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PubMed1982

Tritium toxicity in mouse testis: effect of continuous exposure during pre- and postnatal development.

Pregnant mice were continuously irradiated (5 micro Ci/ml of drinking HTO; 0.9 rd/day) from the 16th day post coitum. Quantitative and qualitative studies were made on testis of mice 3, 4 and 5 weeks post partum. Testes showed various histopathological lesions like cytoplasmic vacuolation, exfoliation, giant cell formation, denudation, haemorrhage, hyperaemia and sclerosis. Three weeks old mouse testis was found histopathologically more damaged. The population of spermatogonia types A, intermediate and B were maintained at approximately 80%, 70% and 60% of the controls respectively; while that of spermatocytes was maintained at roughly 70%. The population of spermatids at 4 and 5 weeks was approximately 45%.

Animals↗
PubMedDate not supplied

Multiple primary neoplasms in patients with testicular germ cell tumor.

The study of multiple primary neoplasms may provide more insight into the pathogenesis of specific cancers and, secondly, it addresses the issue of treatment-related induction of second tumors. 584 consecutive patients with testicular germ cell tumors treated during 1969-1992 in Berlin were retrospectively analyzed for the prevalence of multiple primary neoplasms. 23 patients (16 pure seminoma, 7 nonseminoma) developing nontesticular malignancies in addition to testis cancer were identified (3.9%, 95 confidence intervals +/- 1.6%). The mean age at the time of the testis cancer was 42.8 years, and mean age at the time of nontesticular malignancy was 50.2 years. In 4 cases, the nontesticular malignancy preceded testis cancer, in 3 patients both neoplasms occurred simultaneously, and in 16, nontesticular malignancies developed subsequently to testis cancer. In 4 patients, triple malignancies were observed. Bladder carcinoma and bronchogenic cancer with each 3 cases were the most frequent second neoplasms seen in these patients. 9 consecutive cancers developed within radiation fields, the median latency period in these cases was 12 years. None of the subsequent cancers developed after chemotherapy. It is concluded that genetic predisposition and radiation effects are the most important factors contributing to the occurrence of multiple primary neoplasms in patients with testicular germ cell cancer. The high rate of multiple primary neoplasms in these patients lends further evidence to the theory of genetic anticipation of germ cell cancer.

Adult↗
PubMedDate not supplied

NCAM mediates adhesion between gonocytes and Sertoli cells in cocultures from testes of neonatal rats.

During neonatal development of the rat testis, gonocytes resume mitosis and display renewed motility to migrate toward the basal lamina, two events that occur in vitro when these cells are cocultured with Sertoli cells. However, although substantial evidence suggests that development of gonocytes depends on Sertoli cells, little is known of how these cell types interact beyond our previous observations that they communicate via gap junctions and adhere avidly to each other. In the present study, we utilized several approaches to examine the mechanism by which gonocytes adhere to Sertoli cells in vitro. First, we characterized this attachment in general by (1) determining its susceptibility to brief trypsinization in decreasing concentrations of Ca2+, (2) assessing the ability of gonocytes to adhere to Sertoli cells at reduced temperature, and (3) examining the effect of phospholipase C treatment on the number of gonocytes attached to a Sertoli cell monolayer. Because the findings suggested that a non-cadherin mechanism is involved, we used immunofluorescence to identify the presence of neural cell adhesion molecule (NCAM) at virtually all gonocyte-Sertoli cell (and Sertoli cell-Sertoli cell) boundaries and found that incubation of cocultures in the continuous presence of NCAM antibodies caused release of essentially all gonocytes (but not Sertoli cells) from the monolayer. We also found, in (3) above, that gonocyte-Sertoli cell adhesion was very susceptible to phospholipase C in cocultures isolated from newborns and maintained in vitro for 2 hours or 1 day but not in cultures maintained for 3 days. Moreover, cells isolated from pups 5 days old were as resistant to enzyme treatment at 2 hours postplating as were cultures from newborns after 3 days in vitro. Thus, the way in which gonocytes adhere to Sertoli cells appears to change during the immediate postnatal period, as reflected by the observed change in phopholipase sensitivity, perhaps indicating production of a phospholipase C-resistant NCAM isoform by several days after birth. These data constitute new information on the way in which postnatal gonocytes adhere to Sertoli cells and provide a basis for future work in our ongoing exploration of germ cell development in the neonatal rat testis.

Animals↗
PubMed1994

Seminomas of the canine testis. Counterpart of spermatocytic seminoma of men?

