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PubMed1997

A novel, testis-specific mRNA transcript encoding an NH2-terminal truncated nitric-oxide synthase.

mRNA diversity represents a major theme of neuronal nitric-oxide synthase (nNOS) gene expression in somatic cells/tissues. Given that gonads often express unique and biologically informative variants of complex genes, we determined whether unique variants of nNOS are expressed in the testis. Analysis of cDNA clones isolated from human testis identified a novel, testis-specific nNOS (TnNOS) mRNA transcript. A predicted 3294-base pair open reading frame encodes an NH2-terminal truncated protein of 1098 amino acids. Measurement of calcium-activated L-[14C]citrulline formation and nitric oxide release in CHO-K1 cells stably transfected with the TnNOS cDNA indicates that this protein is a calcium-dependent nitric-oxide synthase with catalytic activity comparable to that of full-length nNOS. TnNOS transcripts exhibit novel 5' mRNA sequences encoded by two unique exons spliced to exon 4 of the full-length nNOS. Characterization of the genomic structure indicates that exonic regions used by the novel TnNOS are expressed from intron 3 of the NOS1 gene. Although lacking canonical TATA and CAAT boxes, the 5'-flanking region of the TnNOS exon 1 contains multiple putative cis-regulatory elements including those implicated in testis-specific gene expression. The downstream promoter of the human nNOS gene, which directs testis-specific expression of a novel NH2-terminal truncated nitric-oxide synthase, represents the first reported example in the NOS gene family of transcriptional diversity producing a variant NOS protein.

Alternative Splicing↗
PubMed1997

Ontogeny and localization of an oncostatin M-like protein in the rat testis: its possible role at the start of spermatogenesis.

Oncostatin M (OSM), a member of the interleukin 6 family of cytokines, was found to be highly expressed in the late fetal and early neonatal rat testis, as well as in the maturing and adult testis. Two different forms of OSM were observed, one of M(r) 22,000 and the other of M(r) 36,000. In the prepubertal rat testis [19 days post coitum, 8 days post partum (dpp), and 15 dpp], the form with the higher molecular weight prevailed, whereas in the maturing testis (30 dpp, 45 dpp, and 12 weeks post partum), a shift toward the lower molecular weight form was observed, as well as a decrease in its relative amount. By immunohistochemistry on testicular sections, OSM-specific immunostaining was observed in the interstitial tissue at every age studied. In contrast, OSM immunoreaction was localized in the Sertoli cells exclusively around the start of spermatogenesis, being strongest at 3 dpp. In vitro studies revealed that neonatal Sertoli cells produce OSM. The possible role of OSM at the start of spermatogenesis was investigated by using a coculture of Sertoli cells and gonocytes isolated from newborn rats. OSM significantly increased the survival of both Sertoli cells and gonocytes in a dose-dependent manner. The proliferative activity of the Sertoli cells was not affected by OSM, whereas that of gonocytes was increased by almost 60% after 6 days of culture. Comparison of the effect of OSM on these cocultures with other members of the interleukin 6 family of cytokines demonstrated that this factor is more potent than leukemia inhibitory factor or ciliary neurotrophic factor. On the basis of these findings, it can be concluded that OSM is present in the rat testis, and it is likely to play an important role at the start of spermatogenesis.

Animals↗
PubMed1977

Radiation damage to mouse testis cells from [99mTc] pertechnetate.

The radiation dose and the biologic damage to mouse testis from intravenously administered [99mTc] pertechnetate were studied. The dose was measured for penetrating radiations from Tc-99m, using calibrated thermoluminescent dosimeters and calculations from the uptake of the nuclide in the testis, and was found to be 4.9 rada per mCi of Tc-99. The biologic damage was measured by the decrease in the number of sperm heads in the testis, counted both by hemacytometer and by Coulter counter. In preliminary experiments using external gamma radiation from Cs-137, the number of sperm heads reached a minimum 29 days after irradiation. Twenty-nine days after injection of 5.8 mCi of Tc-99m, which gives 28 rads to the testis, the number of sperm hads decreased to 70% of control. The biologic effect corresponds to that seen after 40 rads of gamma radiation from Cs-137. The damage to mouse testis cells from internally administered Tc-99m as measured in an in vivo system appears to be at least as significant as that from external gamma irradiation, if not more so.

