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PubMed1985

[A case of cavernous hemangioma of the testis].

Non-germinal cell tumor of the testis is a rare disease, and vascular tumor of the testis is a still rarer disease. Herein, a case of cavernous hemangioma of the testis is reported. A 75-year-old man consulted our department with the complaint of a painless left intrascrotal tumor. Laboratory findings revealed slight leukocytopenia and thrombocytopenia of unknown origin. In chest X-ray, a diffuse reticular shadow was shown and it was considered due to pulmonary fibrosis, but, alpha-fetoprotein and CEA were normal. Left radical orchiectomy was performed under spinal anesthesia. The tumor existed under the tunica albuginea, and the cutting surface of the tumor was brown and irregular. There were hemorrhagic portions in some places. The left epididymis and the left spermatic cord were normal. Histologically, the tumor was diagnosed as cavernous hemangioma. The vascular tumor of the testis is a very rare disease, and only 17 cases have been reported including this case. This case was the 7th case of cavernous hemangioma of the testis, and the first case in Japan. This patient died of respiratory failure due to pulmonary fibrosis and pneumonia. In the autopsy, there was no abnormal finding that was considered to be related to the cavernous hemangioma of the testis.

Aged↗

PubMed1995

[Epidermoid cyst of testis: benign testicular tumor].

Epidermoid cyst of the testis is very rare and accounts for approximately 1% of all testicular tumors. In the clinical examination, the testis has a palpable mass. Pathological findings usually reveal a squamous cell lined cyst, containing keratin, and the absence of appendages and teratoma element. If scrotum ultrasonography reveals a target sign suggestive of epidermoid cyst, the testis should be explored through an inguinal incision. Clamp the spermatic cord gently, and perform tumor enucleation. The frozen section is available at the time to check for any malignant cells. If no malignant cells exist, it is important to perform testis-preserving surgery, especially for young adults and children. We report two cases of epidermoid cyst. Serum beta-HCG and alpha-fetoprotein were within normal limits. We review our experience with scrotum ultrasonography and testis-preserving surgery in 2 men with epidermoid cyst to indicate when the clinical and intraoperative characteristics justify testis-preserving management.

Adolescent↗

PubMed1993

Mutations of the p53 gene do not occur in testis cancer.

To characterize the role of p53 in the development of testis cancer, we looked for mutations in the coding sequences of the p53 gene. DNA was obtained both from familial and sporadic testis cancer specimens, as well as from peripheral blood from members of a testis cancer kindred. Mutations in the p53 gene were screened using a combination of constant denaturant gel electrophoresis and single-strand conformational polymorphism analysis, 2 screening methods that can detect single base changes. Abnormalities detected by these methods were confirmed by sequencing of the corresponding cloned polymerase chain reaction products. All conserved regions of the p53 coding sequences were examined, encompassing all previously reported sites of mutations. No mutations were found in any of 22 germ cell cancers of the testis or in the germline DNA of 17 members of the testis cancer family. This is in striking contrast to most other human cancers, in which mutations of p53 are the most commonly described molecular event associated with tumorigenesis. We conclude that dysfunction of tumor suppressor gene or genes other than p53 may prove to play an important role in the development of germ cell cancers of the testis.

Genes, p53↗

PubMed1997

Primary mediastinal germ cell tumor with intratubular germ cell neoplasia of the testis--further support for germ cell origin of these tumors: a case report.

BACKGROUND: The histogenesis of extragonadal germ cell tumors remains an enigma. The majority of patients with retroperitoneal tumors are male, and careful histologic evaluation reveals preinvasive intratubular germ cell neoplasia (ITGCN) or scars in the testis suggesting a so-called "burnt out" germ cell tumor. However, in the testes of patients with primary mediastinal germ cell tumors, no ITGCN has been described in the literature to date. The authors report the first case of simultaneous germ cell neoplasia in the mediastinum and the testis, providing further insights into the biology and origin of these lesions. METHODS: The authors report the pathologic features and cytogenetic findings in an adult male with a mediastinal germ cell tumor and asymmetric testis. This patient died shortly after diagnosis. RESULTS: A locally invasive mediastinal nonseminomatous germ cell tumor was associated with ITGCN in one testis. Metastases were not present clinically or on autopsy during a detailed and systematic examination of retroperitoneal lymph nodes and other viscera. Neither an invasive germ cell tumor nor a scar was found in either testis (both testes were serially sectioned and entirely examined histologically). CONCLUSIONS: The findings of this study suggest that the mediastinal tumor is a primary neoplasm with concomitant in situ lesion in one testis, suggesting a more generalized defect of germ cell and thus providing new information about the unresolved issue of the histogenesis of extragonadal germ cell tumors. This article presents a review of the literature concerning the issues highlighted by this case and discusses the hypotheses regarding the development of extragonadal germ cell tumors.

