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Differential expression of placental (P)-cadherin in sertoli cells and peritubular myoid cells during postnatal development of the mouse testis.

BACKGROUND: In previous work, RNA transcripts for placental (P)-cadherin, a calcium-dependent cell adhesion molecule, were identified in the rat testis during the first 4 weeks of postnatal development. However, the cells in the testis responsible for P-cadherin expression have not yet been identified. METHODS: We used conventional epifluorescence microscopy to examine P-cadherin immunoreactivity in cryostat sections of mouse testis and scanning laser confocal microscopy to localize P-cadherin and beta-catenin in wholemount preparations of mouse seminiferous tubules. We used fluorescent phalloidin to identify actin filaments. RESULTS: Sertoli cells expressed P-cadherin on postnatal days 1, 3, and 8, but not on any day thereafter. In contrast, peritubular cells did not express P-cadherin on postnatal day 8 and continued expression in adulthood. beta-Catenin was localized near contact areas between peritubular cells on postnatal days 12 and 15. A mature pattern of actin filament organization in peritubular cells appeared on day 15 and coincided with the uniform appearance of P-cadherin and beta-catenin near areas of contact between adjacent peritubular cells. CONCLUSIONS: During postnatal development of the testis, the earlier expression of P-cadherin by Sertoli cells is replaced by the subsequent expression of P-cadherin by peritubular cells. The expression of P-cadherin in peritubular cells is correlated temporally with the expression of beta-catenin and the development of a mature network of actin filaments and is consistent with a role in intercellular adhesion and junction formation.

Aging↗

Primary carcinoid tumor of the testis: case report, ultrastructure and review of the literature.

A case of primary pure carcinoid tumor of the testis which occurred in a 71-year-old male is reported. The patient was treated by radical orchiectomy and remains well and symptom free 10 months after operation. Histologically as well as ultrastructurally the tumor showed typical appearances of carcinoid tumor of midgut derivation. 23 cases of carcinoid tumors of the testis were discovered in the literature. Of these 17 were primary testicular carcinoids, and 6 were metastatic to the testis. Of the 17 cases of primary carcinoid tumors, 14 were pure carcinoids and only 3 were associated with teratoma. None of the primary testicular carcinoids were associated with metastases and the prognosis after orchiectomy was excellent, thus indicating that no further therapy is necessary. The prognosis of patients with carcinoid metastatic to the testis is poor. In view of this it is very important to determine whether the tumor is primary or metastatic.

Aged↗

Undifferentiated intratubular germ cell tumor of the testis: light and electron microscopic study of a unique case.

A 34-year-old white man was found to have a nodule on the surface of right testis which turned out to be metastatic embryonal carcinoma within the tunica albuginea. Examination of the orchiectomy specimen revealed extensive undifferentiated intratubular germ cell tumor (carcinoma in situ) with foci of intratubular embryonal carcinoma and seminoma. Ultrastructure of the cells comprising the carcinoma in situ was similar to that of undifferentiated germ cells. The development of intratubular embryonal carcinoma and seminoma in a testis with extensive carcinoma in situ lends further support to the concept that carcinoma in situ or the testis represents an undifferentiated germ cell tumor from which other types of germ cell tumors of the testis may evolve.

Carcinoma in Situ↗

Epidermoid cysts of the testis: a report of three cases and an analysis of 141 cases from the world literature.

Epidermoid cysts of the testis are rare and represent about 1% of all testicular tumors. An analysis of 141 cases reported to date in the world literature, including the cases reported here, indicates that 50% of the lesions occur in the third decade and 86% between the second and fourth decade. The most common presentations are painless enlargement of the testis (41%) for an average period of 2.25 years or incidental detection during routine physical examination (33%). Clinically, a discrete testicular nodule can be palpated in the majority of the cases (76%). Pathologic findings are those of a squamous lined cyst containing keratin with absence of appendages or other elements. It is believed that, despite the benign nature of the lesion, they should be treated by orchiectomy so that a thorough pathologic examination can be done to establish a confident diagnosis. While some controversy exists about their source of origin, all the evidence, including the age, more common occurrence among whites, and the rare reported cases arising in cryptorchid testis points to a germ cell origin for these lesions. The epidermoid cyst should thus be recognized as another subtype in the category of germ cell tumors of the testis and perhaps the ovary.

Adult↗

Metastatic carcinoma involving the testis. Clinical and pathologic distinction from primary testicular neoplasms.

