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PubMed2005

Disruption of Sertoli-germ cell adhesion function in the seminiferous epithelium of the rat testis can be limited to adherens junctions without affecting the blood-testis barrier integrity: an in vivo study using an androgen suppression model.

During spermatogenesis, both adherens junctions (AJ) (such as ectoplasmic specialization (ES), a testis-specific AJ type at the Sertoli cell-spermatid interface (apical ES) or Sertoli-Sertoli cell interface (basal ES) in the apical compartment and BTB, respectively) and tight junctions (TJ) undergo extensive restructuring to permit germ cells to move across the blood-testis barrier (BTB) as well as the seminiferous epithelium from the basal compartment to the luminal edge to permit fully developed spermatids (spermatozoa) to be sloughed at spermiation. However, the integrity of the BTB cannot be compromised throughout spermatogenesis so that postmeiotic germ cell-specific antigens can be sequestered from the systemic circulation at all times. We thus hypothesize that AJ disruption in the seminiferous epithelium unlike other epithelia, can occur without compromising the BTB-barrier, even though these junctions, namely TJ and basal ES, co-exist side-by-side in the BTB. Using an intratesticular androgen suppression-induced germ cell loss model, we have shown that the disruption of AJs indeed was limited to the Sertoli-germ cell interface without perturbing the BTB. The testis apparently is using a unique physiological mechanism to induce the production of both TJ- and AJ-integral membrane proteins and their associated adaptors to maintain BTB integrity yet permitting a transient loss of cell adhesion function by dissociating N-cadherin from beta-catenin at the apical and basal ES. The enhanced production of TJ proteins, such as occludin and ZO-1, at the BTB site can supersede the transient loss of cadherin-catenin function at the basal ES. This thus allows germ cell depletion from the epithelium without compromising BTB integrity. It is plausible that the testis is using this novel mechanism to facilitate the movement of preleptotene and leptotene spermatocytes across the BTB at late stage VIII through early stage IX of the epithelial cycle in the rat while maintaining the BTB immunological barrier function.

Adherens Junctions↗

PubMed2000

A sds22 homolog that is associated with the testis-specific serine/threonine protein phosphatase 1gamma2 in rat testis.

Two cDNAs sequences (1320 bp and 1180 bp) of the 55-kDa subunit associated with a testis-specific serine/threonine protein phosphatase 1gamma2 (PP1gamma2) were cloned. They were the same up to 1180 bp, suggesting that they may be generated by alternative splicing. Sequence studies showed that the 1320 bp-cDNA is a homolog of the human sds22alpha(1) (thus, named rat sds22alpha(1)). The 1180 bp-cDNA is a new splice-variant since its sequence at the 3' end has not been identified in human sds22 genes (named rat sds22alpha(3)). The 1320 bp-cDNA is ubiquitously expressed in various tissues including the immature testis. However, the expression of 1180 bp-cDNA was only observed in the testis after puberty. This expression pattern matches very well with that of PP1gamma2, suggesting that 1180 bp-cDNA may encode the 55-kDa subunit to associate with PP1gamma2 in rat testis and is involved in spermatogenesis by controlling PP1gamma2 activity.

Aging↗

PubMed1992

Temporal correlation between the appearance of testis-specific DNA-binding proteins and the onset of transcription of the testis-specific histone H1t gene.

The histone H1t gene is transcribed only in testis. Northern blot analyses reveal that transcription of the H1t gene occurs first in pachytene primary spermatocytes. Thus, there is a temporal correlation between onset of transcription of the gene and synthesis of histone H1t in primary spermatocytes during spermatogenesis. Previous studies revealed that replacement of most H1t and core histones occurs during the midspermatid stage of spermiogenesis by transition proteins TP1 and TP2. In this paper we extend our study of the specific binding of testis nuclear proteins to a unique sequence element within the H1t promoter. The relatively tight binding is competed with an excess of homologous DNA but not with a mutated element. Testis proteins from prepubertal animals do not bind to the 18-bp promoter element out proteins from enriched populations of primary spermatocytes do bind. Therefore, the temporal correlation between onset of transcription of the H1t gene and the time when the specific H1t promoter-binding proteins are detected in primary spermatocytes suggests that the DNA-binding proteins might be germinal cell-specific transcription factors that participate in formation of an active H1t transcription initiation complex. These studies present the first analysis of binding sites for testis nuclear proteins from primary spermatocytes within the promoter of a gene expressed only during this stage of spermatogenesis.