Adult↗

PubMed1997

Is the ascending testis actually 'stationary'? Normal elongation of the spermatic cord is prevented by a fibrous remnant of the processus vaginalis

The processus vaginalis (PV) forms as a peritoneal diverticulum within the gubernaculum testis to allow the testis to exit from the abdominal cavity. Failure of its closure leads to inguinal hernias and hydroceles. Ascending testis, which is likely to be an acquired form of undescended testis, may also be part of the spectrum of failure of regression of the PV. At orchidopexy for cryptorchidism in older boys with a history of a scrotal testis in infancy, we find that the PV persists as a fibrous string, preventing normal elongation of the vas deferens and gonadal vessels with increasing size of the boy. We propose that the ascending testis is actually 'stationary', and is caused by persistence of a fibrous remnant of the PV. Seen in this light, ascending testes are directly related to inguinal hernias.

Journal Article↗

PubMed1997

Testis sparing surgery for steroid unresponsive testicular tumors of the adrenogenital syndrome.

PURPOSE: Surgical management of steroid unresponsive testicular tumors of the adrenogenital syndrome has been orchiectomy. Magnetic resonance imaging (MRI) of these tumors accurately delineates the extent of disease. Testis sparing surgery is an important consideration, since male individuals with congenital adrenal hyperplasia are potentially fertile. We present our results of surgical management of this tumor based on MRI findings. MATERIALS AND METHODS: Four boys with steroid unresponsive testicular tumors of the adrenogenital syndrome were evaluated with MRI, testicular ultrasound and color flow Doppler examinations preoperatively and postoperatively. Three patients had 21-hydroxylase deficiency and 1 had 3-beta-hydroxysteroid dehydrogenase deficiency. Contralateral testicular abnormalities included a vanished testis, testicular atrophy due to trauma and bilateral tumors in 1 boy each. Bilateral orchiectomy and surgical enucleation were performed in 1 and 3 patients, respectively. Followup ranged from 8 to 18 months. RESULTS: Postoperative MRI of the testis in 2 of 3 patients showed no evidence of recurrent tumor. Postoperative testicular sonography revealed no tumor and vascular flow in 2 of 3 patients. All 3 patients who underwent testis sparing surgery have a viable testis in the scrotum without evidence of recurrent disease. CONCLUSIONS: MRI of the testis in patients with testicular tumors of the adrenogenital syndrome accurately defines the extent of disease. Surgical enucleation of this tumor has been performed successfully without recurrent disease. This surgical approach should be considered for any patient with a steroid unresponsive tumor and contralateral abnormalities. We believe that surgical enucleation is the procedure of choice for all patients with this tumor, since it maximizes future fertility potential.

Adolescent↗

PubMed1997

Is the ascending testis actually 'stationary'? Normal elongation of the spermatic cord is prevented by a fibrous remnant of the processus vaginalis.

Calcitonin Gene-Related Peptide↗

PubMed1998

Torsion of a malignant undescended testis.

Cryptorchid testis have a greater risk of malignant change than do normally descended testis. The undescended testis would also be susceptible to torsion by the mechanism of increase in testicular size. A 36-year-old man of torsion of malignant undescended testis is presented. He was diagnosed as having incarcerated inguinal hernia on his first visit to general surgeon due to acute left lower abdominal pain. At laparotomy, a 7.5 x 5.5 x 3.0 cm3, greyish tan color mass was found. The pathological diagnosis is choricarcinoma and teratoma, mixed germ cell tumor. We would emphasise that in any patient presenting with acute abdominal symptoms and an absent scrotal testis, the possibility of a complication of torsion of undescended testis should be considered.

