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PubMed1985

Intermediate filament proteins in human testis and testicular germ-cell tumors.

Normal testicular tissue and 76 testicular germ-cell tumors of various types were immunohistochemically evaluated for the expression of intermediate filament proteins of different types. In normal testes, the rete testis epithelium was positive to cytokeratin, and the Sertoli cells, stromal cells, and Leydig cells were positive for vimentin. Cytokeratin-positive cells were also found lining atrophic seminiferous tubules and were occasionally seen within nonatrophic seminiferous tubules. The classical seminomas showed vimentin positivity, but this was usually observed in a small number of tumor cells. In addition, nearly half the seminomas contained single cytokeratin-positive cells, some of which were multinucleated and appeared to represent syncytiotrophoblastic giant cells. The tumor cells in embryonal carcinomas, endodermal sinus tumors, and choriocarcinomas displayed cytokeratin positivity. In some embryonal carcinomas vimentin-positive tumor cells were also found, probably representing attempts at further differentiation of the tumor cells. In immature teratomas, both the immature and the mature epithelial structures showed cytokeratin positivity. The stromal components, including cartilage, contained vimentin, and the smooth-muscle elements, desmin. Neural tissue positive for neurofilaments and glial tissue positive for glial fibrillary acidic protein, were observed in 5 and 3 of 15 cases, respectively. It is considered that antibodies to intermediate filaments are suitable tools to characterize the differentiation patterns of testicular germ-cell tumors and have the potential to aid in the differential diagnosis especially between seminoma and embryonal carcinoma.

Antibodies, Monoclonal↗
PubMed1994

Burned-out tumour of the testis presenting as retroperitoneal choriocarcinoma.

A case of "burned-out" tumour of the testis in a 20-year-old man is reported. The tumour presented as widespread retroperitoneal metastases. Orchiectomy displayed a subalbugineal fibrous scar close to the rete testis. Diagnostic biopsy of the unresectable retroperitoneal tumour showed a choriocarcinoma. Although appropriate chemotherapy was promptly started, the patient died 7 months after the initial complaints.

Adult↗
PubMed2005

A rare diagnosis: testicular dysgenesis with carcinoma in situ detected in a patient with ultrasonic microlithiasis.

A rare case is presented where a dysgenetic testis with microinvasive carcinoma in situ (CIS, also known as intratubular germ cell neoplasm of unclassified type [IGCNU] and testicular intraepithelial neoplasia [TIN]) with microinvasion to rete testis and the interstitial tissue was found in a 32-year-old man presenting with mild scrotal pain and ultrasonic testicular microlithiasis. Knowledge of the association of ultrasound and CIS is important to diagnose patients at the stage prior to development of an overt germ cell tumor. The patient had three of four disorders considered symptoms of the testicular dysgenesis syndrome (TDS): a dysgenetic left testicle with CIS, a mild left-sided cryptorchidism (high positioned scrotal hypotrophic testis) and a slightly reduced semen quality. Therefore, it should be kept in mind that a patient with one TDS symptom may harbour the other, even CIS or testicular cancer. Accordingly, patients with one TDS symptom ought to be examined for the presence of the others, and if more that one is present, extra concern is warranted.

Adult↗
PubMed1998

Postsurgical changes in the testis: a diagnostic dilemma.

Postsurgical changes in the testicle following epididymal surgery may mimic neoplastic transformation on ultrasound evaluation. We report a case in which postoperative ultrasound findings following epididymectomy, which in retrospect were consistent with tubular ectasia of the rete testis, resulted in unnecessary testicular biopsy and orchiectomy.

Adult↗
PubMed1977

The blood-testis barrier and temperature damage to the testis of the rat.

The integrity of the blood-testis barrier was investigated during and after local heating of rat testes sufficient to produce a temporary cessation of spermatogenesis. The flow, ionic composition and protein content of rete testis fluid (RTF) collected from testes maintained at 33 or 41 degrees C were unaffected either at the time of treatment or up to 2 days later when the major cytological consequences of heating occurred. The normally low rate of transfer of albumin from blood to RTF was unaffected during and after heating. Transfer constants for radioactive K, Rb, Na and lysine consistently increased during heating although there were time-dependent differences between the patterns of response for each molecule. The normally rapid transfer of testosterone was unaffected by heating, but the entry rates of radioactivity into RTF after the infusion of more slowly diffusing steroids were enhanced at 41 degrees C. The clearest effects of heating were an approximate doubling in the uptake of oxygen and decrease in the net synthesis of protein by the testis. It is concluded that heating sufficient to damage spermatogenesis was not associated with dramatic alterations in the integrity of the blood-testis barrier but more with changes in testicular metabolism.

