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Evaluation of the human testis and its age-related dysfunction.

The human testis has been evaluated by its endocrine function, daily sperm output in ejaculates, general appearance of seminiferous tubules, differential cell counts in the testis, and daily sperm production. Within-subject variation for total sperm count in ejaculates is extremely high at 42% to 75% coefficient variation. This variation can be reduced to 12% by averaging the counts obtained for the last three of five daily ejaculates. Plasma FSH concentrations are particularly useful in assessing the status of seminiferous epithelium and/or its Sertoli cell function in infertile men. In aged men, plasma LH, FSH, and estradiol concentrations are higher while plasma testosterone, free testosterone, and the ability of the testis to secrete testosterone following stimulation are reduced. Other age-related changes in human testes include a high incidence of azoospermia, reduced sexual activity, reduced testicular size, impaired spermatogenesis, reduced tubular length, increased thickness of tubular boundary tissue, sclerosis, focal mononuclear orchitis, and dilation of the rete testis. Due to the long duration of the spermatogenic cycle and low numbers of germ cells in human testis, daily sperm production per g parenchyma (efficiency of spermatogenesis) is much lower in humans than in other species. Testicular parenchymal weight, proportion of testis occupied by seminiferous epithelium, volume of seminiferous epithelium, and daily sperm production are significantly reduced in aged men. In various species, including man, germ cell degeneration occurs during spermatocytogenesis, meiosis, and/or spermiogenesis. Germ cell degeneration plays a pivotal role in spermatogenesis, but the mechanisms of degeneration, its etiology, and approaches for its prevention remain unclear.

Adult↗

[Dissociation of testis and epididymis in incomplete descent].

Failure of fusion between testis and epididymis will usually be encountered during operations for undescended testis in children and for infertility in adults. In 325 groin dissections for undescended testis monorchism was diagnosed in 3.7% and nonfusion of testis and epididymis in 1.2%. Case reports of three unilateral and one bilateral conditions are presented. Intraoperative misjudgement of this condition is likely to occur if the blind ending epididymis is mistaken for an atrophic testis. Careful search for the missing testis is mandatory.

Adolescent↗

[Injuries of the testis in children].

Thirty three blunt testicular injuries have been observed within the frame work of the French Society of Pediatric Surgery. Four histological stages are described. Stage 1: testis contusion: 17 cases. Stage 2: rupture and retraction of the albuginea: 10 cases. Stage 3: complete testis rupture: 4 cases. Stage 4: testis fragmentation: 2 cases. Diagnosis remains clinical in spite of the recent progress of ultrasonography. After surgical treatment results show: 9% castration, 25% testis atrophia, that is to say one testis out of three is lost after traumatism. The hormonal function was not affected. 2 Testis biopsies allowed us to study spermatogenesis. There is no proof of astheno or azo or teratospermia after childhood traumatism. Sterility by autoimmunization has been mentioned only in adults.

Adolescent↗

[3 beta-Hydroxysteroid-dehydrogenases of the testis and epididymis of the Peking duck (Anas platyrhynchos L.)].

This study is concerned with the histochemical activity of hydrosteroid dehydrogenases (HSD), glucose-6-phosphate dehydrogenase (G6PDH), and 6-phosphogluconate dehydrogenase (6PGDH) in testis and epididymis of 20 male Pekin ducks. Various 3 beta-HSD, the G6PDH, and the 6PGDH were localized in these organs. 3 beta-etiocholane was much quicker utilized by the 3 beta-HSD than epiandrosterone, dehydroepiandrosterone, and androstendiol. The capability of testis Leydig cells of utilizing the 3 beta-etiocholane was higher in winter than in summer. The G6PDH and the 6PGDH in the Leydig cells and basal cell layer of the tubuli seminiferi contorti were active throughout the year. There was weak 3 beta-HSD activity in the epithelia of the ductuli efferentes distales and in the ductus epididymidis from March to June. The G6PDH and the 6PGDH showed positive reaction in the rete testis and ductuli efferentes proximales throughout the year. The 3 beta-HSD activity in testis and epididymis is saisonally different: In summer, there is no 3 beta-HSD activity in both organs. In winter, the 3 beta-HSD is demonstrable in the testis but not in the epididymis. In spring, there is 3 beta-HSD activity in the epididymis but not in the testis.