Animals↗
PubMedDate not supplied

Differential methylation in steroid 5 alpha-reductase isozyme genes in epididymis, testis, and liver of the adult rat.

DNA methylation has been largely involved in the regulation of tissue-specific gene expression. The aim of the study was to determine the methylation pattern of steroid 5 alpha-reductase genes 1 and 2 in two reproductive tissues (testis and epididymis) and a nonreproductive tissue (liver) that exhibit different contents of steroid 5 alpha-reductase isozymes. These isozymes induce the bioconversion of testosterone to dihydrotestosterone that in mammals is a key molecule for external genitalia development. Genomic DNA from the testis, the epididymis, and the liver from normal adult rats was used to determine cytosine and adenine methylation pattern of steroid 5 alpha-reductase genes 1 and 2 by restriction fragment length polymorphism (RFLP) analysis using restriction enzymes sensitive to adenine (Mbo I and Sau3A I) and cytosine (Hpa II and MSP I) methylation. We also evaluated the expression of both steroid 5 alpha-reductase genes by northern blot. When genomic DNA was digested with Hpa II or Msp I, we found that steroid 5 alpha-reductase gene 2 was less cytosine methylated in the epididymis and in the testis than in the liver. In contrast, when genomic DNA was digested with Mbo I or Sau3A I, we observed that gene 2 was more adenine methylated in the epididymis and in the testis than in the liver. 5 alpha-Reductase gene 1 presented the same adenine- and cytosine-methylation pattern in the studied tissues. We also found a differential expression of steroid 5 alpha-reductase genes. Gene 2 was expressed both in the testis and the epididymis but not in the liver; whereas gene 1 was only expressed in the latter. Our results suggest that the differential methylation pattern in 5 alpha-reductase gene 2 in reproductive and nonreproductive tissues should be involved in the regulation of its expression.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1997

Laparoscopy for the impalpable testis.

BACKGROUND: Use of laparoscopy in the management of the impalpable testis remains controversial. Localization of the testis may help plan or obviate the need for groin exploration. This study reviews the need for inguinal exploration with respect to laparoscopic findings, particularly of vas and vessels entering a closed deep inguinal ring. METHOD: Case notes of boys undergoing laparoscopy for undescended testes were reviewed retrospectively. RESULTS: Of 86 impalpable testes, 32 were intra-abdominal and ten were absent with intra-abdominal blind ending vas and vessels. In 17 instances the vas and vessels entered an open internal ring and in 26 a closed internal ring. In one boy neither vas, vessels nor testis were visualized. Of the 26 impalpable testes with a closed internal ring, excision of testicular remnants in 18 revealed no histological testicular parenchyma, one boy had bilateral perineal ectopic testes missed clinically and six were not explored. CONCLUSION: The laparoscopic finding of vas and vessels entering a closed deep inguinal ring should prompt a careful examination for an ectopic testis. If a palpable testis can be ruled out, inguinal exploration is not necessary, as viable testicular parenchyma is rarely found. Laparoscopy would have avoided negative exploration in 42 per cent of impalpable testes in this series.

Adolescent↗
PubMed1993

Hypersensitivity of human testis-tumour cell lines to chemotherapeutic drugs.

