamide or vinclozolin (V), which are AR antagonists, because the male offsprings display an unusually high incidence of testicular and epididymal alterations--effects rarely seen after in utero flutamide or V treatment. In this study, we present original data describing the reproductive effects of 10 known or suspected anti-androgens, including a Leydig cell toxicant ethane dimethane sulphonate (EDS, 50 mg kg-1 day-1), linuron (L, 100 mg kg-1 day-1), p,p'-DDE (100 mg kg-1 day-1), ketoconazole (12-50 mg kg-1 day-1), procymidone (P, 100 mg kg-1 day-1), chlozolinate (100 mg kg-1 day-1), iprodione (100 mg kg-1 day-1), DBP (500 mg kg-1 day-1), diethylhexyl phthalate (DEHP, 750 mg kg-1 day-1), and polychlorinated biphenyl (PCB) congener no. 169 (single dose of 1.8 mg kg-1). Our analysis indicates that the chemicals discussed here can be clustered into three or four separate groups, based on the resulting profiles of reproductive effects. Vinclozolin, P, and DDE, known AR ligands, produce similar profiles of toxicity. However, p,p'-DDE is less potent in this regard. DBP and DEHP produce a profile distinct from the above AR ligands. Male offsprings display a higher incidence of epididymal and testicular lesions than generally seen with flutamide, P, or V even at high dosage levels. Linuron treatment induced a level of external effects consistent with its low affinity for AR [reduced anogenital distance (AGD), retained nipples, and a low incidence of hypospadias]. However, L treatment also induced an unanticipated degree of malformed epididymides and testis atrophy. In fact, the profile of effects induced by L was similar to that seen with DBP. These results suggest that L may display several mechanisms of endocrine toxicity, one of which involves AR binding. Chlozolinate and iprodione did not produce any signs of maternal or fetal endocrine toxicity at 100 mg kg-1 day-1. EDS produced severe maternal toxicity and a 45% reduction in size at birth, which resulted in the death of all neonates by 5 days of age. However, EDS only reduced AGD in male pups by 15%. Ketoconazole did not demasculinize or feminize males but rather displayed anti-hormonal activities, apparently by inhibiting ovarian hormone synthesis, which resulted in delayed delivery and whole litter loss. In summary, the above in vivo data suggest that the chemicals we studied alter male sexual differentiation via different mechanisms. The anti-androgens V, P, and p,p'-DDE produce flutamide-like profiles that are distinct from those seen with DBP, DEHP, and L. The effects of PCB 169 bear little resemblance to those of any known anti-androgen. Only in depth in vitro studies will reveal the degree to which one can rely upon in vivo studies, like those presented here, to predict the cellular and molecular mechanisms of developmental toxicity.
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PMID:Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p'-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. 1018 94

Piperine was administered to mature male albino rats at doses of 5 and 10 mg/kg body weight, p.o., respectively, for 30 days. Only a 10 mg dose of piperine treatment caused a significant reduction in the weights of testis and accessory sex organs. Histological studies revealed that piperine at a 5 mg dose caused partial degeneration of germ cell types, whereas at a 10 mg dose, it caused severe damage to the seminiferous tubule, decrease in seminiferous tubular and Leydig cell nuclear diameter and desquamation of spermatocytes and spermatids. Correlated to the structural changes, a fall in caput and cauda epididymal sperm concentrations was also evident. A 10 mg dose of piperine also caused a marked increase in serum gonadotropins and a decrease in intratesticular testosterone concentration, despite normal serum testosterone titres.
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PMID:Effects of piperine on testis of albino rats. 1036 36