3-Hydroxysteroid Dehydrogenases↗

[Morphological changes in the contralateral testis in patients with testicular tumor].

Biopsy of contralateral testis of 20 patients with an unilateral testicular tumor was carried out to evaluate the morphological changes of the contralateral testis caused by the tumor. Serum beta-chorionic gonadotropin (beta-hCG), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and alpha-fetoprotein (AFP) levels before orchiectomy were examined as a function influencing morphological changes of the contralateral testis. Typical carcinoma in situ was found in a case of ipsilateral testis. The presence of a few atypical germ cells, however, was the only finding of the contralateral testis of three patients. Five of 20 patients revealed hypospermatogenesis in the contralateral intact testis. Most of the other patients also showed sloughing of germinal epithelium suggesting disorder of spermatogenesis. Johnsen's mean score count and tubular wall thickening were related to neither clinical stages, ESR, serum beta-hCG, AFP, LH nor FSH levels. Tubular wall thickening was observed in 8 of 10 patients with a tumor weighting over 150 g, but was found in only 1 of 10 patients with a lighter tumor (p less than 0.01).

Adult↗

[Development of the seminiferious tubules and rete testis during the prenatal period of human ontogenesis].

The sources of origin and the peculiarities of formation of the seminal ducts and rete testis during the prenatal period of ontogenesis in man were studied. It has been established that the seminal duct sand the ducts of the rete testis form from the cellular cords of the coelomic epithelium and the primordial germ cells which appear simultaneously in the septum of the testis and the primordial germ cells which appear simultaneously in the septum of the testis and central part of its parenchyma in the embryos, 13.0--17.0 mm long. By plastic and graphic reconstruction, as well as by methods of subtle preparation under binocular microscope MBC-I control it was revealed that the seminal ducts anastomosed between themselves both within the limits of one and the adjacent lobules. The ducts of the rete testis do not form anastomoses, but superimpose over one another, creating an impression of a rete. Approaching the tunica albuginea they merge, continuing into the cuctuli efferentes testis.

Humans↗

[Perineal testis: report of two cases].

Perineal testis is a very rare congenital anomaly. Since the first case of the disease reported by John Hunter in 1786, more than 113 cases have been reported in the English literature, and 13 cases have been reported in the Japanese literature. The 14th and 15th cases are presented herein. Case 1 was a 38-year-old man who came to our clinic with the chief complaint of discomfort of the perineum. Physical examination revealed emptiness of the left scrotal contents and there was a small hen's-egg growth mass corresponding to the normal testis at the left side of the perineum. Excretory urogram showed no abnormality. Orchiopexy to the left scrotum was performed. On surgical exploration the gubernaculum testis was found obviously fixed to the perineum. Histologic examination of the biopsied ectopic testis revealed mild hypospermatogenesis. Case 2 was a 2-year-old boy who was referred to our clinic with the chief complaint of emptiness of the right scrotal contents. Physical examination revealed a bean-sized mass corresponding to the normal testis at the right side of the perineum. Orchiopexy to the right scrotum was performed. On surgical exploration the gubernaculum testis was found to be fixed to the perineum.

Adult↗

[Clinical studies on varicocele. (1). Findings on semen and testis].

The semen and testicular histology of 39 patients with varicocele on the left side, and who had high ligation of the internal spermatic vein at our Department between 1975 and 1981 was examined. The grade of varicocele was neither related to density nor motility of the sperm, nor to the score count of the left testis. In 40% of the patients, both density and motility of the sperm improved after the surgical treatment. In 80% of the patients, the left testis weighed less than the right testis. In most of the patients, the score count of both testes was lower than normal, and was found to decrease remarkably in testes weighing less than 10 g. In 30% of the patients, the score count of the left testis was lower than that of the right testis. A positive correlation was recognized between score count and testicular weight, and no correlation was found between the score count of the right testis and sperm density.

Adolescent↗

Anatomical findings of the vanishing testis.

