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Pathology of 46,XY pure gonadal dysgenesis: absence of testis differentiation associated with mutations in the testis-determining factor.

Individuals with 46, XY pure gonadal dysgenesis present with a completely female phenotype. These individuals develop bilateral streak gonads and have normal Müllerian structures. The apparent absence of testicular tissue in these individuals suggests a mutation in the initial steps of the male sex-determining pathway. A candidate gene for the primary signal in this pathway was recently cloned (SRY) which encodes a protein with a DNA-binding capacity. In a study of 14 XY females with pure gonadal dysgenesis harbouring SRY, we analysed the histology of the gonads and compared it to the presence or absence of mutations in the SRY open reading frame (SRY-orf). The histological analysis revealed two distinct groups of streak gonads. In the first group, the gonad was composed of exclusively ovarian-like stroma, with sclero-hyaline nodules in some areas. No tubules were observed. The gonads in the second group were composed of undifferentiated stroma harbouring either tubules or a rete structure. This suggests that in the latter group some differentiation (towards testis formation) has occurred, whereas in the first group ovarian differentiation has been interrupted. Individuals with mutations in the SRY-orf were found to have streak gonads of the first group, whereas most of the remaining XY females without detectable mutation in the SRY-orf had streak gonads belonging to the second group. On the basis of histology, it may be possible to distinguish between mutations in the sex-determining or sex-differentiation pathways. We suggest that SRY may play a role in rete testis formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Capsaicin in albino rats prevents contralateral testis from the damaging effects posed by ipsilateral testis that underwent torsion.

OBJECTIVE: To evaluate the effect of capsaicin, a powerful neurotoxin selective to afferent nerves, on contralateral testicular damage in ipsilateral testicular torsion. METHODS: Forty male albino rats were randomly allocated into five groups. No operation was performed in group one. After intraperitoneal administration of 0.9% NaCl, rats underwent a sham operation in group 2 and testicular torsion in group 3. In groups 4 and 5 rats underwent sham operation and testicular torsion, respectively after intraoperitoneal capsaicin injection. Contralateral testes were harvested on the fifteenth day of the experiment and mean seminiferous tubular diameters and mean testicular biopsy scores were recorded for each testis. The values were compared through analysis of variance (ANOVA) with Turkey-Kramer multiple comparisons test and p values less than 0.05 were considered to be significant. RESULTS: Mean testicular biopsy scores and mean seminiferous tubular diameters of group 5 was significantly higher than the group 3. There was no difference between the groups 1, 2, 4, and 5 when these two parameters are concerned. CONCLUSION: Capsaicin effectively prevents contralateral testicular damage encountered following ipsilateral testicular torsion. The inhibition of afferent impulses from the ipsilateral testis under distress prevents contralateral testicular injury, and provides additional data to support the role of an autonomic reflex arc in contralateral testicular injury.

Afferent Pathways↗

Identification of the cytochrome P-450 isozymes responsible for testosterone oxidation in rat lung, kidney, and testis: evidence that cytochrome P-450a (P450IIA1) is the physiologically important testosterone 7 alpha-hydroxylase in rat testis.