Metastatic testis tumours, in contrast to most other types of cancer, can be cured by drugs. To investigate which classes of chemotherapeutic drug are differentially toxic to testis-tumour cells, we compared the in vitro dose-response curves of 5 human testis and 5 bladder-cancer cell lines to 12 compounds. The testis cells were hypersensitive to drugs that interact directly with DNA (m-amsa, bleomycin, cisplatin, doxorubicin, methylnitrosourea, mitozolomide, etoposide, mitomycin-C), but little or no difference between the 2 cell types was seen following exposure to drugs whose mechanisms of action do not involve direct interaction with DNA (methotrexate, 5-fluorouracil, colchicine, vinblastine). We conclude that testis tumour cells are either less tolerant of, or have a reduced capacity to repair, DNA damage.

Antineoplastic Agents↗
PubMed1989

CT and MR imaging of malignant germ cell tumor of the undescended testis.

Preoperative localization of the impalpable undescended testis is necessary to facilitate proper surgical planning. There is an increased incidence of malignant change in the undescended testis; demonstration of malignancy before surgery will significantly alter the treatment. We describe the computed tomographic (CT) and magnetic resonance (MR) findings in 2 patients with malignant change in an intraabdominal testis. The CT scan revealed lesions with areas of low density, 1 of which had focal calcifications; MR revealed lesions of predominantly low or intermediate signal intensity on both long and short TR/TE images, with some areas of very high signal on both sequences. After initial management with chemotherapy, the residual tumor was surgically resected. In neither instance was residual normal testis demonstrated. Both CT and MR are ideal methods of examining malignant transformation of the undescended testis, because of their ability to characterize the internal structure of the organ and, in the case of MR, its capacity for multiplanar imaging. They are almost of equal value except for the ability of CT to identify calcification and of MR to diagnose hemorrhage.

Adult↗
PubMed2004

High scrotal (Bianchi) single-incision orchidopexy: a "tailored" approach to the palpable undescended testis.

Our aim was to evaluate the utility of the high scrotal orchidopexy (Bianchi) approach for palpable undescended testis (UDT) and to assess long-term follow-up. We reviewed the records of orchidopexies performed between 1999 and 2002. The patients were then categorized by intraoperative exam under anesthesia as to whether their testes were palpable or nonpalpable. All palpable UDT that were initially thought to be amenable to a single high scrotal approach (Bianchi) were then reviewed. These cases were then analyzed to assess the impact of patient age, initial location of the testis, and prior inguinal/scrotal surgery with respect to the necessity to convert to a standard two-incision technique, and to analyze success and complications at 6-12-week and 1-year follow-up. Two hundred and nineteen orchidopexies were performed on 204 patients over this 4-year period. There were 178 testes palpable, and the transscrotal approach was used in 85 patients (100 orchidopexies). The preoperative positions of the testes that were thought to be amenable to Bianchi technique included the following: gliding (19), secondary trapped (25), superficial inguinal pouch (42), and location within the inguinal canal (2), while the remaining 12 testes were ectopic. Six patients required conversion to a traditional inguinal approach because of insufficient cord length via the single incision to allow the testis to lie in the scrotum. All patent processes vaginalis were ligated via the scrotal incision, regardless of their size. All patients, except for one who had a testis in the superficial inguinal pouch, had palpable testes of stable size and in a dependent position at 6-12-week follow-up. Of the 62 children who returned for 1-year follow-up, all had findings identical to those at their initial 6-week visits, with no atrophy or secondary reascent. Postoperative complications included transient postoperative scrotal hematoma in a single patient. The single failure underwent a successful two-incision orchidopexy for secondary reascent and a resultant trapped testis. Children with primary palpable undescended, gliding, or trapped testes can be managed successfully through the transscrotal route in the majority of cases. With use of a tailored approach to the palpable UDT, an additional groin incision is necessary only for a minority of appropriately selected cases.

Adolescent↗
PubMed2006

A case of immature teratoma originating in intra-abdominal undescended testis in a 3-month-old infant.