Inguinal exploration of 62 clinically impalpable undescended testes reveals 40 (64%) instances of absent testis. Nine (22.5%) of the 40 explorations showed complete absence of the testes along with the epididymis and vas deferens, six (15%) were associated with only vas ending blindly, and the other 25 (67.5%) were associated with blind-ending vas deferens and blood vessels: the "vanishing testis syndrome." The anatomical findings of these vanishing testes showed the presence of a vas deferens and vessels lying side by side in the inguinal canal. In Addition, two patients with bilateral vanishing testis were found to be a normal 46 xy phenotypic male. Since testicular tissue is necessary in utero to stimulate external genital development, these findings, imply that testes vanished at some point following induction of masculinization, possibly as a result of an intrauterine vascular accident or testicular torsion. Also, according to the anatomical findings of vanishing testis, it gave us the signal to terminate the exploration when we found absent testis with a blind-ending vas plus vessels on one or both side in an operation for impalpable testis.

Child↗

[A case of an ectopic testis in the perineum].

The ectopic position of the testis is defined by a migration differing from the normal descent into the scrotum. This error is due to an anomaly of fixation of the distal extremity of the gubernaculum testis (2), resulting in an abnormal position of the testis. The five major sites of ectopic testis are the superficial inguinal canal (most frequent), femoral canal, suprapubic region (at the base of the penis), contralateral scrotum (rare) (3) and, lastly, the perineal region, which is also rare (8). The authors report a case of perineal testis in a 4 year old boy. The diagnosis was clinical and was confirmed by ultrasonography. Doppler studies visualised the testicular blood supply. The testis was surgically relocated in the scrotum.

Child, Preschool↗

Expression of cyclin-dependent kinase 5 and associated cyclins in Leydig and Sertoli cells of the testis.

In this study, we examined the expression and subcellular localization of cyclin-dependent kinase 5 (Cdk5), cyclin D1, and cyclin E in Leydig and Sertoli cell lines that were cultured with 7.5, 1.0, 0.5, or 0% serum (mixture of a 2:1 ratio of horse serum and fetal bovine serum) and in the developing rat testis to verify the possible functions of Cdk5, cyclin D1, and cyclin E in the testis. The abundance of Cdk5 and cyclin E in the Leydig cell line, TM3, was significantly reduced at low serum concentrations. In contrast, serum concentration had no effect on Cdk5 and cyclin E levels in the Sertoli cell line, TM4. Cyclin D1 was detected by western blot analysis in TM4 cells only, and its abundance was serum dose dependent. The kinase activity of Cdk5 in TM3 and TM4 cells that were cultured at various serum concentrations coincided with the levels of Cdk5 expression. Immunohistochemical staining for Cdk5 and cyclin E revealed nuclear and cytoplasmic distribution, both in TM3 and TM4 cells. Moreover, cyclin D1 immunoreactivity was only detected in TM4 cells. In the developing rat testis, Cdk5 expression was most prominent at 2 and 3 weeks after birth. Cyclin D1 was strongly expressed at 1 and 2 weeks in premature rat testes. On the other hand, cyclin E was highly expressed in the adult testis. Immunohistochemical localization of Cdk5, cyclin D1, and cyclin E in 1-week-old and adult rat testes revealed expression in both Leydig and Sertoli cells. Our results suggest that Cdk5 in TM3 and Leydig cells of the testis might play a role in cell cycle regulation, whereas Cdk5 in TM4 and Sertoli cells of the adult testis might have some additional functions besides control of proliferation.

Animals↗

Continuing increase in incidence of germ-cell testis cancer in young adults: experience from Connecticut, USA, 1935-1992.