Adult↗

PubMed1994

Developmental expression of the glutathione S-transferase Yo subunit in the rat testis and epididymis using light microscope immunocytochemistry.

BACKGROUND: Glutathione S-transferases (GSTs) are a family of isozymes that catalyze the conjugation of glutathione with various toxic electrophilic compounds. GSTs are composed of several classes based on the degree of sequence homology of their subunits. The Yo subunit, a member of the mu class, is expressed at high levels in the testis and epididymis. The purpose of this study was to immunolocalize the GST-Yo in these tissues during development. METHODS: The testes and epididymides of rats aged 7, 15, 21, 28, 39, 42, 45, 49, and 56 days were fixed in Bouin's fixative, and immunostained for light microscopic analysis. RESULTS: In the testis the cytoplasm of all germ cells was unreactive until day 39. At that time, step 18 spermatids appeared moderately reactive, while the few observed step 19 spermatids were intensely reactive as were their residual bodies. The presence of residual bodies indicates that spermiation takes place as early as day 39; however, the number of step 19 spermatids is low at this age. A progressive increase in the size of the tubule and number of elongating spermatids was seen between days 42 and 49. In addition, by day 49, a weak staining was observed in steps 12-15, moderate in steps 16-17, and intense in steps 18-19 spermatids. In terms of the intensity of staining, cell types stained, size of the tubules, and number of elongating spermatids, no difference was noted between day 49, 56, and adult animals. Thus Yo protein expression in germ cells reached maturity by day 49. The epithelial cells of the rete testis were intensely reactive at day 7 and remained so throughout development. In contrast, while the epithelial cells of the efferent ducts at day 7 were intensely reactive, they were weakly reactive by day 39 and remained so at later ages. Along the entire epididymis, the columnar epithelial cells showed a moderate apical/supranuclear reaction from day 7 to 28. By day 39 principal cells of the initial segment became weakly reactive, while those in the caput and corpus were moderately stained, a situation seen at later ages including adults. Only by day 49 did principal cells of the proximal cauda become moderately stained as seen in adult animals. Thus the expression of the Yo protein in the principal cells of the proximal cauda may be regulated by different factors than those of the caput and corpus epididymidis. Alternatively, the expression of the Yo subunit in principal cells of the proximal cauda may develop later since this region would be the last to receive luminally derived testicular products. In the initial segment, the decrease in staining of principal cells at day 39 may be due to an inhibiting factor emanating from the testis. Spermatozoa appeared in the lumen of each epididymal region well after the expression of Yo had reached its adult staining pattern indicating that they are not a factor. CONCLUSIONS: Overall these results suggest that the expression of GST-Yo in the various cells of the testis and epididymis are controlled by different factors during postnatal development.

Animals↗

PubMed1976

The rete testis in man: ultrastructural aspects.

The ultrastructure of the normal human rete testis was analyzed. The rete testis cavities are irregularly shaped and contain virtually no spermatozoa. Smooth muscle cells often surround the cavities. In the epithelial lining, two cell types are distinguishable. Flat, dark cells exhibit numerous slender microvilli, and numerous apical and basal micro-vesicles. Prismatic, lighter cells have more cell organelles, mostly polarized towards a supranuclear position. Both cell types contain variable amounts of glycogen and fat, and an occasional cilium. All cells display intricate lateral cell surfaces that possess different cell-to-cell attachment devices. Intermediate cell types are frequently found. On a morphological basis, the epithelial cells seem to be involved in the release of substances into the lumen and probably also in transport towards the base. Connective tissue elements are found subjacent to the epithelium. Scattered among the fibrocytes are typical smooth muscle cells. Expansions of some smooth muscle cells are connected to the epithelial basement membrane by a network of microfibrillar materia. The smooth muscle cells may be involved in changing the shape of the rete testis channels, thus promoting the flux of the rete testis fluid. Different types of nerve fibre bundles are distinguished in the connective tissue of the rete testis which may correspond to autonomic and sensory nerves or sensory receptors.

Adult↗

PubMed2006

Stage-dependency of apoptosis and the blood-testis barrier in the dogfish shark (Squalus acanthias): cadmium-induced changes as assessed by vital fluorescence techniques.