A variety of active diterpene epoxides, including the triptolide (isolated from Tripterygium wilfordii) have been reported to cause infertility in male rats. Previously, we showed that oral administration of triptolide at a dosage of 100 microg/kg per body weight for 70 days completely inhibited fertility in male rats, with little or no demonstrable detrimental effect on spermatogenesis and Leydig cell function as determined by testicular light microscopic appearance and serum and intratesticular testosterone levels. Despite the apparent absence of effects on the testes, cauda epididymal sperm were abnormal, with complete cessation of sperm motility and some reduction in sperm numbers. This study was undertaken to provide additional insight into the subcellular sites and possible mechanisms of action of this compound using ultrastructural analysis of the testes and epididymidis. The most striking effect of triptolide treatment was observed in sperm in the epididymis. In rats rendered infertile with 100 microg/kg per body weight of triptolide daily for 70 days, virtually all cauda epididymal sperm exhibited complete absence of plasma membrane over the entire middle and principal piece, premature decondensation of the nuclei, and disorganization of the mitochondrial sheath with many vacuolated mitochondria. No ultrastructural differences in the epididymal epithelium were observed between control and triptolide-treated rats. The testes appeared to be mildly affected after triptolide treatment but exhibited only subtle ultrastructural defects in the germ cells. The findings of severe impairment of cauda epididymal sperm ultrastructure, along with minimal discernible abnormalities in the fine structural cytology of the testes, further suggest that the site of action of this compound is posttesticular and may be confined to the cauda epididymal sperm. However, we cannot rule out an effect of triptolide that occurs during germ cell maturation but is delayed in its manifestation or triggered at the rete testis and epididymal level.
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PMID:Posttesticular antifertility action of triptolide in the male rat: evidence for severe impairment of cauda epididymal sperm ultrastructure. 1081 51

We investigated 115 testicular and 3 epididymal tumors and 6 cases of the complete androgen insensitivity syndrome (AIS) for the expression of inhibin-alpha, CD99, HEA125, PLAP, and chromogranin, using monoclonal antibodies and standard immunhistochemical techniques. Ihibin-alpha was detected in the neoplastic cells in 27 of 27 primary Leydig cell tumors (LCTs), 1 of 1 metastatic LCT, 6 of 20 Sertoli cell tumors (SCTs), 4 of 5 juvenile granulosa cell tumors (GCTs), and 2 of 5 unclassified sex cord-stromal tumors (USCSTs). Except for 2 choriocarcinomas, the choriocarcinomatous component of 1 mixed germ cell tumor, and a small focus of inhibin-positive syncytiotrophoblast in 1 embryonal carcinoma, inhibin-a immunoreactivity was not present in the neoplastic cells of the 38 remaining testicular germ cell tumors; 11 B-cell and 1 T-cell lymphomas; 1 granulocytic sarcoma; and 1 rhabdomyosarcoma of the testis; 1 adenoma of the rete testis, and 3 adenomatoid tumors of the epididymis. Inhibin-alpha immunoreactivity was present in the Sertoli cells and Leydig cells in 5 testicular hamartomas and in 1 Sertoli cell adenoma in 6 cases of AIS; both Sertoli and Leydig cells were also positive in the extranodular testicular parenchyma present in 2 of these cases. CD99 was detected in 10 of 15 primary LCTs, 1 of 7 SCTs, 3 of 5 JGCTs, and in 1 of 5 USCSTs but was not found in any tumor outside the sex cord-stromal category. HEA125 immunostaining was not detected in sex cord-stromal tumors; however, 3 of 12 seminomas, 3 of 12 embryonal carcinomas, 6 of 8 yolk sac tumors, and 1 of 2 teratomas were HEA125 positive. PLAP was not detected in sex cord-stromal tumors except for 4 of 15 primary LCTs but was present in most germ cell tumors. Chromogranin immunostaining was present in the sex cord-like element in 1 of 5 USCSTs, 1 of 8 YSTs, 1 of 2 teratomas, and in 1 of 1 rete adenoma, and in normal adjacent rete testis. In conclusion, although inhibin-alpha and PLAP, and, to a somewhat lesser extent, CD99 and HEA125 immunostaining are helpful in the differential diagnosis of certain testicular neoplasms that are difficult to distinguish on morphologic grounds, chromogranin is far less helpful in this context.
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PMID:Inhibin-alpha CD99, HEA125, PLAP, and chromogranin immunoreactivity in testicular neoplasms and the androgen insensitivity syndrome. 1101 71

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


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