The current study is designed to examine long-term trends by histologic types of testis cancer in Connecticut. A regression model was used to identify age, period, or cohort as determinants of the time-trend on histologic types of testis cancer. The results from this descriptive epidemiologic study show that the overall age-adjusted incidence rate of testis cancer has increased 3.5-fold in Connecticut during the past nearly 60 years of cancer registration. The rates for seminoma and non-seminoma have been increasing since the mid-1950s and increase in a similar manner for those aged 15 to 49. The largest increase was observed in the age groups 20 to 44 for seminoma and 15 to 34 for non-seminoma. The observed increase was limited to whites. The results from age-period-cohort modeling suggest that the observed increase in seminoma before 1950s could be largely attributable to a period effect, while the increase for cohorts born after about 1910 both for seminoma and for non-seminoma are mainly explained by a strong birth-cohort effect. Therefore, the observed increase in germ-cell testis cancer in this population is likely to continue in the coming years. Thus far, the proposed hypotheses, such as exposure to DES in utero, earlier lifetime exposure to viruses, trauma or unusual amounts of heat to the testis, cannot adequately explain the observed incidence patterns of testis cancer. Analytical epidemiologic studies with large sample size are urgently needed to examine the risk factors responsible for the increase.

Adolescent↗

Carcinoma in situ of the testis in infertile men. A histological, immunocytochemical, and cytophotometric study of DNA content.

Of 723 infertile men (128 with a history of cryptorchidism) whose testes were biopsied at the outer lateral face of the testis, five presented carcinoma in situ (CIS) in one testis. These testes were removed, serially sectioned, and examined by light microscopy. In order to evaluate whether only one or two biopsies are sufficient to diagnose CIS, before sectioning the testes four biopsies were taken at the anterior face, posterior face, superior pole, and inferior pole of the testis, respectively. Two of the five men had undergone orchiopexy in infancy and the testis contained tubules with Sertoli cells and isolated spermatogonia. CIS was also present in some tubules that were principally located near the rete testis. Of the four simulated biopsies, only that performed at the posterior face of the testis revealed CIS. The other three infertile men showed tubules with complete, although reduced, spermatogenesis, and tubules lined by Sertoli cells only. CIS was found in both types of tubules. These tubules with CIS formed lobules that extended throughout the testicular parenchyma. Most simulated biopsies performed in these three testes showed CIS. The average nuclear DNA content of CIS cells was about 4c in all testes. This content was similar both in tubules with complete spermatogenesis and in tubules with Sertoli cells only.

Adult↗

The mouse Tsx gene is expressed in Sertoli cells of the adult testis and transiently in premeiotic germ cells during puberty.

Tsx is a gene of unknown function that was previously shown to be expressed specifically in the testis. In order to gain insight into the function of Tsx its pattern of expression was characterized with regard to both timing and cell type in the testis. Northern blot analysis of early postnatal testes showed not only that Tsx message was detectable shortly after birth, but that it increased substantially between 7 and 12 days postpartum (dpp), roughly coincident with the onset of meiosis in the mouse. Alternative Tsx transcripts, detected by RT-PCR, included a spliced form that first appeared at around 12 dpp. In situ hybridization revealed Tsx signal in the somatic Sertoli cells of the adult testis. Consistent with the data from Northern blots, in situ hybridization signal was first detectable in normal pubertal testes at 12 dpp. An anti-Tsx polyclonal antiserum specifically stained premeiotic germ cells in addition to Sertoli cells of pubertal testes at 16, 19, and 27 dpp. Tsx immunostaining in germ cells was nuclear, while Sertoli cells displayed signal throughout the cytoplasm and nucleus. In the adult, Tsx was detected exclusively in Sertoli cells. In contrast, in the adult testis of the oligotriche (olt) mutant, where spermatogenesis is blocked after meiosis, Tsx protein was still present in the spermatogonial nuclei of a subset of tubules. Taken together, these results demonstrate that Tsx expression is induced in both premeiotic germ cells and Sertoli cells during the first wave of spermatogenesis, but that expression is maintained at a detectable level only in Sertoli cells of the normal adult. The persistence of Tsx expression seen in spermatogonia of the adult olt mutant supports the hypothesis that during the first wave of normal spermatogenesis, the advent of a late-stage cell type, either elongating spermatid or spermatozoan, is responsible for extinguishing expression in spermatogonia in normal adult testis. To our knowledge, Tsx is the first gene to show a pattern of germ cell expression that is apparently specific to the pubertal testis.

Animals↗

Screening for Y microdeletions in men with testicular cancer and undescended testis.