Metastatic carcinoma to the testis is unusual. There are only seven previously reported cases in which a testicular mass was the first clinical manifestation of an underlying malignancy. The authors review 127 cases in which the testis was involved by metastatic carcinoma, and describe an additional two patients in whom a malignant testicular mass was the presenting sign of an underlying nontesticular carcinoma. The tumors most commonly reported to metastasize to the testis are: prostate (45 cases), lung (25 cases), melanoma (12 cases), colon (11 cases), kidney (10 cases), stomach (6 cases), and pancreas (5 cases). Neuroblastoma, retinoblastoma, carcinoid tumor, and cancers of the bile duct, ureter, bladder, salivary gland, and thyroid have also involved the testis secondarily. Nineteen patients (15%) had bilateral testicular metastases. Patients with secondary testicular neoplasms were older in general than those with germ cell tumors (mean, 55 years; median, 57 years). Histologically, the presence of extensive lymphatic and vascular invasion and an interstitial pattern, in which the seminiferous tubules are spared, is suggestive of a metastasis. In four of the nine cases (44%) in which testicular enlargement was the first manifestation of an underlying carcinoma the correct pathologic diagnosis was initially missed. Serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) are occasionally elevated in patients with nontesticular primary tumors, but markedly elevated levels in young patients suggest a nonseminomatous germ cell tumor, as does positive immunoperoxidase staining for AFP and HCG.

Adolescent↗

27 kDa extracellular matrix protein revealed by a monoclonal antibody raised against rat testis.

In search of unique components of the seminiferous tubule extracellular matrix, monoclonal antibodies were raised against an isolated seminiferous tubule extracellular matrix, and the monoclonal antibody 12G11 was cloned. By immunofluorescence microscopy in eight kinds of rat tissues (testis, lung, liver, small intestine, cardiac muscle, skeletal muscle, kidney, and brain), 12G11 antigen existed only in the testis. Immunoelectron microscopy revealed that the antigen is localized in the basement membrane of the seminiferous tubule and in the basement membranes of myoid cells. For a biochemical analysis, eight kinds of rat extracellular matrices were isolated and solubilized with 8 M urea and 2% beta-mercaptoethanol. Immunoblot analysis of these samples in 0.8% agarose gel also showed that the antigen was specific for the testis, and in a two high-molecular weight aggregates. These aggregates seemed to contain type IV collagen and laminin chains. The antigen of 12G11 antibody was shown to be 27 kDa by 10% SDS-PAGE followed by immunoblotting. From these data, the existence of a testis specific 27 kDa basement membrane protein, which associate with type IV collagen and laminin, was suggested.

Animals↗

International patterns and trends in testis cancer incidence.

Although the incidence of testis cancer has risen markedly in many Western populations over the past half-century, it is not clear whether rates in other populations also have increased. To clarify this issue, we examined testis cancer incidence rates over the 25-year time period of 1973-1997 for selected populations around the world. Age-standardized incidence rates for 21 registries in the Americas, Asia, Europe and Oceania over successive 5-year time periods were obtained from volumes 4-8 of Cancer Incidence in Five Continents. Testis cancer rates rose between 1973 and 1997 in most populations worldwide, although the increases were strongest and most consistent among populations of European ancestry. Rates appear to be leveling off in some populations. The increases in testis cancer remain unexplained, although changes in the prevalence of important risk factors for this disease may be responsible.

Adolescent↗

Testis cancer: post-natal hormonal factors, sexual behaviour and fertility.

The relationship of risk of testis cancer, and subdivisions of the tumour by histology, to variables which may be related to hormonal status, sexual behaviour and fertility was investigated in data from a case-control study with 259 cases and 2 sets of controls. No consistent association was found between testis cancer risk and age at puberty, need to shave, obesity, alcohol intake, animal fat intake, and sexual behaviour. There was a significant excess of seminomas in very tall men. Testis cancer cases showed lower fertility than controls according to various measures, but this reflected the greater frequency of cryptorchidism among cases compared to controls. Among non-cryptorchid subjects there was no clear evidence that infertility was associated with risk of testis cancer.

Adolescent↗

Bilateral epidermoid cysts of the testis: sonographic and MRI findings.

Epidermoid cysts of the testis are rare benign lesions, without malignant potential, that can be managed conservatively with cyst enucleation and testis-sparing surgery. Bilateral epidermoid cysts in the testes have been reported very infrequently. We report the sonographic and MRI findings in a patient who presented with a palpable nodule in only 1 testis, but in whom sonography showed bilateral lesions. On sonography, the cysts had an internal "onion-ring" structure; color Doppler signals were absent. On MRI, the cysts had a laminated appearance, with alternating low- and high-signal-intensity areas on T2-weighted images. These imaging findings and the negative results of laboratory tests for tumor markers suggested the correct diagnosis, and testis-sparing surgery could be performed.