Previous studies have shown that several forms of cytochrome P-450 present in rat liver microsomes oxidize testosterone with a high degree of regio- and stereospecificity. The aim of this study was to characterize the pathways of testosterone oxidation catalyzed by rat extrahepatic microsomes. Lung, kidney, testis, prostate, and brain were isolated from 3- and 14-week-old-male Sprague-Dawley rats. Microsomes from lung, kidney, and testis catalyzed distinctly different pathways of testosterone oxidation, whereas microsomes from prostate and brain failed to hydroxylate testosterone directly in a time- and protein-dependent manner. Lung microsomes from immature and mature rats converted testosterone to 16 alpha-hydroxytestosterone, 16 beta-hydroxytestosterone, and androstenedione. Lung microsomes were shown by Western immunoblot to contain cytochrome P-450b (P450IIB1), which has been shown previously to catalyze these three pathways of testosterone oxidation. Antibody against cytochrome P-450b strongly inhibited (greater than 80%) androstenedione formation and completely inhibited (greater than 95%) the 16 alpha- and 16 beta-hydroxylation of testosterone catalyzed by lung microsomes (as did carbon monoxide and antibody against NADPH-cytochrome P-450 reductase). Kidney microsomes from mature male rats converted testosterone to 2 alpha-hydroxytestosterone, 16 alpha-hydroxytestosterone, and androstenedione, whereas only the latter pathway was catalyzed by kidney microsomes from immature rats. Kidney microsomes from mature male rats were shown by Western immunoblot to contain cytochrome P-450h (P450IIC11), which has been shown previously to convert testosterone to 2 alpha-hydroxytestosterone, 16 alpha-hydroxytestosterone, and androstenedione. Antibody against cytochrome P-450h completely inhibited (greater than 95%) the 2 alpha- and 16 alpha-hydroxylation of testosterone by kidney microsomes, but had little effect on androstenedione formation, which is catalyzed by 17 beta-hydroxysteroid dehydrogenase. Testicular microsomes from mature, but not immature, rats catalyzed the 7 alpha-hydroxylation of testosterone. Previous studies have shown that this reaction is catalyzed in liver microsomes by cytochrome P-450a (P450IIA1). Testicular microsomes from mature, but not immature, rats were shown by Western immunoblot to contain cytochrome P-450a. Antibody against cytochrome P-450a or NADPH-cytochrome P-450 reductase completely inhibited (greater than 95%) the 7 alpha-hydroxylation of testosterone by testicular microsomes. A 90:10 atmosphere of carbon monoxide and oxygen did not appreciably block the 7 alpha-hydroxylation of testosterone by testicular microsomes, wh

Animals↗

Studies of the human testis. XVIII. Simultaneous measurement of nine intratesticular steroids: evidence for reduced mitochondrial function in testis of elderly men.

To determine the basis for the decline in testosterone production by the aged testis, intratesticular unconjugated steroids, including testosterone, pregnenolone (3 beta-hydroxy-5-pregnen-20-one), 17 alpha-hydroxypregnenolone (3 beta,17 alpha-dihydroxy-5-pregnen-20-one), dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one), androstenediol (5-androstene-3 beta,17 beta-diol), progesterone, 17 alpha-hydroxyprogesterone, androstenedione (4-androstene-3,17-dione), and 17 beta-estradiol, were measured by simultaneous RIAs in 32 previously untreated elderly men (aged 61-85 yr) undergoing orchiectomy as therapy for prostatic carcinoma and 20 young men (aged 25-35 yr) with oligospermia and varicocele. In vitro steroidogenesis using labeled pregnenolone as substrate was also investigated. Serum and intratesticular testosterone levels were lower (P less than 0.05) in aged patients [3.3 +/- 1.9 ng/ml and 0.86 +/- 0.53 microgram/g tissue (mean +/- SD)] than in young men (6.4 +/- 1.9 ng/ml and 1.7 +/- 1.1 microgram/g tissue), while circulating LH levels were higher (P less than 0.05) in elderly men (151 +/- 105 ng/ml) than in the young men (79 +/- 33 ng/ml), indicating that a primary pathological process affects the senescent testis, producing a decline in testosterone production. Study of bioconversion of [3H]pregnenolone to delta 4 steroids, 17 alpha-hydroxysteroids, and C19 steroids as well as analysis of the relative amounts of intratesticular steroids, as determined by RIA, revealed no apparent differences in the process of microsomal steroidogenesis in elderly compared to that in young men. The sum of the nine measured intratesticular steroid concentrations per g tissue wt was significantly lower (P less than 0.05) in aged patients (1.94 +/- 0.93 microgram/g tissue), than in young patients (3.68 +/- 1.90 micrograms/g tissue). The sum of the nine intratesticular steroids measured was positively correlated (P less than 0.01) with circulating LH levels in both patient groups, and the slope of this regression line was 14-fold greater for young men than for elderly men. Since the total concentration of the nine measured steroids reflects the pregnenolone supplied by the mitochondria within Leydig cells, it appears that the decline in Leydig cell function in aged men is attributable to a reduced supply of mitochondrial steroid precursors rather than to an impairment in microsomal steroidogenesis.

Adult↗

[Morphologic and histoenzymologic analysis of effect of electrical fields at 17 khz on testis and testis appendages in mice].