Animals↗
PubMedDate not supplied

Myoid gonadal stromal tumor with epithelial differentiation (? testicular myoepithelioma).

A 46-year-old man presented with a cytologically bland testicular tumor composed of spindle cells that showed both epitheliallike (ie, true desmosomes and tonofilamentlike structures) and myogenous differentiation (ie, thin filaments with focal densities and alpha-smooth muscle actin immunoreactivity). Tumor cells were immunoreactive for vimentin and S-100 protein but negative for cytokeratin and desmin. Peritubular myoid cells are present in the normal testis; contain subplasmalemmal micropinocytotic vesicles; show thin filaments with focal densities; and are reactive with desmin, vimentin, and alpha-smooth muscle actin. They have no desmosomes and lie outside the basement membrane of the seminiferous tubules; thus they are not true myoepithelial cells (a cell type not present in the testis). Paradoxically, the current tumor appeared to show bidirectional differentiation, mimicking both a peritubular myoid spindle cell and an epitheliallike cell (possibly similar to the granulosa cell or rete testis epithelial cell). Although the findings suggest myoepithelial differentiation, the cytogenesis of this tumor remains uncertain.

Actins↗
PubMed1991

[Fundamental and clinical studies on alpha 1-blocker therapy for idiopathic male infertility].

Clinical usefulness of the alpha 1-blocker and beta-stimulant combined therapy for idiopathic male infertility has already been reported by Yamamoto et al. But the same trial followed by us revealed only a slight effectiveness and substantial adverse effects due to beta-stimulation. The mechanism of the alpha 1-blocker and beta-stimulant combined therapy is not yet established. In order to investigate its mechanism, fundamental study of alpha 1-receptor assay in the specimens of testis and various parts of male accessory sex organs obtained at the time of operation was done in this study. In addition the usefulness of alpha 1-blocker therapy for idiopathic male infertility was also examined clinically. The tissues used in this study were obtained from patients with prostatic cancer (23 cases), benign prostatic hyperplasia (24 cases), bladder cancer (6 cases), chronic epididymitis (3 cases), azoospermia due to disorders of vas deferens (5 cases) and a vasectomized man. Tritium labeled bunazosin was used as the ligand. The crude membrane fraction was extracted from the sample, with or without phentolamine incubated for 20 min at 37 degrees C. Maximal binding sites (Bmax) and the dissociation constant (Kd) were obtained by Scatchard plot analysis. Twenty-two infertile men were treated by oral administration of alpha 1-blocker (bunazosin, 3 mg/day) for 24 weeks. The results were as follows: 1) Bmax in the testis, epididymis, vas deferens and prostate, expressed as fmol, per mg. protein, was 2.27 +/- 1.74, 16.62 +/- 6.19, 29.44 +/- 17.81, 27.77 +/- 12.0, respectively (mean +/- S.D.). 2) Bmax in the rete testis was relatively high among various parts of the testis and seminiferous tubules. 3) Overall effective rates of sperm density and the sperm motility were noted in 36% at 12 weeks and 60% at 24 weeks after the therapy. 4) There was no clinical effect in patients with azoospermia and a slight effectiveness in patients with elevated plasma gonadotropin levels. 5) Adverse effect was reduced to 9.1%. These results suggest that the alpha 1-blocker therapy for idiopathic male infertility is clinically useful and that the mechanism of the therapy is through the action on male accessory sex organs behind the testis.

Administration, Oral↗
PubMed2005

[Influence of estradiol benzoate on the testis development of rats].

OBJECTIVE: To study the influence of estradiol benzoate (E2B) on the testis development of Sprague-Dawley (SD) rats. METHODS: Newborn male SD rats were injected subcutaneously with E2B (0.2 mg/5 g body weight). At days 14, 21, 28, 42 and 56 after birth, the rats were sacrificed after anaesthesia, and their testes were taken out and weighed. The cranial and caudal SEH and TD were measured respectively, the TD/SEH ratio in each part of the testis and the caudal SEH/cranial SEH ratio were calculated, and different stages of spermatogenesis were analysed. RESULTS: In the experimental group, the testis weight was significantly lower than that of the control (P < 0.01), the testes constantly remained in the abdominal cavity, and there was much fluid retention in the rete testis all the time. From day 21 on, the TD/SEH ratio in the cranial testis was much higher than in the control (P < 0.01), and so was the caudal SEH/cranial SEH ratio (P < 0.01). And spermatogenesis was obviously retarded as compared with the control (P < 0.01). CONCLUSION: Exposure of newborn male SD rats to E2B can cause fluid retention in the testis and cryptorchid, which in turn may retard spermatogenesis.