Teratomas in an undescended testis are rare in infants. This report was the youngest case of immature teratoma originating in intra-abdominal undescended testis. A 3-month-old infant with cryptorchism was seen because of an asymptomatic palpable mass in the right abdomen. Ultrasonography and computed tomography revealed a multicystic large tumor with focal calcifications in the right side and serum tumor markers within normal limits. Complete resection of the tumor was performed and the histopathological diagnosis was made as immature teratoma of the right testis. Because retroperitoneal lymph nodes metastasis was observed in 3-month follow-up postoperatively, retroperitoneal lymphadenectomy and chemotherapy including bleomycin, etoposide, and cisplatin were performed. Presently, the infant has been free of recurrence for 3 years. We suggest that nonpalpable testis should undergo a careful evaluation and prompt resolution and that the subsequent finding of an intra-abdominal mass should make us think on the possibility of intra-abdominal testicular germ cell tumor. Postoperative adjuvant chemotherapy in combination with complete resection of the tumor is necessary for pediatric immature teratomas originating in intra-abdominal undescended testis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Laparoscopic orchiopexy without division of the spermatic vessels: can it be considered the procedure of choice in cases of intraabdominal testis?

BACKGROUND: Several surgical procedures have been described for the management of nonpalpable testis. Following a vast experience with a complete laparoscopic two-stage Fowler-Stephens procedure, we report our experience with laparoscopic orchiopexy performed without dividing the spermatic vessels. METHODS: Over a 24-month period, 70 boys with nonpalpable testes (72 overall) underwent laparoscopic diagnostic exploration. Twenty patients (27.8%) of this series who showed an intraabdominal testis underwent laparoscopic orchiopexy without sectioning the spermatic vessels. In seven cases, the testis was just proximal to the internal inguinal ring; in 13, it was in the high intraabdominal position. The technique consisted in sectioning the gubernaculum (when present), opening the peritoneum laterally to the spermatic vessels, and mobilizing the testicular vessels and the vas deferens in a retroperitoneal position for 8-10 cm. The testis was then brought down into the scrotum through the internal inguinal ring (11 cases), if this was open, or through a neo-inguinal ring (nine cases) created medially to the epigastric vessels. In every case, we closed the inguinal ring at the end of the operation using one or two detached sutures. RESULTS: Operating time ranged between 40 and 75 min (median, 55). All the testes were successfully brought down into the scrotum. We had only one (5%) intraoperative complication. In the second patient treated with this procedure, there was an iatrogenic rupture of the spermatic vessels due to excessive traction. CONCLUSION: On the basis of our experience, we believe that laparoscopic orchiopexy without division of the spermatic vessels should be the treatment of choice in the management of nonpalpable testes, because it does not affect normal testicular vascularization and is minimally invasive. A blunt dissection and a delicate manipulation of the testis without excessive traction are the best ways to avoid any kind of complication.

Child↗
PubMed2006

Immunohistochemical localization of galectin-3 in boar testis and epididymis.

The presence and distribution of galectin-3, a beta-galactoside-binding protein, in boar testis and epididymis was studied. Western blot analysis detected galectin-3 in boar testis and epididymis. In particular, intense galectin-3 immunoreaction was seen in the tail of the epididymis, while it was moderate in the head and body. Galectin-3 immunolabelling was detected in the connective tissues of the testis. In the testis, galectin-3 was detected in some cells (presumably peritubular myoid cells), but not in Leydig cells or the cells of the seminiferous tubules. In the epididymis, the galectin-3 immunoreactivity in the connective tissues was the same as in the testis. Intense galectin-3 immunolabelling was seen in the covering epithelium of the epididymis tail, but in very few cells in the head and body. We postulate that galectin-3, immunodetected here in the connective tissues in the male reproductive organs, serves as an extracellular matrix. Furthermore, we postulate that intracellular galectin-3 in the epithelium of the epididymis tail plays a role in either the maintenance of the epithelium or as a source of galectin-3 in the seminal fluid; here it may play a role in sperm activation in the boar reproductive system.

