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Gonadotrophin-induced changes in the Sertoli cells of the immature mouse testis.

Highly purified preparations of human pituitary gonadotrophins were administered to immature male mice daily for 3 days. The mice were killed on the 9th day after birth and the testes were prepared for electron microscopy. FSH treatment caused an increase in the mass of Sertoli cell cytoplasm, and FSH and LH increased the size of mitochondria in these cells. The number of polysomes in each Sertoli cell was increased after FSH treatment, but the number of ribosomes/polysome was not affected.

Animals↗

Developmental patterns of enzymes in mouse testis.

Study of the activities of hyaluronidase, lactate dehydrogenase isoenzyme-X and the dehydrogenases of sorbitol, alpha-glycerophosphate, glucose-6-phosphate, malate, glyceraldehyde-3-phosphate and isocitrate in the testes of mice of different ages showed that the changes were correlated with the stages of spermatogenic cell differentiation. The first 4 enzymes had activities which were low in newborn mice and high in adults; this pattern was reversed for the other enzymes.

Age Factors↗

Binding of 125I-labelled FSH in the mouse testis in vitro.

In-vivo testicular binding of highly purified pituitary FSH, labelled by a method which did not significantly affect biological potency, was hormone-specific, tissue-specific and dose-dependent. Hypophysectomy of mice was followed by a progressive increase in the amount of 125I-labelled FSH per unit weight of testis but not in the total amount of hormone taken up by the testis. Maximum binding occurred at 4 h in a membrane-containing fraction prepared by high-speed ultracentrifugation of testicular homogenate. This is considerably later than has been reported for testicular tissue incubated in vitro at 37 degrees C.

Animals↗

Autoradiographic study of lysine and arginine incorporation stimulated by follicle-stimulating hormone in the mouse testis in vivo.

Hypophysectomized adult mice were given injections of highly purified FSH 12 h before killing, and of tritiated lysine or arginine 2 h before killing. Autoradiographs were prepared from paraffin wax sections of testes. Treatment with FSH increased the density of silver grains over the nuclei of the Sertoli cells and of all types of germinal cell except the early spermatids. The stimulatory effect of GSH on incorporation of both lysine and arginine was most marked in the nuclei of preleptotene primary spermatocytes. The ratio of arginine to lysine incorporation was greater in spermatids undergoing nuclear elongation than in other types of cell.

Animals↗

Timing and localization of the stimulatory effect of follicle-stimulating hormone on uridine incorporation in the mouse testis in vivo.

Human pituitary FSH increased the incorporation of [5-(3)H]uridine into RNA in vivo in the testes of intact 9-day-old mice and of hypophysectomized adults. In both groups the effect was greatest 8 h after administration of 5--7.5 i.u. FSH. Autoradiographs were prepared from the testes of hypophysectomized adult mice given subcutaneous injections of FSH or of 0.9% saline 6 h, and [5-(3)H]uridine 1.5 h, before death. Treatment with FSH caused statistically significant increases in the density of silver grains over the nuclei of Sertoli cells, type A and intermediate spermatogonia, and preleptotene and mid-pachytene primary spermatocytes. It was concluded that FSH has a generalized stimulatory action on RNA synthesis in the nuclei of Sertoli cells and those types of germinal cell which synthesize RNA most actively.

Animals↗

Expression and functional role of hepatocyte growth factor and its receptor (c-met) during fetal mouse testis development.

The hepatocyte growth factor (HGF) is a pleiotropic cytokine able to regulate different cellular functions. HGF action is mediated by its receptor, c-met, a glycoprotein with tyrosine kinase activity. We previously demonstrated that c-met is expressed in the newly formed seminiferous cords of the mice embryonic testes and that HGF acts as a morphogenetic factor. In this paper, we report that at 15.5 days post-coitum (dpc) c-met is expressed in the testicular cords, whereas at 18.5 dpc c-met expression is almost exclusively localized in the interstitial tissue of the testis in particular in the fetal Leydig cells. In addition, we demonstrate that HGF gene is expressed during the fetal period of testis development, heavily detectable in the interstitial compartment of 18.5 dpc testes. Interestingly, HGF is not expressed in the Leydig cells that, as above reported, express the HGF receptor. Looking for the functional role of HGF on Leydig cells, we evaluated the amount of testosterone secreted by testes isolated from 18.5 dpc embryos and cultured in the presence of HGF. The results of the in vitro organ culture show that, at this age, HGF increases the amount of testosterone secreted in the culture medium. On the contrary, HGF does not modulate the amount of testosterone secreted by testes isolated from 15.5 dpc embryos. In conclusion, we report that HGF is produced in the interstitial compartment of the developing testis but not by the Leydig cells. Conversely, the HGF receptor c-met is expressed in the Leydig cells and HGF modulates Leydig cell function during the late period of prenatal development.

3-Hydroxysteroid Dehydrogenases↗

Age-related histologic changes in the adult mouse testis.