Animals↗
PubMed1976

The restricted penetration of iodinated rat FSH and LH into the seminiferous tubules of the rat testis.

The penetration of 125I-iodinated rat follicle-stimulating hormone (FSH; labelled by three different techniques) and luteinizing hormone (LH) through the walls of the seminiferous tubules of the rat testis has been studied by injecting the labelled hormone into rats with the efferent ducts of one testis ligated 16 h before the collection of samples of blood and tissues. The concentration of trichloracetic acid-precipitable and immunoprecipitable radioactivity was measured in blood plasma and rete testis fluid and calculated for the total secreted fluid retained in the testis by the ligature, and for the additional tubular fluid from the ligated testis, separated by centrifugation after decapsulating the testis and dispersing the cells. Very little intact hormone penetrated into the testicular fluids, even 16 h after injection of the labelled hormone, and the volume of distribution in the unligated testis of the trichloracetic acid-precipitable radioactivity was only slightly greater than that for markers known to be confined to the extracellular interstitial fluid. This suggests that the labelled hormones do not penetrate readily through the walls of the semiferous tubules into their lumina. Injected inorganic iodiide and trichloracetic acid-soluble 125I-circulating after the injection of iodinated hormones penetrated more rapidly into the tubules, but had not reached equilibrium between the testicular fluids and blood plasma 16 h after injection. Labelled FSH was reasonably stable in the circulation after injection, but 80% of the 125I was not protein-bound 16 h after injection of labelled LH.

Animals↗
PubMed2006

Estrogen response system in the reproductive tract of the male turtle: an immunocytochemical study.

Portions of the reproductive tract of the male (Trachemys scripta) turtle were examined by immunocytochemistry for evidence of the capacity to produce and respond to estrogen hormones (via the expression of P450 aromatase and estrogen receptors). Aromatase was detected in both the Sertoli and Leydig cells of the testis and was expressed at different levels during the spermatogenic cycle, being highest in the quiescent testis and lowest during germ cell meiosis. ERalpha was found in the Leydig cells surrounding the seminiferous tubules as well as in the epithelial cells of the excurrent canals (rete testis, efferent ductule, and epididymis). ERbeta immunoreactivity was found in both the spermatogonia and Sertoli cells in the testis, and in the epithelial cells of excurrent canals.

Animals↗
PubMed1988

Lesions of testis and epididymis associated with prenatal diethylstilbestrol exposure.

Cryptorchidism and retention of Müllerian duct structures occur with high frequency among the male offspring of CD-1 mice treated with 100 micrograms diethylstilbestrol/kg body weight on days 9 through 16 of pregnancy. Hyperplasia of the rete testis and Müllerian duct structures were found in many of the DES-treated male mice, as was a low but significant number of reproductive tract neoplasms.

Animals↗
PubMed1998

Reduction in fluid secretion by rat testis by drugs that block potassium channels.

The effect of two class III antiarrhythmic drugs (Almokalant, Astra-Hässle and Dofetilide, Pfizer) on fluid secretion by rat testes has been examined. Both drugs reduced fluid secretion, whether this was measured by the amount of rete testis fluid that could be collected 22 h after unilateral efferent duct ligation, or by the difference in mass between the ligated and unligated testes, or by the difference in amount of supernatant fluid after the parenchyma of the ligated and unligated testes had been dispersed and centrifuged. The secretion of potassium, calculated from the amount of potassium in the supernatant fluids from the ligated and unligated testes was also reduced by the drugs, whereas the secretion of androgen-binding protein and inositol was unaffected. The concentration of potassium in the secreted fluid, calculated from the amount and composition of the supernatant fluids, was not affected by treatment of the rats with Almokalant, but was increased in rats treated with Dofetilide and, in these, the concentration of sodium was reduced and that of magnesium and inositol was increased and the concentration of total protein was unaffected. The concentration of androgen-binding protein in secreted fluid was increased in rats treated with Almokalant, while the concentration of testosterone was unaffected. Histological examination of testes from treated rats revealed phagocytosis of stage 19 spermatids in tubules at stages VIII-IX after 2 days, at stages IX-XI after 4 days and at stages VIII-XIV after 7 days, apparently owing to an effect on spermiation. It appears that these drugs interfere with potassium-mediated fluid secretion by the testis, leading to the other changes seen.