Animals↗
PubMed2004

Scrotal incision orchiopexy for undescended testis.

OBJECTIVES: To evaluate prospectively the success of scrotal incision orchiopexy (Bianchi technique) with or without inguinal hernia in patients with an undescended testis within the inguinal canal or beyond the external inguinal ring. METHODS: A total of 72 orchiopexies were performed in 56 patients with a primary undescended testis. The testicular position and size were assessed again at 1 year of follow-up. RESULTS: A total of 56 patients had bilateral (n = 14), right (n = 26), and left (n = 18) primary undescended testes. Scrotal orchiopexy was attempted in 72 testes and was successful in 68; the remaining 4 patients required conversion to traditional inguinal orchiopexy because of inadequate mobilization. In 34 children (43 testes), the testis was distal to the external inguinal ring (group 1). Scrotal orchiopexy was performed successfully in 42 testes in this group, and only 1 patient required conversion to a traditional inguinal incision. The average operating time was 18 minutes. In 22 children (29 testes), the testis was located within the inguinal canal (group 2); 3 cases required conversion to traditional inguinal orchiopexy. The average operative time was 25 minutes in group 2. All patients had satisfactory scrotal placement with at least one follow-up examination. CONCLUSIONS: A scrotal incision for a palpable primary testis is well tolerated, cosmetically pleasing, and associated with a short operative time.

Child↗
PubMed1998

Laparoscopic orchiopexy: procedure of choice for the nonpalpable testis?

PURPOSE: Multiple approaches exist for the management of the nonpalpable testis. With the use of diagnostic laparoscopy widely accepted in the setting of the nonpalpable testis we have found laparoscopic orchiopexy to be an efficient and logical extension. To evaluate its use we report our experience with laparoscopic orchiopexy to treat 44 nonpalpable testes in 36 patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients who underwent laparoscopic orchiopexy for a 2 1/2-year period. Modifications of the surgical technique are described. RESULTS: The left testis was affected in 18 boys, the right in 9 and both in 9. At laparoscopy 8 testes were at the internal ring or were peeping and the remainder were intra-abdominal. One patient underwent a unilateral 1-stage Fowler-Stephens orchiopexy, and 3 unilateral and 1 bilateral 2-stage Fowler-Stephens orchiopexy. Two patients underwent laparoscopically assisted orchiectomy. The remaining 31 patients underwent laparoscopic orchiopexy without division of the spermatic vessels. At followup (mean 6 months) all testes are without atrophy, and 39 of 42 (93%) are in an acceptable scrotal position. There are 3 testes (7%) high in the scrotum. CONCLUSIONS: Laparoscopic orchiopexy is a logical extension of diagnostic laparoscopy for the evaluation and treatment of the nonpalpable testis. The low incidence of complications and 93% success rate underscore the feasibility of this procedure. It is our procedure of choice for the treatment of nonpalpable testis.

Child↗
PubMed1997

Cystic dysplasia of the rete testis: a benign congenital lesion associated with ipsilateral urological anomalies.

PURPOSE: Cystic dysplasia of the rete testis is a benign congenital lesion that can mimic testicular cancer. We report 6 cases, review the literature, discuss the embryological etiology and make management recommendations. MATERIALS AND METHODS: The records and pathology reports of 6 boys presenting with cystic dysplasia of the rete testis at 5 institutions were reviewed, as was the relevant literature. RESULTS: Of the 6 cases 5 presented as scrotal masses in previously healthy boys and 1 as an abdominal mass in a newborn with multiple congenital anomalies. One patient had been followed from birth for a multicystic dysplastic kidney and 4 were found to have an ipsilateral absent kidney during evaluation. Development of the contralateral side was normal in most cases. CONCLUSIONS: Cystic dysplasia of the rete testis is an unusual, benign congenital lesion that can mimic testicular cancer in presentation. The presence of ipsilateral renal anomalies, particularly renal agenesis, can suggest cystic dysplasia of the rete testis in the differential diagnosis preoperatively. Even if cystic dysplasia of the rete testis is suspected, we recommend inguinal exploration and early control of the spermatic cord in the event that neoplasia is identified. If possible, the goal of preserving as much normal testicular parenchyma as possible is desirable. Long-term followup for possible recurrence is recommended, particularly after local excision.

