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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↗

Localization of transforming growth factor beta 1 and beta 2 during testicular development in the rat.

The transforming growth factor beta s (TGF beta s) affect the metabolic activities of the somatic cells of the testis. Sertoli cells, peritubular/myoid cells, and germ cells contain mRNA for TGF beta 1 and/or TGF beta 2. We have used immunohistochemical techniques to determine, in vivo, when TGF beta 1 and TGF beta 2 are present in the rat testis during development and have identified the precise localization of these growth factors. The most pronounced changes in TGF beta immunoreactivity occurred during spermatogenesis. TGF beta 1 predominated in spermatocytes and early round spermatids, but as the spermatids elongated around stages VIII-IX of the cycle, the TGF beta 1 levels declined. TGF beta 2 was undetectable in spermatocytes and early round spermatids, but as spermiogenesis progressed, around stages V-VI, the spermatids rapidly acquired TGF beta 2. The intense staining for TGF beta 2 was maintained as the spermatids elongated. TGF beta 1 immunoreactivity was detected in Sertoli cells throughout testicular development. TGF beta 2 was found in fetal Sertoli cells, but became undetectable rapidly after birth. In fetal animals the Leydig cells contained TGF beta 1 and TGF beta 2; after birth TGF beta 1 persisted whereas TGF beta 2 became undetectable in the Leydig cells. Prior to puberty, TGF beta 1 and TGF beta 2 were absent in a portion of the Leydig cells; when the adult stage was reached, TGF beta 1 was no longer detectable and TGF beta 2 staining was faint to absent. In conclusion, our novel findings show that TGF beta 1 and TGF beta 2 are present in vivo in testicular cells at clearly defined stages of their differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Gonadal dimorphism explained as a dosage effect of a locus on the sex chromosomes, the gonad-differentiation locus (GDL).

In human somatic cells bearing two X chromosomes, one X is genetically inactivated throughout most of its length, whereas in cells with one X and one Y both sex chromosomes are active (with the exception of the constitutive heterochromatin of the Y that is inert). The vast base of information concerning normal and abnormal human sexual development that has accumulated since the advent of human cytogenetics 3 decades ago can be integrated by the following hypothesis: Homologous gonad-differentiation loci (GDLs) exist on the X and Y. The GDLs are strictly sex-linked; that is, normally they do not recombine during spermatogenesis, so that considerable divergence in DNA sequence doubtless has occurred between the locus on the X and the locus on the Y. The abundance of their evolutionarily conserved product--a substance still to be identified--determines the path of differentiation that the indifferent gonadal anlage of the early embryo will take: if only one GDL is transcribed, the case when two X chromosomes are present, ovary will develop; if two GDLs are transcribed, the case when a Y is present along with an X, testis will develop. By implication, facultative X inactivation is an integral and essential component of the system adopted in mammalian evolution for accomplishing gonadal--viz., sexual--dimorphism.

Chromosome Mapping↗

Differential distribution of the alpha 6 subunit of integrins in the development and sexual differentiation of the mouse testis.

The distribution of the alpha 6 subunit of integrins in the development and sexual differentiation of mouse testis was analyzed by light and electron microscopy during the embryonic, fetal and early postnatal periods. At the pregonadal phase only the epithelial cells of the mesonephric duct and of the distal mesonephric tubules showed a reaction to alpha 6, whereas the surface epithelium and the mesenchyme of the mesonephros were negative or contained only a rudimentary amount of the alpha 6 subunit. With the formation of the gonadal ridge and the testicular blastema, the gonadal cells became positive for the alpha 6 subunit. This expression remained in embryonic cord cells and in the vascular endothelial cells, whereas the differentiating cells of the surface epithelium, tunica albuginea, the Leydig cells, and the interstitial mesenchymal cells were negative. With the fetal and postnatal differentiation, the expression of the alpha 6 subunit gradually diminished in the cord cells, and by the prepubertal phase, alpha 6 was found only at adhesion sites between some Sertoli cells. Similar changes were seen in the mesonephric duct and tubules, and in the rete cords. The presence of alpha 6 in regions undergoing developmental cell aggregation processes and their disappearance during tissue maturation, suggest that alpha 6 plays a specific but transient role in gonadal cell adhesion necessary for the histogenetic organization of the testis. In addition to its role in developing and organizing cells, alpha 6 integrin was also a prominent component in degenerating cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Arteriographic diagnosis of a tumor arising from an undescended testis].