Analysis of Variance↗
PubMed1992

Production of the cysteine proteinase inhibitor cystatin C by rat Sertoli cells.

The Sertoli cells of the rat testis produce cystatin C, a cysteine proteinase inhibitor. Primary culture of Sertoli cells secreted both unglycosylated and glycosylated forms of rat cystatin C. Despite the low concentration of cystatin C in rete testis fluid, equilibrium dissociation constants (Ki) for the interaction between cystatin C and lysosomal cathepsins indicate that this molecule could be involved in the local regulation of testicular cysteine proteinase activity which may be necessary for spermatogenesis and spermiogenesis.

Amino Acid Sequence↗
PubMed1991

Alpha 2-macroglobulin is not an acute-phase protein in the rat testis.

Earlier studies from this laboratory have shown that Sertoli cells actively synthesize and secrete a nonspecific protease inhibitor in vitro; N-terminal sequence analysis, subunit structural analysis, and other biological studies revealed that this protein is the homolog of serum alpha 2-macroglobulin. We have now quantified the relative distribution of alpha 2-macroglobulin in the reproductive compartments and their comparison with nonreproductive organs. In serum and all nonreproductive tissues examined, the concentration of alpha 2-macroglobulin progressively decreased with advancing age. However, in both the testis and epididymis, the levels of this protein increased with the age of the animals. Serum alpha 2-macroglobulin levels were consistently higher than those in any other tissues until 60 days when the concentrations of this protein were the highest in the epididymis. The distribution of alpha 2-macroglobulin in various nonreproductive tissues from female rats was similar to that observed for male rats in that its levels tended to decrease with age. However, uterine levels of alpha 2-macroglobulin increased progressively with advancing age, whereas ovarian levels of alpha 2-macroglobulin remained relatively stable with an increase in animal age. As serum alpha 2-macroglobulin is an acute-phase protein in the rat, the response of this protein in the testis to induced inflammation was examined. The concentration of alpha 2-macroglobulin in serum rose about 150-fold after injection of fermented yeast. By contrast, the levels of this protein in rete testis fluid, which is derived exclusively from seminiferous fluid, did not change in response to inflammation. These results suggest that there might be distinctive mechanisms that regulate this protein in the systemic circulation vs. the microenvironment behind the blood-testis barrier in the seminiferous epithelium.

Acute-Phase Proteins↗
PubMed1982

The effect of alkylating agents on the reproductive and hormonal testicular function in patients with rheumatoid arthritis.

An evaluation of testicular function was undertaken in 11 boys and young men aged 14-26 years suffering from rheumatoid arthritis complicated by amyloidosis and treated with cyclophosphamide and chlorambucil. 7 cases were studied during life and 4 at autopsy. Semen analysis showed azoospermia in 4 cases; in one, cryptozoospermia; in one, oligoasthenotheratozoospermia; and in one, asthenoteratozoospermia. In 4 patients with azoospermia and in one with cryptozoospermia, testicular biopsy was done for histo-pathological examination. In patients with azoospermia, only Sertoli cells were present in the seminiferous tubules. In one patient with cryptozoospermia, normal spermato- and spermiogenesis was found only in occasional seminiferous tubules. Microscopic examination of the testis failed to show any changes in the structure of the interstitial gland in any of the patients. Amyloid deposits were found in the vascular walls of the interstitial gland in one patient only. The serum testosterone level was depressed in 3 patients of the 9 examined. The LH level was elevated in 2 patients. The mean value of testosterone-LH ratio was significantly lower in patients treated with alkylating agents as compared with patients not so treated. Serum FSH level was elevated in 6 patients. Post-mortem examination of the testis in 4 patients showed complete absence of the germinal epithelium and only the presence of Sertoli cells. In 2 cases, amyloid deposits were found in the vascular walls in the rete testis. It was concluded that alkylating agents, besides damaging the testicular germinal epithelium, also affect the function of Leydig cells.

Adolescent↗
PubMed2003

Germ cell transplantation in an azoospermic Klinefelter bull.