Animals↗

PubMed1987

Nucleotide sequence of testis-derived c-abl cDNAs: implications for testis-specific transcription and abl oncogene activation.

The c-abl gene codes for a protein-tyrosine kinase and is expressed in most examined murine cell types as two distinct mRNA species of 5.5 kilobases (kb) and 6.5 kb. In mouse testis, an additional species of 4.0 kb is expressed in very high levels. To study the interrelationship between various c-abl transcripts and to compare their sequence with the v-abl transcript, we prepared c-abl-specific cDNA clones from mouse testis and determined the complete nucleotide sequence of the 4.0-kb cDNA that appears to be the reverse transcript of the testis-specific mRNA. In addition, we have determined the 3' sequence of an additional clone derived from the larger mRNA species that is expressed in somatic as well as germ-line cells. These cDNA sequences have been compared with the v-abl sequences to understand the mechanism of activation of this oncogene. The results demonstrate that (i) testis-specific c-abl mRNAs arise as a result of 3' truncation, and (ii) the v-abl gene has arisen from its cellular homologue as a result of an extensive deletional/mutational process.

Amino Acid Sequence↗

PubMed1998

Immunoexpression of testis-specific histone 2B in human spermatozoa and testis tissue.

During mammalian spermatogenesis, the chromatin of the spermatogenic cells is profoundly reorganized. Somatic histones are partly replaced by testis-specific histones. These histones are then replaced by transition proteins and finally by protamines. This series of nucleoprotein rearrangements results in a highly condensed sperm cell nucleus. In contrast to spermatozoa from other species, human spermatozoa still contain a significant amount of histones, including testis-specific histone 2B (TH2B). In the present study it is shown that an antibody targeting tyrosine hydroxylase, which has been found previously to cross-react with rat TH2B, also specifically immunoreacts with human TH2B on Western blots, in immunohistochemistry of human testis tissue, and in immunocytochemistry of decondensed human spermatozoa. In human testis tissue, TH2B immunostaining first apparent in spermatogonia, shows marked variation, especially at the pachytene spermatocyte stage, and then reaches an intense signal in round spermatids. Shortly before spermatid elongation, a portion of the spermatid nucleus, corresponding to the acrosomal region, loses its immunoreactivity. During condensation of the spermatid nucleus, the immunodetectability of TH2B disappears gradually, from the anterior region of the nucleus onwards. At the final stages of spermiogenesis, the immunostaining is completely absent. Immunocytochemical staining of spermatozoa revealed no TH2B immunosignal, but immunostaining was observed when spermatozoa obtained from semen were decondensed to make nuclear proteins accessible to the antibody. There was, however, a striking intercellular variability in the intensity of staining of spermatozoa within an ejaculate. In a population of 35 men attending our Andrology Clinic, we observed interindividual differences in total sperm TH2B content, which showed a significant, although not very pronounced, negative correlation with normal morphology (P = 0.05).

Animals↗

PubMed1998

Testis sparing surgery for infantile synchronous bilateral teratoma of the testis.

We report a rare case of infantile synchronous bilateral testicular teratoma treated by testis sparing surgery. Preoperative ultrasonography, tumor marker status and intraoperative findings were suggestive of benign neoplasia. Under these circumstances we performed high orchiectomy for the left testis and testis sparing surgery for the right. Surgical treatment of teratoma in childhood is controversial, especially when it occurs bilaterally. In this report we discuss testis sparing surgery as the treatment for this disease.

Biopsy↗

PubMed1969

A blood-testis barrier restricting passage from blood into rete testis fluid but not into lymph.

1. A permeability barrier in or around the seminiferous tubules of rams has been demonstrated by studying the rate of passage of a variety of substances from blood plasma into fluid collected from the rete testis and into testicular lymph.2. All substances studied passed readily into testicular lymph.3. Tritiated water, urea, ethanol and bicarbonate in rete testis fluid equilibrated with blood plasma within 3 hr; Na(+), K(+), Rb(+), Cl(-), I(-), CNS(-), creatinine and galactose entered slowly and p-aminohippurate (PAH), glutamate, iodinated albumin, inulin and [(51)Cr]EDTA did not appear in rete testis fluid at all.4. Rubidium was excluded relative to iodoantipyrine from the testes of control and hypophysectomized rats and from rat testes heated to 37, 40, 43 and 45 degrees C; no such exclusion was seen in testes of rats which had been given cadmium chloride 5 months earlier so as to destroy the seminiferous tubules.5. It is suggested that this permeability barrier will regulate the access to the seminiferous epithelium of some constituents of blood plasma, isolate the germinal cells immunologically and help to maintain the concentration differences between rete testis fluid and lymph or blood plasma.