Naturally occurring heavy metals and synthetic compounds are potentially harmful for testicular function but evidence linking heavy metal exposure to reduced semen parameters is inconclusive. Elucidation of the exact stage at which the toxicant interferes with spermatogenesis is difficult because the various germ cell stages may have different sensitivities to any given toxicant, germ cell development is influenced by supporting testicular somatic cells and the presence of inter-Sertoli cell tight junctions create a blood-testis barrier, sequestering meiotic and postmeiotic germ cells in a special microenvironment. Sharks such as Squalus acanthias provide a suitable model for studying aspects of vertebrate spermatogenosis because of their unique features: spermatogenesis takes place within spermatocysts and relies mainly on Sertoli cells for somatic cell support; spermatocysts are linearly arranged in a maturational order across the diameter of the elongated testis; spermatocysts containing germ cells at different stages of development are topographically separated, resulting in visible zonation in testicular cross sections. We have used the vital dye acridine orange and a novel fluorescence staining technique to study this model to determine (1) the efficacy of these methods in assays of apoptosis and blood-testis barrier function, (2) the sensitivity of the various spermatogonial generations in Squalus to cadmium (as an illustrative spermatotoxicant) and (3) the way that cadmium might affect more mature spermatogenic stages and other physiological processes in the testis. Our results show that cadmium targets early spermatogenic stages, where it specifically activates a cell death program in susceptible (mature) spermatogonial clones, and negatively affects blood-testis barrier function. Since other parameters are relatively unaffected by cadmium, the effects of this toxicant on apoptosis are presumably process-specific and not attributable to general toxicity.

Animals↗

PubMed1989

Nodular proliferation of calcifying connective tissue in the rete testis: a study of three cases.

We report the first description of a bilateral rete testis lesion. The lesion was found in three adult men with histories of myocardium infarct or hemorrhage. The histologic study of the rete testis in these men revealed nodular sessile or pediculate formations which protruded into the rete testis channels. These polypoid formations consisted of an axis of connective tissue covered by a flattened epithelium. The axis contained a variable number of fibroblasts, areas with fibrin-like material, and small to large calcium deposits. Inflammatory infiltrates were neither observed in the rete testis nor in the testicular parenchyma. The testicular pattern varied from seminiferous tubules with complete spermatogenesis (two cases) to tubules with Sertoli cells and a few spermatogonia, surrounded by a thickened tunica propia. The term "nodular proliferation of calcifying connective tissue in the rete testis" is proposed to designate this lesion.

Aged↗

PubMed2002

An oncological view on the blood-testis barrier.

The function of the blood-testis barrier is to protect germ cells from harmful influences; thus, it also impedes the delivery of chemotherapeutic drugs to the testis. The barrier has three components: first, a physicochemical barrier consisting of continuous capillaries, Sertoli cells in the tubular wall, connected together with narrow tight junctions, and a myoid-cell layer around the seminiferous tubule. Second, an efflux-pump barrier that contains P-glycoprotein in the luminal capillary endothelium and on the myoid-cell layer; and multidrug-resistance associated protein 1 located basolaterally on Sertoli cells. Third, an immunological barrier, consisting of Fas ligand on Sertoli cells. Inhibition of P-glycoprotein function offers the opportunity to increase the delivery of cytotoxic drugs to the testis. In the future, visualisation of function in the blood-testis barrier may also be helpful to identify groups of patients in whom testis conservation is safe or to select drugs that are less harmful to fertility.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1988

Structural analysis of clusterin and its subunits in ram rete testis fluid.