PURPOSE: To investigate a possible association between testicular cancer or undescended testis and Y microdeletions. METHODS: It was designed as a retrospective clinical study. A total of 225 men with testicular cancer or undescended testis were included to study. Fertile men (n = 200) were investigated as a control. Genomic DNA, which was extracted from blood samples were investigated with a fluorescent multiplex PCR protocol for screening for Y microdeletions. RESULTS: A single STS missing was found in eight men; one from the control group (sY153), seven from the patients group. The positive cases showed a single STS missing of marker sY153 and sY139 in testicular cancer (6/185) and undescended testis (1/40) patients, respectively. CONCLUSIONS: Since no contiguous, real Y microdeletions were found in the study population, it seems that Y microdeletions are not a likely common etiological cause of poor spermatogenesis in testicular cancer and undescended testis. However, it remains to be determined whether men having a single STS missing have a risk of developing testis cancer or having undescended testis.

Adult↗

Pagetoid spread of intratubular germ cell neoplasia into rete testis: a morphologic and histochemical study of 100 orchiectomy specimens with invasive germ cell tumors.

Intratubular germ cell neoplasia (ITGCN) is now considered to be the preinvasive phase of testicular germ cell tumors with the exceptions of spermatocytic seminoma, pure yolk sac tumor, and mature teratoma. Pagetoid spread of ITGGN into rete testis is a common yet unpublished finding in these cases. We reviewed 100 cases of testicular germ cell tumors from the Surgical Pathology service of Parkland Memorial Hospital (Dallas, TX) to evaluate the frequency of this pattern of spread. Additional sections were obtained from selected cases and were stained with anti-placental alkaline phosphatase, anti-low molecular weight keratin (clone AE1), and various lectins to highlight the process. Pagetoid spread of ITGCN into rete testis was identified in 24 of 60 cases (40%) in which histologic sections contained both ITGCN and rete testis. The incidence of pagetoid ITGCN involvement of the rete testis was lower in pure seminoma (seven of 25 cases [28%]) than in testes containing nonseminomatous germ cell tumors (17 of 35 cases [49%]). AE1 stained the epithelial cells of the rete testis but not the cells of the ITGCN, whereas placental alkaline phosphatase stained the neoplastic cells but not the epithelial cells of the rete testis. These stains were useful in delineating two cases in which the pagetoid involvement was so extensive that they were misdiagnosed as invasive seminomas. Pagetoid spread of ITGCN is a relatively common finding in testicular germ cell tumors and rarely can be mistaken for invasive seminoma. Immunohistochemistry can be helpful in distinguishing florid pagetoid spread from invasive seminoma.

Adolescent↗

Laparoscopy for evaluation of cryptorchid testis.

Four male patients with a unilateral nonpalpable testis were considered for laparoscopy. Preoperative evaluation by computerized tomography and ultrasonography failed to demonstrate cryptorchid testis. Laparoscopy clearly identified the anatomy in all 4 cases. Two patients had an absent testis, 1 patient underwent orchiectomy for a dysmorphic testis, and 1 patients underwent orchiopexy for a testis located within the inguinal canal. Pediatric laparoscopy is an effective and safe adjunct in the management of cryptorchid testis.

Adult↗

[Is there any interest to perform ultrasonography in boys with undescended testis?].

OBJECTIVE: To evaluate the accuracy of ultrasonographic examination in boys with an undescended testis. MATERIAL AND METHODS: All patients who were referred to the paediatric surgeon after detection of an undescended testis were evaluated prospectively between November 2001 and November 2004. Among these 377 patients, 87 were referred with an ultrasonogram previously prescribed by the referring primary physician. The results of the ultrasonogram were compared to the results of the clinical examination of the paediatric surgeon and, in cases of no palpable testis, to the surgical findings. RESULTS: Ultrasonography did not detect the retractile testes. Ultrasonography detected 67% of the palpable undescended testes. In cases of no palpable testis, the ultrasonographic examination missed the abdominal testes and sometimes other structures were falsely interpreted as a testis. CONCLUSION: Sonography has no place in the diagnosis of undescended testis.

Child↗