A case with a tumor developed in an undescended testis diagnosed by arteriography is shown. Radiological diagnostic procedures in the diagnosis of cryptorchism are discussed. It is established that selective testicular arteriography is of great value in the preoperative diagnosis of an intra-abdominally located tumor developed in an undescended testis even in the area of modern high resolution non invasive imaging modalities.

Adult↗

Metastatic testicular choriocarcinoma of the skin. Report and review of the literature.

Choriocarcinoma is a malignant growth of trophoblastic cells characterized by secretion of human chorionic gonadotropin. Choriocarcinoma usually arises from fetal trophoblasts and rarely arises from germ cells in the testis or ovary or derives from dedifferentiation of other carcinomas. Skin metastasis of choriocarcinoma is rare: only seven cases have been reported in the English and Japanese literature. We report the case of a 22-year-old Japanese man with pure choriocarcinoma of the testis who developed skin metastases that presented as multiple reddish nodules. Microscopic examination of both the primary lesion of the testis and the cutaneous metastasis demonstrated the typical histologic features of pure choriocarcinoma. The patient died 3 months after the initial onset of skin metastasis. Review of the literature indicates that skin metastasis of choriocarcinoma usually occurs as a nodular lesion with the histologically typical feature of the primary disease and signals of poor prognosis.

Adult↗

[Effect of zinc deficiency on apoptosis of spermatogenic cells of rat tostis].

OBJECTIVE: To study the changes of testis apoptosis in zinc deficient rats will promote the understanding of the molecular mechanism of zinc deficiency in the development and function of testis. METHODS: 16 Wistar rats were divided randomly into zinc control group (ZC) and zinc deficiency group (ZD). The serum and testis zinc contents were measured with atomic absorse method; the apoptosis of spermatogenic cells was studied with in situ nick translation (ISNT) technique. RESULTS: Under zinc deficient status, the zinc contents of the serum and testis were obviously decreased (P < 0.05). The apoptosis number of spermatogenic cells was significantly increased (P < 0.01). CONCLUSION: The adequate amount of zinc is essential to the development of testis, whereas zinc deficiency can harmfully affect it. This effect is perhaps carried out in different ways, but the increasing apoptosis numbers of spermatogenic cells might be one of molecular miechanisms of the effect of zinc defficiency on testis development.

Animals↗

Transgenic mice demonstrate a testis-specific promoter for angiotensin-converting enzyme.

There are two isozymes of angiotensin-converting enzyme (ACE), one produced by somatic tissues and a smaller protein synthesized by developing spermatozoa (testis ACE). To investigate the molecular control of testis ACE, we generated mice transgenic for a construct containing a putative testis-specific ACE promoter linked to the Escherichia coli reporter gene encoding beta-galactosidase. The transgenic mice express beta-galactosidase protein and RNA only within the testis. Histochemical analysis of the transgenic mice shows co-localization of beta-galactosidase protein and endogenous ACE within elongating spermatozoa. These studies demonstrate that transcription of testis ACE is controlled by a strong intragenic testis-specific promoter that is contained within a 698-base pair fragment immediately upstream from the transcription start site of testis ACE. Characterization of the testis ACE promoter may provide insights into the molecular mechanisms controlling cell stage-specific gene expression in the male germ line.

Animals↗

[Isolation and identification of spermatids from mouse testis].

OBJECTIVES: To develop a simple and effective method by which spermatids can be isolated from mouse testis. METHODS: Combination of enzymatic digestion was used to prepare suspension of spermatogenic cells from adult mouse testis, and then a modified discontinuous Percoll gradient (15%, 22%, 30%, 40%, 50%, 60%) centrifugation method was introduced to isolate spermatids from the cellular suspension. The content of spermatids in each isolated fraction by Percoll method was determined by morphology (Wright-Giemsa staining) and flow cytometry analysis, and the viability of spermatogenic cells was assessed using Eosin Y exclusion test. RESULTS: More than 97% of the testicular cells remained their viability after enzymatic digestion. After Percoll centrifuged, six fractions were formed. In each isolated fraction, the 22% fraction contained mostly spermatids(mean 86.7%) and cell viability was more than 85.5%. While in the 30% fraction, immature spermatogenic cells were present, and more than 92% of the cells remained their viability. CONCLUSIONS: A large of relatively purified spermatids can be isolated from mouse testis by enzymatic digestion combined discontinuous Percoll gradient centrifugation method.

Animals↗

Specific expression of the mRNA for 25 kDA heat-shock protein in the spermatocytes of mouse seminiferous tubules.