Clusterin is a protein present in the rete testis fluid of the ram that elicits aggregation of erythrocytes and Sertoli cells in vitro. In view of its possible biologic function in relation to cell-cell interaction in the testis, we isolated this protein from ram rete testis fluid using sequential high-performance liquid chromatography columns and performed a detailed physicochemical characterization. This protein consists of two molecular variants designated form I and form II clusterin. Each form of clusterin consists of two subunits with an apparent molecular weight of 40,000. It is of note that the two subunits have no homology in their N-terminal amino acid sequences. However, the N-terminal amino acid pairs of the two subunits derived for the two forms of clusterin are identical. Using o-phthalaldehyde to block the Lys residue at the fourth amino acid pair from the N-terminus which leaves the Pro residue free for subsequent Edman degradation, we have deduced the N-terminal sequence of each of the two subunits for form I clusterin. Comparison of the NH2-terminal sequences of the two subunits of clusterin with the release 10.0 of the protein sequence data base of the Protein Identification Resource indicated no homology between either of the subunits of clusterin and any of the known proteins in the data base. A highly specific radioimmunoassay developed for clusterin was used to measure its concentrations in the fluids of the rete testis and cauda epididymis. Since a significant amount of immunoreactive clusterin was found in serum, the protein was partially purified from this source by immunoaffinity chromatography. Immunoreactive serum clusterin was smaller than the testicular clusterin (Mr 37,000 vs 40,000), but both proteins share common epitopes as demonstrated by radioimmunoassay and immunoblots. However, serum clusterin does not possess the biologic activity of the testicular clusterin in that it does not elicit cell aggregation in vitro. It is of note that deglycosylation of testicular clusterin can also eliminate this in vitro biologic activity, suggesting that the serum clusterin might be a deglycosylated form of the testicular protein and the carbohydrate core plays an important role in determining the cell aggregation activity. Studies on the distribution of this protein in the reproductive compartment indicate that it is highly concentrated in the rete testis and the cauda epididymal fluids. This suggests that this protein might have some important functions in the reproductive tract.

Amino Acid Sequence↗

PubMed2002

Multidrug resistance genes and p-glycoprotein in the testis of the rat, mouse, Guinea pig, and human.

Study of the multidrug resistance phenomenon in tumor cell lines has led to the discovery of the product of the multidrug resistance (MDR) type 1 genes, the plasma membrane P-glycoprotein (P-gp) that functions as an energy-dependent pump for the efflux of diverse anticancer drugs. P-gp was also recently identified in normal epithelial cells with secretory/excretory functions and in the endothelial cells of the capillary blood vessels in the brain and the testis. These endothelial cells are key elements of the blood-brain and blood-testis barriers, respectively. The aim of this study, in the rat, mouse, guinea pig, and human, was to determine whether testicular cells other than the capillary endothelial cells could express MDR type I genes. Immunohistochemistry on testicular sections revealed that P-gp is present in interstitial cells in the mouse, rat, and human testes, in early and late spermatids in guinea pig testis, and in late spermatids in the rat, mouse, and human. Reverse transcription-polymerase chain reaction analysis on isolated mouse, rat, and human cells showed that all somatic testicular cells (Leydig cells, macrophages, peritubular cells, and Sertoli cells) and the cytoplasmic lobes from rat late spermatids expressed MDR type I mRNAs, whereas spermatogonia, pachytene spermatocytes, and early spermatids did not. An ontogenesis study in the mouse reveals that type I MDR gene expression begins at 13.5 days postcoitum at the time when the seminiferous cords and the blood vessels appear and are maintained thereafter. Finally, two functional tests on isolated rat cells, the doxorubicin and rhodamine uptake assays, demonstrated that rat testicular macrophages, Leydig cells, peritubular cells, and Sertoli cells displayed a multidrug-resistance activity, whereas spermatogonia, pachytene spermatocytes, and early spermatids did not. Western blot experiments have revealed that a P-gp of 175 kDa is present in the human testis as well as in the rat Leydig cells, testicular macrophages, peritubular cells, and Sertoli cells, but is absent in spermatogonia, spermatocytes, and early spermatids. We conclude that P-gp is involved in the self-protection of the somatic cells and is most probably one of the molecules that confers its functionality to the blood-testis barrier. The absence of expression of MDR type I genes in mitotic and meiotic germ cells probably explains their particular vulnerability to various anticancer drugs. In contrast, expression of the P-gp in the haploid cells most likely reflects the ability of spermatozoa to assume their own antidrug defense.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1987

Isolation and culture of ram rete testis epithelial cells: structural and biochemical characteristics.