Albumins↗

PubMed1998

DNA flow cytometry reveals depressed spermatogenetic activity in the contralateral testis within 24 h of ipsilateral spermatic cord torsion independently of the presence of the testis and epididymis.

An experimental study was planned to evaluate if contralateral testicular deterioration following ipsilateral torsion requires the presence of a twisted ipsilateral testis and/or epididymis. Five groups, each containing 6 rats, were established. The groups underwent sham operation, epididymo-orchiectomy, testicular torsion, torsion following subepididymal orchiectomy and torsion following epididymo-orchiectomy. After 24 h, the contralateral testes were harvested and the percentage of haploid cells was determined by DNA flow cytometry. Ipsilateral torsion, in the presence and absence of testis and epididymis, significantly decreased the number of haploid cells compared to sham and epididymo-orchiectomy procedures. Torsion of only the ipsilateral spermatic cord and adjacent vasculature seemed to suffice to damage the contralateral testis. Since the presence of the ipsilateral testis and epididymis is not mandatory for this acquired damage, which occurs within 24 h, a role for a preexisting congenital defect and autoimmunity seems unlikely.

Animals↗

PubMed1988

In vitro model of the first phase of testicular descent: identification of a low molecular weight factor from fetal testis involved in proliferation of gubernaculum testis cells and distinct from specified polypeptide growth factors and fetal gonadal hormones.

The gubernaculum testis is the connective tissue organ that causes the testis to descend. How the process of testicular descent is regulated is not fully understood. Current hypotheses postulate that a nonandrogenic fetal testicular factor controls the first phase of descent, that is characterized by growth of the gubernaculum and transabdominal migration of the testis. When gonadal extracts from fetuses with ages corresponding to the first phase of testicular descent (50, 60, and 75 days) were tested on gubernacular cells, the growth stimulatory effect of testicular extracts exceeded the effect of both ovarian extract and fetal calf serum. Gonadal extracts from 80-, 90-, and 100-day-old fetuses showed only a minor sex difference. No sex difference or age-dependent changes were detected when fetal gonadal extracts were tested on murine 3T3 cells. Polypeptide growth factors (epidermal growth factor, insulin, fibroblast growth factor, platelet-derived growth factor, and transforming growth factor-beta) were tested for growth stimulatory activity and had only minor effects on gubernaculum cells. Fetal testicular hormones (anti-Müllerian hormone, inhibin, and androgenic steroids) did not induce initiation of DNA synthesis at concentrations that are highly bioactive in typical target systems. When testicular samples were dialyzed, the high mol wt fraction (greater than 3500) had lower growth stimulatory activity in gubernaculum cells, but not 3T3 cells. Bioactivity of ovarian extracts and fetal calf serum was not diminished after dialysis. The low mol wt fraction (less than 3500) of testicular extract was distinctly stimulatory to gubernaculum cells but not 3T3 cells, and the low mol wt fraction of ovarian extracts did not stimulate growth in either cell type. It was concluded that the fetal porcine testis during the first phase of testicular descent contains low mol wt factor(s) to which gubernaculum cells and not 3T3 cells are responsive. The bioactive fraction probably contains the factor(s) that initiate testicular descent. We suggest the name descendin for this new activity.

Androgens↗

PubMed2003

[Molecular cloning and expression in cryptorchid testis of SRG2 from a mouse testis spermatocyte apoptosis-related gene].

It was observed that the spermatogenic cells apoptosis dramatically increased in infertile man. Cloning of novel spermatogenic cell-specific gene related to apoptosis is of momentous physiological and pathological significance to illustrate the apoptosis mechanism and the biology process of spermatogenic cells. A novel mouse gene full-length cDNA sequence-SRG2 was identified (GenBank accession number AF395083), which was significantly changed in cryptorchidism, from a mouse testis cDNA library using a cDNA fragment (GenBank accession number BE644542) as an electronic probe. SRG2 was 1,088 bp in length. The putative protein encoded by this gene was 295 amino acids with a theoretical molecular weight of 33,579 kDa and isoelectric point of 9.64. The sequence shared no significant homology with any known protein in databases except TSARG2, with which its homology was 78%. RT-PCR showed that SRG2 was expressed significantly in testis. Using molecular beacon probe to examine the mRNA expression level of SRG2 gene in cryptorchid testis of various stages, we found that the gene was up-regulated distinctly. Therefore, we conclude that this gene plays an important role in cryptorchid testis.