The 25 kDa heat-shock protein (Hsp25) is a member of the family of small heat-shock proteins. We investigated the expression and cellular localization of Hsp25 mRNA in the testis of adult and developing mice using Northern blotting and in situ hybridization techniques. In the early postnatal days, i.e., before the onset of spermatogenesis, no Hsp25 mRNA was detected in the testis. At around 10 days postpartum, Hsp25 mRNA began to be expressed in the testis in coincidence with the onset of the first wave of spermatogenesis and increased in amount progressively toward adulthood. Throughout the testis development, the signal for Hsp25 mRNA was localized exclusively to germ cells and was not detected in Sertoli or interstitial cells. The testis of W/Wv mutant mice, which lack the germ cell line, exhibited no Hsp25 mRNA expression. In the testis of normal adult mice, the abundance of Hsp25 mRNA differed among the seminiferous tubules in different stages of spermatogenesis. The most intense signal for Hsp25 mRNA was localized to the spermatocytes at leptotene, zygotene and early pachytene phases, which are present in the tubules of stages I-III and IX-XII. The signal decreased in intensity in the late pachytene and diplotene spermatocytes and was not detected in spermatids. Spermatogonia were also devoid of the signal. These results suggested that Hsp25 plays some specific role in the meiotic prophase of the testicular germ cell.

Animals↗

Quantitation of testicular and somatic cytochromes c in testis and somatic tissues from developing rats.

By combining chromatographic and spectral procedures, simple and quantitative assays for somatic cytochrome c (cyt cs) and testicular cytochrome c (cyt ct) in crude animal tissue extracts were developed. Using this assay procedure, limited developmental studies of cyt ct and cs were performed with tissue extracts of 27-, 58-, and 85-day-old rats. Specific contents of cyt cs in somatic tissues (i.e., micrograms of cyt c/g of tissue) of these three age groups did not show significant variations. However, the amounts of both cyt ct and cs in testis were markedly increased as the rats approached maturity. Increasing cyt ct/cyt cs ratios as the rat developed to maturity suggest that expression of cyt ct is preferentially required for specific function of testis. Application of both molecular biological techniques and this assay (for holo-cyt ct) should be useful to study the overall regulation of the expression of cyt ct in testis.

Aging↗

Development of the human fetal testis.

We describe the histological features of the fetal testis, utilizing 68 fetuses ranging in gestational age from 10 to 41 weeks. During fetal life, the tunica albuginea progressively increases in thickness, and between 29 and 32 weeks it develops two layers. Beyond 25 to 28 weeks, septa are invariably present. Tubules begin as straight structures and become maximally coiled by 30 weeks. Tubular diameter reaches its maximum by 16 weeks and remains constant throughout the rest of gestation. Germ cell and Sertoli cell numbers per tubular diameter have a wide range, but the median number for each cell type remains constant after 13 to 16 weeks. Leydig cells are most numerous between 17 and 19 weeks and decline thereafter. They are infrequent but still present at term. Interstitial lipochrome pigment accumulates during the latter half of gestation and may represent breakdown products from Leydig cell degeneration.

Embryonic and Fetal Development↗

Androgen binding protein as a biochemical marker of formation of the blood-testis barrier.

Androgen binding protein (ABP) was measured during postnatal development in normal and irradiated rats to determine whether development of a blood-testis barrier and formation of a continuous lumen from testis to epididymis is correlated with entry of ABP into the caput epididymis. ABP is found in normal testis as early as 14 days postnatally (0.2 pmol/mg), at which time no blood-testis barrier is observed by the peroxidase perfusion technique. Previous findings have shown a close correlation of blood-testis barrier development and lumen formation. Indeed, ABP is not detectable in the epididymis until 18-20 days of age (1.0 pmol/mg) at which time blood-testis barrier formation and lumen development is complete. Whole body irradiation (125 rads) of pregnant rats at 19-20 days of gestation produces male offspring with seminiferous tubules remarkably free of germinal epithelium and containing essentially only Sertoli cells. These Sertoli cell-enriched (SCE) testes produce normal amounts of ABP between 14 and 21 days postnatally. However, between 21 and 30 days of age the specific activity of ABP is significantly higher in the SCE tests (2.8 pmol/mg protein) than in normal testis (0.5 pmol/mg protein). In the SCE testis neither blood-testis barrier development nor lumen formation are complete until 30 days of age, at which time ABP is first detectable in epididymis of the irradiated rat. Thereafter there is a gradual decline of ABP in the SCE testis-and a dramatic increase in the epididymis. NIH-FSH-S-10 (200 mug/rat) injected SC into 14-day-old normal rats stimulated ABP in the testis from control levels of 0.15 pmol/mg to 1.46 pmol/mg within 4 h after injection. However, no ABP was detectable in the epididymis of either the control or the FSH-stimulated rats. These findings suggest that entry of ABP into caput epididymis is an index of blood-testis barrier formation and lumen development.