BACKGROUND: Dogs develop germ cell tumors of the testis at a relatively high rate. It is not known to what degree these tumors resemble various human testicular neoplasms. EXPERIMENTAL DESIGN: The epidemiology and morphology of a series of spontaneous canine testicular tumors, collected between 1985 and 1991, was analyzed, and compared with human testicular germ cell tumors. DNA content analysis of representative samples was performed using flow cytometry and image cytometry. Eight human spermatocytic seminomas were studied in parallel. RESULTS: All canine tumors had the histopathologic features reported as typical for dog testis seminomas. These tumors could show both an intratubular and an invasive component. Most of them were pure (78%), while they could be combined with a Leydig cell tumor, a Sertoli cell tumor, or both. No somatic, placental or yolk sac cells were identified, and there was no carcinoma in situ (CIS). A bimodal age distribution, with a peak around 1 year of age and between 4 and 16 years of age, was found for all pure and mixed testicular tumors, except for those composed of a Leydig cell and a seminoma component. These tumors were all present in dogs older than 7 years, being significantly more older (p < 0.01) than dogs with a pure tumor of either type. All Sertoli cell and Leydig cell tumors were diploid. No consistent peritriploid DNA content, characteristic of human testicular germ cell tumors, was found for canine seminomas, which most often had a diploid DNA content. Human spermatocytic seminomas always contained diploid tumor cells, and showed a relatively low number of high ploidy cells, comparable to canine seminomas of the testis. CONCLUSIONS: The so-called seminomas of the testis are tumors of old age. Histologically, these tumors are composed of a single cell type with some variation without evidence of differentiation. It is proposed that canine seminoma correspond to human spermatocytic seminomas. It is thought that the Leydig elements in these tumors represent a reactive change rather than biphasic differentiation of a single stem cell capable of germinal and sex-cord cell development.

Animals↗
PubMed1975

Development of a Mn-2+-sensitive, "soluble" adenylate cyclase in rat testis.

A distinctive Mn-2+-sensitive adenylate cyclase [ATP pyrophosphate-lyase(cyclizing), EC 4.6.1.1] system insensitive to fluoride has been found in rat seminiferous tubules and epididymal sperm. The development of this distinctive adenylate cyclase in testis was studied during spermatogenesis. It was first detectable in seminiferous tubules in immature rats at about the time of the first reductive divisions and the appearance of spermatid cells. The specific activity of the enzyme increased substantially during the period of spermatogenesis when spermatids develop into mature spermatozoa, and reached maximal values in the testis of adult rats. After centrifugation of testis tissue homogenates at 105,000 X g for 60 min, the Mn-2+-sensitive adenylate cyclase activity was found in the cytosol. The enzyme remains in solution after centrifugation at 300,000 X g for 5 hr or at 180,000 X g for 24 hr and passes through a 0.22 mum Millipore filter. Electron microscopic examination showed no visible membrane fragments or vesicles in the filtered supernatant. The Mn-2+-sensitive adenylate cyclase system is also present in epidiymal sperm. However, in the sperm obtained from either the caput or the cauda of epididymis, the adenylate cyclase is membrane-associated and found in particulate fractions of sperm homogenates. It therefore appears that the Mn-2+-sensitive adenylate cyclase is initially present in the cytoplasm either unattached or loosely bound to intracellular membranes and becomes firmly attached to sperm membranes later in development. This occurs either during the process of maturation of spermatids into sperm or during the transport of the testicular sperm into the epididymis.

Adenylyl Cyclases↗
PubMedDate not supplied

Zfy gene expression patterns are not compatible with a primary role in mouse sex determination.

The Y chromosome determines maleness in mammals. A Y chromosome-linked gene diverts the indifferent embryonic gonad from the default ovarian pathway in favour of testis differentiation, initiating male development. Study of this basic developmental switch requires the isolation of the testis-determining gene, termed TDF in humans and Tdy in mice. ZFY, a candidate gene for TDF, potentially encodes a zinc-finger protein, and has two Y-linked homologues, Zfy-1 and Zfy-2, in mice. Although ZFY, Zfy-1 and Zfy-2 seem to map to the sex-determining regions of the human and mouse Y chromosomes, there is no direct evidence that these genes are involved in testis determination. We report here that Zfy-1 but not Zfy-2 is expressed in differentiating embryonic mouse testes. Neither gene, however, is expressed in We/We mutant embryonic testes which lack germ cells. These observations exclude both Zfy-1 and Zfy-2 as candidates for the mouse testis-determining gene.

Animals↗
PubMed2005

High dose of Garcinia cambogia is effective in suppressing fat accumulation in developing male Zucker obese rats, but highly toxic to the testis.

We investigated the ability of Garcinia cambogia extract containing (-)-hydroxycitric acid (HCA) to suppress body fat accumulation in developing male Zucker obese (fa/fa) rats. We also examined histopathologically the safety of its high doses. Diets containing different levels of HCA (0, 10, 51, 102 and 154 mmol/kg diet) were fed to 6-week-old rats for 92 or 93 days. Each diet group was pair-fed to the 154 mmol HCA/kg diet group. Epididymal fat accumulation and histopathological changes in tissues were observed. The highest dose of HCA-containing Garcinia cambogia (154 mmol HCA/kg diet) showed significant suppression of epididymal fat accumulation in developing male Zucker obese rats, compared with the other groups. However, the diets containing 102 mmol HCA/kg diet and higher (778 and 1244 mg HCA/kg BW/d, respectively) caused potent testicular atrophy and toxicity, whereas diets containing 51 mmol HCA/kg diet (389 mg HCA/kg BW/d) or less did not. Accordingly, 51 mmol HCA/kg diet (389 mg HCA/kg BW/d) was deemed to be the no observed adverse effect level (NOAEL).