Adult↗

Sonographic appearance of isolated necrotizing vasculitis of the testis.

The presentation of necrotizing vasculitis of the testis is variable and may mimic a testicular tumor. Necrotizing vasculitis of the testis is characterized by fibrinoid necrosis of the walls of small and medium-sized testicular arteries. We report a patient with isolated necrotizing vasculitis of the testis who presented with clinical imaging findings suspicious for testicular neoplasm. We describe the clinical course and sonographic characteristics of evolving necrotizing vasculitis of the testis, briefly review the literature, and discuss the implications for the diagnosis and management of this condition.

Adult↗

Distribution of Sertoli cell microtubules, microtubule-dependent motors, and the Golgi apparatus before and after tight junction formation in developing rat testis.

Sertoli cells are polarized epithelial cells of the seminiferous epithelium which provide structural and physiological support for differentiating germ cells. They establish different basal and adluminal environments for the selective nurturing of pre- and post-meiotic germ cells within the seminiferous epithelium, segregated by the Sertoli-Sertoli cell tight junctional complex, the blood-testis barrier. Tight junction formation between epithelial cells in vitro is a critical polarizing event associated with changes in polarized targeting of membrane-specific proteins and reorganization of microtubules, centrioles, and the Golgi apparatus. To investigate whether tight junction formation is associated with organelle reorganization in Sertoli cells in vivo, we have characterized distribution patterns of Sertoli cell microtubules, the mechanoenzymes kinesin and cytoplasmic dynein, and the Golgi apparatus during tight junction formation in developing rat testis. Immunocytochemistry on samples taken at 5, 10, 15, 20, and 25 days of age was used to examine the distribution of these proteins during the extensive cellular reorganization that culminates in the formation of the blood-testis barrier at 19 days of age. Our data show that the distribution patterns reflect the extensive intercellular repositioning of tubule cells in developing seminiferous tubules, but that changes in intracellular organization are not temporally associated with formation of the blood-testis barrier.

Age Factors↗

Ameboid cells in spermatogenic cysts of caecilian testis.

Sertoli cells constitute a permanent feature of the testis lobules in caecilians irrespective of the functional state of the testis. The developing germ cells are intimately associated with the Sertoli cells, which are adherent to the basal lamina, until spermiation. There are irregularly shaped cells in the cores of the testis lobules that interact with germ cells at the face opposite to their attachment with Sertoli cells. These irregularly shaped (ameboid) cells first appear in the lumen of the cysts containing primary spermatocytes and are continually present until spermiation. We did not observe any cytoplasmic continuity between a Sertoli cell and an ameboid cell. Both light microscopic and TEM observations reveal a phagocytic role for the ameboid cells: they scavenge the residual bodies shed by spermatozoa. Organization of the ameboid cells is grossly different from that of the spermatogenic and Sertoli cells. They appear to develop from the epithelium at the juncture of the collecting ductule with the testis lobule.

Amphibians↗

Isolation and characterization of testis-specific cDNAs for luteinizing hormone beta-subunit in the rat.

To study further the unexpected expression of the luteinizing hormone (LH) beta-subunit in the rat testis, we identified in a rat testicular cDNA library three LH beta clones with lengths of 3.2, 2.4 and 0.86 kb (TLH beta 1, TLH beta 2 and TLH beta 3). The clones were identified using a 32P-labeled cDNA probe complimentary to the known rat pituitary LH beta mRNA. Clone TLH beta 2 corresponds in size to the main LH beta mRNA species (2.7 kb) detected by Northern hybridization in the rat testis. Sequence analysis indicated that the different sizes of the three clones are due to alternative RNA splicing and differences at the 5' ends of transcripts. The sequence of one open reading frame deduced from TLH beta 1 is almost identical with the pituitary LH beta peptide, differing only in three amino acids in the putative signal peptide. It might encode a functional testis-specific LH beta peptide. Shorter transcripts from clones TLH beta 2 and TLH beta 3 may correspond to short testicular LH beta peptides. The present findings provide further evidence in the rat for expression of testis-specific mRNA variants of the LH beta gene. Their translation products may form a novel class of testicular para/autocrine factors.

Alternative Splicing↗

Characterization of a novel zinc finger gene (ZNF165) mapping to 6p21 that is expressed specifically in testis.