Androgens↗

The influence of neonatal orchiopexy upon the testis in persistent Müllerian duct syndrome.

We report on a patient with persistent müllerian duct syndrome and normal external genitalia who had embryonal cancer of the testis 16 years after neonatal bilateral orchiopexy. In previous cases the testes of these patients have not been considered predisposed to form tumors. However, the occurrence of a testis tumor has been reported in 8 patients with this syndrome. The specific factors resulting in tumor formation in such patients are uncertain. Until they are clarified we suggest that these patients should be observed carefully for the possible development of testis tumor.

Adolescent↗

Isolation and partial characterization of basic fibroblast growth factor from bovine testis.

A basic fibroblast growth factor (FGF) has been purified to homogeneity from bovine testis, using ammonium sulfate precipitation of the crude extract followed by three chromatographic steps, involving cation-exchange, heparin-Sepharose, and reversed-phase HPLC. Gas-phase sequence analysis showed the amino-terminal amino acid sequence of the isolated polypeptide as His-Phe-Lys-Asp-Pro-Lys-Arg-Leu-Tyr-, which is identical to the amino-terminal of the (16-146) fragment of basic FGF previously characterized from corpus luteum, adrenal, and kidney. The purified FGF was shown to have the same biological activity as that of basic FGF (1-146). This finding suggests that basic FGF is present in testis and may act as a local regulator of testicular function. In addition, testicular FGF might play an important role in spermatogenesis and/or the development of testis.

Amino Acid Sequence↗

Testicular cancer.

Despite the overall cure rate now in excess of 90%, innovation in management of germ cell tumors continues. The report that 80% of patients with extragonadal germ cell tumors have either carcinoma in situ or atrophic tubules as evidence of tumor rejection emphasizes the need to investigate the testis in patients with undiagnosed primary cancer because even today treatment delay is worsening prognosis. The evidence that testicular atrophy is a precursor of malignancy may explain why testis cancer has increased while normal sperm count has fallen over the past 50 years and why there is an association between exposure during service in Vietnam to agents that damage spermatogenesis and development of testis cancer. The improved prognostication from analysis of large databases and salvage with high-dose chemotherapy and bone marrow rescue are giving confidence to explore new innovations, eg, carboplatin instead of cisplatin. In addition, as the database on patients with stage I disease on surveillance enlarges, so does interest in adjuvant chemotherapy, encouraging the search for better markers to predict poor response. Linkage between overproduction of the tumor marker lactate dehydrogenase-1 and the increased copy number of the isochrome 12p in the tumor may be of use in this respect. Reports that germ cell tumor patients exposed to etoposide, eg, leukemic, lung, and ovarian cancer patients, can develop an acute myeloid leukemia with a marker on chromosome 11 are tempering enthusiasm for its use in adjuvant therapy. However, the observation that radiotherapy or chemotherapy may reduce second testis tumor incidence more effectively than surgery does encourages more detailed exploration of the results of adjuvant treatment.

Dysgerminoma↗

Suppressive effect of fetal testes on development of fetal ovaries transplanted into adult males in the rat.

The age-related testicular effect on the ovarian primordia was studied by combined transplantation of fetal testes and ovaries in adult male hosts. First, ovarian primordia of 14-day fetal rats were transplanted into a renal subcapsular position of castrated or intact adult male rats. In both the castrated and the intact hosts, most of the ovarian transplants developed normally with only 3 of them having in part seminiferous tubule-like structures in addition to normal ovarian structure. Second, a 14-day ovary was combined with a fetal testis the age of which varied from 13- to 18-day, and the combination was transplanted. In the combination of a 14-day ovary and a 13-day testis, the results varied in such a way that the ovary or the testis alone developed or otherwise, both gonads developed well. In union with 15- to 18-day testes, the ovaries did not develop, although the testes developed well. These results suggest that the 14-day ovarian primordia have a slight reactiveness to androgens of host rats and that the 13-day fetal testes begin to inhibit the development of the 14-day ovaries co-transplanted with them.

Animals↗