Methods of quantitative morphological and histochemical assay were used to study effects of 9-month electrical exposure (f = 17 kHz, E = 100 kW/m2 for 1 or 4 hrs, 5 d/w) on testis and testis appendages in mice. Exposure in electromagnetic field gave rise to desquamation of spermatogenic epithelial layers in the seminiferous tubes, reduction of the number of testosterone-producing cells, microcirculatory changes, metabolic rearrangements, principally compensatory by nature and aimed to maintain spermatogenesis and steroidogenesis. Results of the experiment suggest accelerated reproductive ageing.

Adaptation, Physiological↗

Testis sparing surgery for epidermoid cyst of the testis: a case report.

A rare tumour of a prepubertal child, an epidermoid cyst, was excised with testicular preservation. Childhood testicular tumours are usually benign. Although epidermoid cysts of the testis may have teratomatous component, testicular teratomas are generally benign in the prepubertal child. For these reasons testis sparing surgery seems applicable in childhood epidermoid cysts.

Child↗

Testis sparing surgery for pediatric epidermoid cysts of the testis.

Epidermoid cyst of the testis is a rare, benign intratesticular tumor in children. Four patients 4 to 15 years old with epidermoid cysts were managed by tumor excision with salvage of the testis. Preoperative ultrasound, tumor marker status and intraoperative findings were suggestive of a benign neoplasm. Under these circumstances epidermoid cysts may be safely treated by excision in prepubertal patients.

Adolescent↗

A new case of malignant mesothelioma of the tunica vaginalis testis. Immunohistochemistry in comparison with an adenomatoid tumor of the testis.

Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor with 41 previously reported cases. The histological and immunohistological features of a new case in an 80-year-old patient are described and compared with an adenomatoid tumor of the tunica vaginalis testis, which is considered to be the benign variant of malignant mesothelioma. Both tumors revealed strong cytoplasmic staining for a panepithelial antibody (Lu-5) and membranous staining for BMA-120 (a mesothelial/endothelial cell marker) but yielded negative staining results with the endothelial cell markers QBend-10 (CD 34), Factor VIII-related antigen (vWF) and UEA-1. There was also negative staining for CEA, Ber-EP4, HEA-125 and Blood group related antigens A, B, H. An identical staining pattern was evident in normal and reactive mesothelial cells. Our data support a mesothelial rather than an endothelial derivation of the adenomatoid tumor studied.

Aged↗

The reproductive imperative: a case report highlighting the possibility of using chemotherapy to conserve the testis in patients with testis cancer.

This report examines the dilemma that a patient, who was a doctor, faced on discovering that he was developing a second primary testicular tumour (seminoma) in a solitary testis. The usual treatment for this is radical orchidectomy. He rejected this on the grounds that he wanted to have children, and eventually decided on the use of single-agent carboplatin chemotherapy. Seventeen months after treatment, there was no evidence of tumour on MRI or ultrasound scanning and there is some recovery of spermatogenesis. So far, 13 of 14 patients treated with chemotherapy for metastatic disease (with the primary tumour being left in situ), which has normalized following treatment, have survived for more than 5 years without evidence of tumour recurrence. This approach could be a viable option for men with tumours in a solitary testis who have not completed their families. However, a larger prospective study is essential to determine whether this approach is safe, so that these patients will not have to bear the psychological burden of choosing between their chances of survival and the possibility of fathering children.

Adult↗

Intratubular germ cell neoplasia of unclassified type occupying the whole testis accompanied by a small mature teratoma and metastatic choriocarcinoma and Sertoli cell-only tubules in the other testis.

A 19-year-old man with mild mental retardation was diagnosed as having metastatic choriocarcinoma and a testicular tumor. Histopathological examination of the resected testis revealed the presence of a small lesion of mature teratoma but no trace of choriocarcinoma. The remaining seminiferous tubules were atrophic and lined by large atypical germ cells, which were diagnosed as intratubular germ cell neoplasia of the unclassified type (IGCNU). A small area with prominent tubules was also observed. Within this lesion, the tubules were dilated and contained several layers of cells with central necrosis. Immunohistological comparison of staining for several biological markers (Ki-67, c-kit and placental alkaline phosphatase) between cells in the atrophic tubules and those in the dilated tubules indicated a progression of the latter cells to cells with a more proliferative ability. In the opposite testis, examined at autopsy after death due to metastatic choriocarcinoma, all seminiferous tubules were lined by Sertoli cells only. It was therefore assumed that the germ cell tumor of the combined histological type had primarily arisen in the background of IGCNU, and that choriocarcinoma had spontaneously regressed. The early onset of these testicular neoplastic lesions strongly indicates their occurrence under the genetic background of gonadal dysplasia, the Sertoli cell-only syndrome. The possible relation of gonadal disease to mental retardation in this patient is also discussed.