Germ cell transplantation is a technique that transfers donor testicular cells into recipient testes. A population of germ cells can colonize the recipient testis, initiate spermatogenesis, and produce sperm capable of fertilization. In the present study, a nonmosaic Klinefelter bull was used as a germ cell recipient. The donor cell suspension was introduced into the rete testis using ultrasound-guided puncture. A pulsatile administration of GnRH was performed to stimulate spermatogenesis. The molecular approach to detect donor cells was done by a quantitative polymerase chain reaction with allele discrimination based on a genetic mutation between donor and recipient. Therefore, a known genetic mutation, associated with coat-color phenotype, was used to calculate the ratio of donor to recipient cells in the biopsy specimens and ejaculates for 10 mo. After slaughtering, meiotic preparations were performed. The injected germ cells did not undergo spermatogenesis. Six months after germ cell transplantation, the donor cells were rejected, which indicates that the donor cells could not incorporate in the testis. The hormone stimulation showed that the testosterone-producing Leydig cells were functionally intact. Despite subfertility therapy, neither the recipient nor the donor cells underwent spermatogenesis. Therefore, nonmosaic Klinefelter bulls are not suitable as germ cell recipients. Future germ cell recipients in cattle could be mosaic Klinefelters, interspecies hybrids, bulls with Sertoli cell-only syndrome, or bulls with disrupted germ cell migration caused by RNA interference.

Animals↗
PubMed2002

Expression of a blood-brain barrier-specific antigen in the reproductive tract of the male rat.

The endothelial barrier antigen (EBA) is a protein expressed specifically by the endothelial cells of the rat brain barrier vessels. This antigen has been described as a 'barrier protein' and is used as a marker for the competent blood-brain barrier. A blood-testis barrier has also been described. However, unlike the blood-brain barrier, which is formed by endothelial cells, the blood-testis barrier is formed mainly by the Sertoli cells, which provide an isolated environment for spermatogenic cells within the seminiferous tubules. Testicular blood vessels express the erythroid glucose transporter protein and other markers, which are strongly expressed in brain blood vessels, and may contribute to the blood-testis barrier. This study was carried out to determine whether Sertoli cells or testicular blood vessels express EBA. Tissues of other organs were used as controls for EBA expression. EBA was expressed by the endothelial cells in most microvessels of the testis, and in a few vessels of the epididymis, seminal vesicle, prostate gland, vas deferens and bladder-neck region. Furthermore, EBA was strongly and consistently detected in epithelial cells of the rete testis and dorsolateral prostate gland, and in a few epithelial cells of the ventral prostate gland, the seminal vesicle and the coagulating gland. However, Sertoli cells, which are the main site of the blood-testis barrier, were negative for EBA. In conclusion, EBA may have a wider role in rat tissues than has been previously appreciated.

Animals↗
PubMed2003

Dax1 regulates testis cord organization during gonadal differentiation.

Mutations of the DAX1 nuclear receptor gene cause adrenal hypoplasia congenita, an X-linked disorder characterized by adrenal insufficiency and hypogonadotropic hypogonadism. Targeted deletion of Dax1 in mice also reveals primary testicular dysgenesis, which is manifest by obstruction of the rete testis by Sertoli cells and hyperplastic Leydig cells, leading to seminiferous tubule dilation and degeneration of germ cells. Because Dax1 is expressed early in gonadal development, and because Sertoli and Leydig cells are located ectopically in the adult, we hypothesized that these testis abnormalities are the result of an early defect in testis development. In Dax1(-/Y) males, the gonad develops normally until 12.5 dpc. However, by 13.5 dpc, the testis cords are disorganized and incompletely formed in Dax1-deficient mice. The number of germ and Sertoli cells is unchanged, and the expression of Sertoli-specific markers appears to be normal. However, the number of peritubular myoid cells, which normally surround the testis cords, is reduced. BrdU labeling of peritubular myoid cells is low, consistent with decreased proliferation. The basal lamina produced by peritubular myoid and Sertoli cells is disrupted, leading to open and incompletely formed testis cords. Leydig cells, which normally reside in the peritubular space and extend from the coelomic surface to the dorsal surface of the gonad, are restricted to the coelomic surface of Dax1-deficient testis. We conclude that Dax1 plays a crucial role in testis differentiation by regulating the development of peritubular myoid cells and the formation of intact testis cords. The developmental abnormalities in the Dax1-deficient testis lay the foundation for gonadal dysgenesis and infertility in adult mice and, potentially in humans with DAX1 mutations.

Animals↗