Clone ZF388 was identified during the course of expressed sequence tag analysis of human adult testis cDNAs as being a member of the C2H2 zinc finger gene family. Northern blot analysis of a range of 16 different human tissues has shown that clone ZF388 detects a single 2.2-kb transcript and that the expression of this mRNA species is strictly specific to the testis. Sequence analysis of ZF388 and other clones isolated by rescreening a testis cDNA library has defined a transcript with an extensive N-terminal acidic domain containing 17% aspartic and glutamic acid residues and a C-terminal domain composed of five zinc finger motifs linked through the highly conserved sequence TGE-KPYE. This gene has been designated ZNF165. Analysis of somatic cell hybrids containing single human chromosomes shows that ZNF165 maps to chromosome 6. Fluorescence in situ hybridization of cDNA insert probes to male metaphase spreads shows that the ZNF165 transcript maps to 6p21 close to the human MHC region. Human 6p21 is homologous with the distal inversion of the mouse t-complex, which has been shown to contain a cluster of genes expressed specifically in the testis.

Adult↗

Interstitial cell carcinomas of the testis in Balb/C male mice ingesting methoxychlor.

Balb/c and C3H strains male and female mice ingested 750 ppm methoxychlor or 100 ppm DDT in the diet for 2 years. Balb/c strain male mice ingesting methoxychlor developed a highly significant incidence of interstitial cell carcinomas of the testis. Balb/c strain male mice ingesting DDT and C3H strain male mice receiving methoxychlor or DDT did not have testicular tumors. The carcinomas of the testis varied from well-differentiated to poorly differentiated and undifferentiated and were capable of metastasis. Carcinomas of the testis have been described in Balb/c strain male mice, but not C3H, given estrogens. The carcinogenicity for testis of Balb/c strain male mice is most likely related to the estrogenic activity of methoxychlor.

Animals↗

[Recurrent testicular torsion: is retorsion of a fixed testis possible? A case report and literature review].

Painful testicular torsion is an emergency which can occur at any age, even after previous fixation of the testis. In the described cases, it was not expected and a misdiagnosis led to loss of the testis. For a patient who has already lost one testicle, this is a catastrophe. A literature search was performed. Previous fixation of the testis does not always prevent torsion. The diagnostic work-up and management of acute testicular pain should not be different after previous fixation of the testis, regardless of age.

Adult↗

Results of orchiopexy for the undescended testis.

The undescended testis is one of the most common congenital abnormalities of the genitourinary system. Outcomes of orchiopexy include (1) having a viable, palpable testis in the scrotum, (2) fertility, as measured by paternity rates or semen analysis in adulthood and (3) risk of testicular cancer. Multiple operative techniques have been described and are associated with various success rates. In the past decade, success of orchiopexy for inguinal testes has been >95%. For abdominal testes, success for orchiopexy has been >85-90% in most series with single stage orchiopexy or two stage Fowler-Stephens orchiopexy, both with open surgical or laparoscopic technique. However, having a palpable testis in the scrotum does not assure fertility, as there are iatrogenic factors that may adversely affect the outcome. In adult men with a history of unilateral orchiopexy, fertility is nearly normal, but is significantly reduced following bilateral orchiopexy. The risk of testicular carcinoma is increased by a factor of 3.7 to 7.5 times. Tumor type is most commonly seminoma if the testis is undescended, whereas tumors that occur following orchiopexy are much more likely to be nonseminomatous.

Adult↗

Hyperacetylation of histone H4 in rat testis spermatids.

Acetate was incorporated efficiently into rat testis histones after an intratesticular injection of [3H]acetate. The pattern of in vivo acetylation of the testis histones was quite similar to the pattern of in vitro acetylation seen in a previous study with histones H3 and H4 acetylated to the greatest extent [13]. Acetylation of one or more of the major testis H2A variants was confirmed by analysis of these histones on high resolution polyacrylamide gels (PAGE) containing Triton X-100. Of the four variants, H2A.1 appeared to be labeled to the greatest extent. When testis cells were separated into highly enriched populations of specific cell types by centrifugal elutriation after an intratesticular injection of labeled acetate, histone H4 from all fractions of cells was acetylated, but histone H4 from the fraction of cells most enriched in elongating spermatids was hyperacetylated. Thus, the in vivo hyperacetylation of histone H4 which occurs in elongating spermatids is a physiological event which occurs during the relatively short time period when the entire complement of histones is replaced by more basic, protamine-like proteins, and therefore must be one of the key steps in this dramatic protein transition.

Acetates↗