Adult↗

Carcinoma in situ of the testis followed by an overt malignant teratoma of the testis within 12 months.

A case of bilateral metachronous testicular non-seminomatous germ cell tumour (NSGCT) is presented. The second tumour was preceded by carcinoma in situ, diagnosed at the time of the first orchidectomy. The patient was placed under active surveillance and 1 year later the second testis tumour developed. A second orchidectomy was performed and testosterone replacement begun. Carcinoma in situ of the testis is discussed.

Adult↗

[Should the contralateral testis be systematically biopsied after orchidectomy for unilateral germ cell tumour of the testis?].

Intratubular neoplasia (ITN) of the testis is a precursor of germ cell tumour, apart from spermatocytic seminoma. It is often detected in testicular tissue adjacent to germ cell tumours, but is less common in the contralateral testis. Early diagnosis of ITN by testicular biopsy would allow earlier, conservative management. However, this approach remains highly controversial except in very specific indications.

Biopsy↗

Testis tumor: the problem of the undescended testis.

The increased incidence of testicular cancer occurring in the undescended testis is well documented. Ten to 12% of cryptorchid testes are demonstrated in all series of testicular cancer which is in keeping with a 4 to 10 times increase of the risk. A lot of work is being carried out to elucidate the etiological factors that could explain this increase. A common etiological endocrine factor might be implicated. As it is well known that orchidopexy does not prevent subsequent malignancy, its effects on the histology of the testis and tumor pattern is studied with consideration of age at orchidopexy. Carcinoma in situ (Cis) first discovered in the infertile male population and seen many years before invasive cancer may provide a useful tool for follow-up of cryptorchid patients. According to the results of this work, management of cryptorchid testes is planned as either orchidopexy or orchidectomy, and time and place for biopsies is decided. Life-long follow-up is advocated.

Adult↗

Testis-sparing surgery for benign lesions of the prepubertal testis.

Testis tumors in children are more likely to be benign that those in adults, and those tumors that are malignant are associated with a much lower incidence of metastases. As a result, a less-aggressive surgical approach to pediatric lesions has evolved. A testis-sparing operation in appropriate cases has potential psychological and cosmetic advantages for the developing child, and there may be functional advantages for fertility when the child matures.

Child↗

On the morphology of the transitional zones from the rete testis into the ductuli efferentes and from the ductuli efferentes into the ductus epididymidis. Investigations on the human testis and epididymis.

Transitions from the rete testis into the ductuli efferentes and from the ductuli efferentes into the ductus epididymidis were examined in the epididymes of 4 patients with prostatic cancer aged 65, 72, 77 and 78 years, in the epididymis of a 19 year-old accident victim and in the epididymis of an embryo of the 12th week. Concerning the former area, the results published up to now were confirmed. But according to our examinations, the transition from the ductuli efferentes into the ductus epididymidis is different from what has been described in the literature so far. In the adult human, the ductuli efferentes do not show end-to-side connections with the ductus epididymidis, but end-to-end junctions with "extensions" of the ductus epididymidis which finally join the ductus epididymidis end-to-side. However, in the epididymis of the embryo, one still finds end-to-side connections of ductuli efferentes and the ductus epididymidis. It was concluded that the extensions of the ductus epididymidis are formed during the development of the system of canaliculi in the epididymis from the embryonal stage to adult age.

Adult↗

Testis-specific histone H1t is truly a testis-specific variant and not a meiotic-specific variant.

Immunoblotting studies using highly specific polyclonal anti-histone H1t-IgG, which was extensively characterized by us previously, did not produce a signal with any of the histone H1 subtypes of either 1-day-old or adult rat ovarian nuclei. The absence of histone H1t in ovarian nuclei was also confirmed by indirect immunofluorescence studies. It is concluded, therefore, that histone H1t is truly a testis-specific histone variant and not a meiotic-specific variant.

Animals↗