Amino Acid Sequence↗

PubMed1984

[Microsomal glucose 6-phosphate dehydrogenase in the rat testis--an testis--specific isoenzyme?].

Mammalian tissues contain cytosolic and microsomal glucose 6-phosphate dehydrogenase (G6PD). In the present study it was examined whether the microsomal G6PD in liver and testis of the rat are homologous. Kinetic parameters and immunological reactivity were estimated using rabbit antiserum against mice erythrocyte G6PD. Kinetic parameters allow to distinguish cytosolic and microsomal G6PD in rat liver but not in testis, whereas the immunological properties of the testis enzymes are different. The cytosolic G6PDs from liver and testis of the rat are identical enzymes having extremely similar properties to mice erythrocyte G6PD. The microsomal G6PD of both organs are not homologous enzymes. Testicular microsomal G6PD is likely to be an organ specific G6PD-isoenzyme.

Animals↗

PubMed2002

Cystic dysplasia of the testis: a very rare paediatric tumor of the testis.

OBJECTIVES: To describe a case of cystic dysplasia of the testis (CDT), an uncommon cause of scrotal swelling in the pediatric patient. Clinic, therapy, fertility, and radiographic and pathologic findings are discussed and the 30 previously reported cases are reviewed. METHODS: A 9-year-old boy presented with asymptomatic scrotal swelling. A scrotal ultrasound showed a multicystic scrotal mass in the rete testis and an ipsilateral renal agenesis. The growth in size of the mass forced the authors to perform an operative exploration. RESULTS: Intraoperative findings included a multicystic mass in the rete testis of the right testicle. Testicle-sparing total removal of the multicystic mass was performed and the pathologic examination revealed a benign, multilobulated configuration of the cysts in the region of the rete testis. These findings were similar to those found in previously reported cases of CDT. Ipsilateral renal agenesis is the most common associated anomaly. As a pathogenetic factor, mal-junction of the Wolffian duct in the 5th week of gestation is most creditable. CONCLUSIONS: CDT is a rare cause of pediatric scrotal mass. When feasible, a testicle-sparing approach should be considered and all patients should undergo evaluation for associated urologic anomalies.

Child↗

PubMed1991

A national programme for testis cancer, the Irish Testis Tumor Registry (ITTR).

The fundamental aims of the ITTR are to perform research into testis cancer and maximize nationwide disease control. Authors compare regional trends: Ireland, England and Wales. In Ireland, between 1961 and 1984 in the 25 to 34 years age group, the mortality rate increased 123%. In contrast, in England and Wales, the number of deaths has decreased by 17%. The highest mortality rates of all, occurred in those Irish aged over 75 years old. The Irish incidence of testis cancer is 2.4 per 100,000 males per year. Seven countries have lower levels than Ireland, while ten countries have higher levels. Incidence was highest in young adults (5.8 per 100,000) with a moderate level seen in the elderly (1.8 per 100,000). Cases of testis cancer, in Ireland, were grouped as seminomas (45%, n = 101) or non seminomas (55%, n = 131). In seminomas, overall three year actuarial survival was 80%, stage I = 94%, stage II = 72% and stages III and IV = 23%. A variety of treatments were utilized and the results are presented. In non-seminomas, overall three year actuarial survival was 65%, with stage I = 95%, stage II = 54% and stages III and IV = 24%; a variety of treatments were used. A further study was designed ot establish whether personnel and the manner of management can influence the outcome in testis cancer. Survival in patients not receiving full dose cytotoxics was significantly lower than those receiving standard doses. Survival was reduced from 72% to 64% when marker assays were omitted and infrequent monitoring with CT scan was associated with reduced survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Health Knowledge, Attitudes, Practice↗

PubMedDate not supplied

[Scanning electron and light microscopic studies of the surface epithelium of the rete testis and epididymis of the boar. I. Rete testis and efferent ducts].