Child↗
PubMed1989

Laparoscopy: its selected use in patients with unilateral nonpalpable testis after human chorionic gonadotropin stimulation.

Laparoscopy has been used to help evaluate patients with a unilateral nonpalpable testis. This procedure can be performed quickly just before exploration with the patient under the same anesthetic. With laparoscopy it has been possible to localize either a testis or the course of the spermatic vessels in 100 per cent of the patients. Preoperative knowledge of testis location is helpful to plan the location of the incision as well as the type of repair. The incidence of vanishing testis in our series is much higher than that reported previously. This difference is attributed to a careful examination with the patient under anesthesia and preoperative treatment with human chorionic gonadotropin, which made many testes palpable. These results indicate that laparoscopy can be performed safely and quickly, and that it is helpful to manage patients with a unilateral nonpalpable testis.

Adolescent↗
PubMed1983

Ultrasonography of testis tumors.

Intratesticular masses can be identified with a high degree of accuracy using recently refined techniques of scrotal ultrasonography. In an attempt to correlate sonographic findings with histopathologic features the sonograms performed on 17 consecutive patients with testis tumors were reviewed. Two distinct categories were identified. Seminomas and lymphomas appeared hypoechoic and homogeneous, and had sharply demarcated intratesticular borders. Nonseminomatous germ cell tumors, although also of lower echogenicity than normal testis, appeared to have cystic spaces, acoustic shadowing and irregular margins extending into the testis parenchyma. Preoperative characterization of a scrotal mass with ultrasound can facilitate surgical excision of the tumor. Scrotal ultrasonography also is useful in the detection of tumor in a palpable normal testis and is a convenient method for the examination of patients who have had a testis tumor previously.

Adult↗
PubMed1998

Long-term side effects of treatment for testis cancer.

Patients newly diagnosed with testis cancer can now expect excellent results with respect to long-term, disease-free survival after treatment. Given the young age of presentation for many of these patients, the long-term consequences of curing testis cancer have become a major concern. Surgery, radiation, and chemotherapy for testis cancer have all been associated with potential long-term side-effects. Consequently, new treatment regimens have been directed toward minimizing these possible side-effects while at the same time maintaining high cure rates (i.e., limiting the size of radiation fields, decreasing the number of chemotherapy cycles, eliminating bleomycin). Patients and physicians must be made aware of the potential adverse side effects of treatment for testis cancer. At the present time, however, it appears that the beneficial effects of such treatment, with respect to overall and disease-free survival, far outweigh the limited probability of persistent treatment-related side effects in patients newly diagnosed with testis cancer.

Antineoplastic Agents↗
PubMed1997

Complementation analysis of testis tumor cells.

Testis tumors are cured using cisplatin-based chemotherapy in over 80% of patients, and sensitivity to cisplatin is retained by testis tumor cells in vitro. The aim of this study was to use complementation analysis to determine how many genes control sensitivity to cisplatin in testis tumor cells. Four testis tumor cell lines were transfected with pSV2NEO and pBABE plasmids, conferring G418 and puromycin resistance, respectively. Self-crosses were generated to control for gene dosage, and the parentage of the hybrids was confirmed by PCR amplification of VNTR regions. Karyotyping confirmed that all the hybrids retained at least 88% of the combined number of chromosomes of the two parental cell lines. Cisplatin sensitivity was measured by clonogenic assay and complementation was not observed. This finding provides evidence that there is a single common mechanism controlling cisplatin sensitivity in testis tumor cells.

Antineoplastic Agents↗