Age-related changes in the testis were studied histologically in dd-mice from 2 months to 2 years of age. After 6 months of age, vacuoles appeared first singly and later became clustered in the seminiferous epithelium. With the appearance of the vacuoles, the epithelium started to release spermatids and spermatocytes into the lumen. Multinucleated giant cells occasionally appeared in the epithelium and were also released to the lumen. The epithelium, when markedly depleted of germ cells, was composed mainly of Sertoli cells. The lumen of the atrophied tubules occasionally contained accumulations of macrophages, sperm aggregations, and nodules of a homogeneous material covered with flattened epithelial cells. The basement membrane surrounding the atrophied tubules thickened corresponding to the degree of atrophy. The atrophied tubules initially appeared in patches and then spread throughout the testis. Leydig cells increased in amounts with age. The increase of Leydig cells was distinct around severely atrophied tubules with a thickened basement membrane. These changes are discussed in comparison with autoimmunized testes which show similar histologic changes.

Aging↗

Estrogen agonists, 17beta-estradiol, bisphenol A, and diethylstilbestrol, decrease cortactin expression in the mouse testis.

Previous reports have revealed that estrogen agonists or anti-androgenic chemicals induce abnormal spermiogenesis in rodents. In the seminiferous epithelium, the apical ectoplasmic specialization (ES) is an actin-based (cell-cell) junctional structure developing between the Sertoli cells and spermatids as is the basal ES also--although it is located between adjoining Sertoli cells. In the apical and basal ES are several adhesion complex proteins that control the spermatid developing process. Cortactin, an actin-binding protein, is one of the ES adhesion proteins, combining with several cell-cell adhesions associating proteins. In the present study, 17beta-estradiol (E2, 1.2 microg/kg), bisphenol A (BPA, 2.4 microg/kg), and diethylstilbestrol (DES, 2.5 microg/kg) were subcutaneously injected in ICR 12-week-old male mice. Mice testes were observed for the expression of cortactin protein after E2, BPA, and DES treatments by Western blot analysis, immunohistochemical analysis, and immunoelectron microscopic analysis. Observations showed that the immunoreactivity of the treated testes was significantly decreased. The immunohistochemical reactivity of cortactin in the apical ES was decreased in the treated testis. In immunoelectron microscopic observations, ultrastructural immunolocalizations of cortactin protein in the apical ES by both E2 and BPA were decreased, and the immuno-gold particles of apical and basal ES by DES were much less than the control. In the toxicological field, cortactin may be considered to be one of the indicator proteins of abnormal spermiogenesis which is affected by exogenous chemicals, such as endocrine disrupting chemicals. In summary, this study helps toward understanding the cortactin protein expression underlying the histological abnormalities of spermatogenesis induced by exogenous hormonal chemical treatment.

Animals↗

Development of mouse testis and epididymis following intrauterine exposure to a static magnetic field.

In order to test if the in utero exposure to static magnetic fields affects testis and epididymis development in mice, females were exposed to 0.5-0.7 T, generated by a permanent magnet, from day 7 of gestation to the day of birth. No significant differences were found between exposed and sham-exposed animals with respect to body weight gain of dam during the gestational period, litter size, body weight of male pups at the day of birth, and body or testis-epididymis weight gain of pups from birth to day 35. Histopathologic evaluation of testis and epididymis of pups of 1, 5, 15, and 35 days of age showed no detectable alterations due to in utero exposure to static magnetic fields.

Aging↗

Histologic changes in the mouse testis after bilateral vasectomy.

AIM: To study the effect of vasectomy on histological appearance of the testis. METHODS: Parkes strain mice were used as the animal model; they were bilaterally vasectomized (Vx) or sham-operated (So) and killed at intervals of 4, 6, 9, and 12 months after the operation. Testes were excised from 5 Vx and 5 So mice at each interval and processed for histological examination. RESULTS: Testes of So mice showed normal histological features. By contrast, marked alterations were observed in the seminiferous tubules in testes of Vx mice, except in those killed 4 months after the operation. The seminiferous epithelium in the tubules was only 2-3 layers thick and showed much depletion of germ cells; in severe cases, the epithelium consisted of only a thin layer of Sertoli cells, spermatogonia and a few spermatocytes. Exfoliation of germ cells, occurrence of multinucleated giant cells and vacuolated appearance of the epithelium were of common features in the tubules. Furthermore, lumen of the rete testis in Vx mice was greatly dilated and showed accumulation of spermatozoa with immature germ cells; in mice vasectomized for 6-12 months, several macrophages ingesting spermatozoa were often observed in the lumen of the rete testis. Spermatic granuloma was also sometimes noticed in corpus or in cauda regions of the epididymis in mice vasectomized for 6-12 months. CONCLUSION: We suggest that consequences of vasectomy should be thoroughly understood in order to make this method rather more popular as a reversible method of male contraception.

Animals↗

Promotion of seminomatous tumors by targeted overexpression of glial cell line-derived neurotrophic factor in mouse testis.

We show with transgenic mice that targeted overexpression of glial cell line-derived neurotrophic factor (GDNF) in undifferentiated spermatogonia promotes malignant testicular tumors, which express germ-cell markers. The tumors are invasive and contain aneuploid cells, but no distant metastases have been found. By several histological, molecular, and histochemical characteristics, the GDNF-induced tumors mimic classic seminomas in men, representing a useful experimental model for testicular germ-cell tumors. The data also show that a deregulated stimulation of a normal proto-oncogene by its ligand can be an initiative event in carcinogenesis.

Aneuploidy↗