The use of the scanning electron microscope gave a three dimensional representation of the epithelial surface. Additionally, light microscopy revealed the representative structure of the epithelium. The rete testis showed a single layer of cubic epithelial cells. Short and dense microvilli were found on the surface. Sporadically a single, cilia-like structure was recognized. An extratesticular rete testis was identified. The flowing transition of the epithelium between the rete testis and the efferent ductuli occurred at different levels, so that both kinds of epithelial structures were recognized in the same area. The efferent ductuli were composed of a single columnar epithelium consisting of two cell types, principal cells and ciliated cells. The ciliated cells were recognized by their cilia protruding into the lumen. The principal cells showed microvilli on their surface and bleblike apical protrusions which erupt into the lumen.

Animals↗

PubMed1990

Adenomatous hyperplasia of the rete testis in the undescended testis.

Multiple foci of micronodular or tubulopapillary structures were noted in the rete testis of 13 cases of undescended testes. These structures were lined by low columnar to cuboidal epithelium, showed back-to-back crowding, and were supported by a thin lamina propria. These changes, referred to as adenomatous hyperplasia of the rete testis, appear to be a frequent finding in the undescended testis. An age-matched control group did not show any of these features.

Adolescent↗

PubMed1979

The role of the epididymis in descensus testis and the topographical relationship between the testis and epididymis from the sixth month of pregnancy until immediately after birth.

The position of the testis, the relationship between the epididymis and the testis, as well as the development and regression of the gubernaculum were investigated in 18 testicles of children from the 26th week of pregnancy until a few weeks after birth. The most important role in descensus testiculorum is ascribed to the differentiation of the epididymis and the ductus deferens. It is androgen dependent. The testis descends in the processus vaginalis, being attached to its dorsal wall.

Epididymis↗

PubMed2003

Revascularization of the testis using a vascular induction technique: a potential approach for staged orchiopexy in high-undescended testis.

The present study was designed to determine whether a fasciovascular flap as a vascular carrier could be used to revascularize the undescended testis for avoiding the hazardous effects of the Fowler-Stephens procedure, high division of the spermatic vessels, and for bringing high-undescended testes into the scrotum. A total of 25 Wistar rats were divided into five groups of five rats each. In each group, surgical procedures were performed bilaterally, i.e. ten testes in each group, as follows: sham-operated controls (group 1), undescended testes (group 2), high division of the spermatic vessels (group 3), vascular induction with immediate division of spermatic vessels (group 4), and with delayed division of spermatic vessels (group 5). Evaluations were done by measuring the testicular weight and volume, testicular blood flow, and testicular biopsy scores and by microangiography. A moderate to severe decrease in testicular weight and volume in all experimental groups was observed compared with the sham-operated controls (group 1), but this was significantly less in groups 2 and 5. High division of the spermatic vessels in groups 3 and 4 resulted in a significantly greater decrease in the testicular blood flow, but this did not occur in group 5. Microangiographically, an impaired vascular supply from the deferential artery in group 3 and insufficient revascularization from the fasciovascular carrier in group 4 were observed. However, efficient revascularization stemming from the superficial epigastric artery of the fasciovascular flap was found in group 5. The testicular biopsy scores of groups 2 and 5 were significantly greater than those of groups 3 and 4. The results of the present study demonstrate that the fasciovascular flap as a vascular carrier revascularizes the testis through spermatic vessels after delayed division and provides an adjuvant treatment modality or first-stage procedure in a salvage operation for high-undescended testis during staged orchiopexy.

Angiography↗

PubMed1993

Circular transcripts of the testis-determining gene Sry in adult mouse testis.

Sry is expressed at higher levels in the adult testis, where no function has been determined, than in the genital ridge, its critical site of action. cDNA and 5' RACE clones isolated from testis or from Sry-transfected cell lines have an unusual structure, with 3' sequences located in a 5' position. RNAase protection assays and reverse transcription polymerase chain reactions confirmed that these unusual RNA molecules represent the most abundant transcript in testis. Furthermore, oligonucleotide hybridization and RNAase H digestion proved that these Sry RNA molecules are circular. Similar transcripts were detected in the testes of mice with Mus musculus musculus, Mus musculus domesticus, and Mus spretus Sry genes. The circular RNA is found in the cytoplasm but is not substantially bound to polysomes. We suggest that the circles arise from normal splicing processes as a consequence of the unusual genomic structure surrounding the Sry locus in the mouse.

Animals↗