Cultures of rete testis epithelial cell-enriched preparations from testes of adult rams have been investigated, and some of their properties have been determined. In monolayers, the cells form mosaic-like borders, and retain many ultrastructural features characteristic of rete epithelial cells in situ, including an indented nucleus with prominent heterochromatin clumps, short rod-shaped or round mitochondria that are easily distinguished from the elongated mitochondria of Sertoli cells, the presence of desmosomes, and few if any lipid droplets or vacuoles. Unlike Sertoli cell-enriched aggregates in culture, rete testis epithelial cell preparations do not form cytoplasmic extensions, and no associated germ cells are present. Rete cells in culture express cytokeratin and vimentin in the cytoskeleton, whereas Sertoli cells prepared from testes of adult rams contain vimentin but not cytokeratin. Both rete cells and Sertoli cells stain positively for laminin but not for fibronectin, Collagen Type I, or Collagen Type III. The rete cells synthesize and secrete several proteins into the culture medium, evident in gel electrophoresis patterns of radiolabeled proteins. This pattern is similar, but not identical, to that secreted by Sertoli cell-enriched preparations. Rete cells in culture in the presence of serum continue to undergo mitotic division, but Sertoli cells do not. A variety of criteria were employed to estimate the relative numbers of Sertoli cells present in the rete testis epithelial cell-enriched preparations from testes of adult rams, including morphological and ultrastructural differences between the two cell types, and the presence of desmosomal proteins and cytokeratin in rete cells but not in Sertoli cells. The relative number of fibroblast-like cells was determined by measuring the expression of fibronectin and Collagen Type I, and an immunocytochemical probe for the detection of Factor VIII was used to estimate the degree of contamination by vascular endothelial cells. Using these markers, we determined that the rete testis epithelial cell-enriched preparations were about 93% pure. Primary cultures under defined conditions contained relatively few Sertoli cells (0.4%), but were contaminated to a larger extent by fibroblast-like cells (approximately 4%) and by endothelial cells (about 3%). The possible functions of rete testis epithelial cells are discussed herein.

Animals↗

PubMed1987

Biosynthesis and secretion of clusterin by ram rete testis cell-enriched preparations in culture.

Rabbit polyclonal antibodies, directed specifically against clusterin purified from ram rete testis fluid, were employed in an investigation of the biosynthesis of clusterin by cultures of rete testis epithelial cells and by Sertoli cells prepared from testes of adult rams. Cells in serum-free medium were incubated in the presence of either [35S]methionine, [3H]leucine, or [3H]glucosamine, and radiolabeled proteins secreted were immunoprecipitated. The pellet was subjected to polyacrylamide gel electrophoresis under reducing and non-reducing conditions, and the gels were then fluorographed. In other experiments, protein bands were transferred to nitrocellulose and visualized immunochemically. Under non-reducing conditions, a single band was detected, having a molecular weight of 80,000. Under reducing conditions, doublet bands were detected, having approximate molecular weights of 40,000 (major band) and 37,000 (minor band). These properties were indistinguishable from those obtained with authentic samples of pure clusterin subjected to gel electrophoresis and Western immunoblot procedures. Amounts of clusterin synthesized by rete testis cells in culture, quantitatively determined with a sandwich enzyme-linked immunosorbent assay procedure, were approximately 4 micrograms/micrograms cell DNA/48 h. Immunocytochemical localization investigations, using monoclonal antibodies against clusterin, revealed the presence of clusterin in the perinuclear of juxtanuclear regions, in both rete testis epithelial cells and Sertoli cells in culture. The possible functions of clusterin produced by rete testis epithelial cells and by Sertoli cells are discussed.

Animals↗

PubMed1987

Immunocytochemical localisation of the antibody which breaches the blood-testis barrier in sympathetic orchiopathia.

The phenomenon of sympathetic orchiopathia, in which ischaemia of one testis results in histological damage to the contralateral testis, is now well documented. This study used immunocytochemical techniques to investigate whether this damage is caused by antibody penetrating the "blood-testis" barrier and affecting spermatogenic and supporting cells of the seminiferous tubules. It has been demonstrated that IgM antibodies breach the "blood-testis" barrier of the contralateral testis 7 days after infarction and that they are replaced by IgG antibodies after 28 days. Cells affected are the epithelial cells of the membrana propria, the Sertoli cells and immature spermatogenic cells. Beyond 28 days after infarction no significant amounts of antibody of either class were demonstrated within the seminiferous tubules of contralateral testes.

Animals↗