ATP Citrate (pro-S)-Lyase↗
PubMed1988

Evidence for the sexual bipotentiality of spermatogonia in the fish, Oryzias latipes.

The origin of the oocyte-like cells (testis-ova) induced by the administration of estradiol in the testis of the fish, Oryzias latipes, was examined by light and electron microscopy. A small number of testis-ova at the zygotene stage was seen on the sixth day after the beginning of treatment with estradiol, and on the 12th day testis-ova at the pachytene and diplotene stages were observed. Ultrastructural observations revealed that the testis-ova at the zygotene stage were organized as cysts and that all testis-ova within a given cyst developed synchronously. The number of these testis-ova in each cyst varied but cysts containing 16-20 or 26-30 testis-ova were most frequently observed. Spermatogonia of O. latipes are classified morphologically into two types: the type A and the type B spermatogonia (Grier, '76 Cell Tissue Res., 168:419-431). Type A spermatogonia, which were separated from each other by Sertoli cells, were of the stem type and type B spermatogonia appeared to divide clonally 9-10 times in each cyst before entering meiosis. The present observations on zygotene testis-ova indicate that the testis-ova originate from type B spermatogonia which have divided clonally four or five times, suggesting that male germ cells remain sexually bipotent through the early stages of development of type B spermatogonia.

Animals↗
PubMed1999

A 1.3-kb upstream 5' region of the rat phosphoglycerate mutase m gene confers testis and skeletal muscle-specific expression in transgenic mice.

Spermatogenesis is a complex process that occurs in successive mitotic, meiotic and post-meiotic phases and involves a highly regulated selective gene-expression pattern. However, this process has not been well characterised at the gene expression level due to the absence of germinal cell lines. We previously demonstrated that the rat skeletal muscle-specific gene for the glycolytic enzyme phosphoglycerate mutase is also specifically expressed in meiotic and haploid male germ cells from testis (12). To analyse the promoter elements that regulate the transcription of the phosphoglycerate mutase m gene (pgam-m)during spermatogenesis, we developed transgenic mice for a construct containing 1.3 kb from the pgam-m promoter linked to the Escherichia coli LacZ gene. RNA analysis by retrotranscription and PCR amplification of transgene expression showed transcriptional activity in the testis with a pattern during testis development that was identical to the endogenous gene. The transgene was also active in skeletal muscle but not in the adult heart in all the transgenic lines analysed. Collectively, these studies demonstrate that the 1.3 kb pgam-m promoter contains sufficient sequences to specify temporally regulated testis-specific expression as well as skeletal-muscle expression.

Animals↗
PubMed2005

Expression and localization of growth factors and their receptors in the mammalian testis. Part I: Fibroblast growth factors and insulin-like growth factors.

It is now well established that normal development and function of testis are mediated by endocrine and paracrine pathways including hormones, growth factors and cytokines as well as by direct cell-to-cell contacts depending on tight, adhering and gap junctions. In the last two decades, several growth factors were identified in the testis of various mammalian species. Growth factors are shown to promote cell proliferation, regulate tissue differentiation, and modulate organogenesis. Interestingly, most of these peptides are expressed not only in the adult mammalian testis during spermatogenesis but also during testicular morphogenesis in prenatal and postnatal life. Our study was launched to provide an overview of the expression, localization, and putative physiological roles of growth factors and their receptors in the mammalian testis. The growth factors considered in this part of our review are fibroblast growth factors and insulin-like growth factors. These factors are found in testicular cells in prenatal, postnatal, and adult animals and are implicated in the regulation of important testicular activities including testicular cord morphogenesis, modulation of testicular hormone secretion and control of spermatogenesis.

Animals↗
PubMed1977

[Repeated amputation of the lower incisors in rats and the phenomena of salivary gland and testicular hypertrophy].

Repeated amputation of the lower incisors in rats, 11- and 14-days old, caused hypertrophy of the testis only in the presence of the submaxillary salivary glands. Bilateral submaxillary and sublingual sialadenectomy prevented hypertrophy of the testis. After the unilateral removal of these glands the weight of the testis increased, but its hypertrophy developed always. The absence of hypertrophy of the testis in the sialadenectomized animals led to the conclusion that the growth stimulating action on the testis of repeated amputations of the lower incisors was in some way mediated through the function of the salivary glands.

Animals↗
PubMed1983

Growth and differentiation of spermatogenetic colonies in the mouse testis after irradiation with fission neutrons.

The longitudinal outgrowth of spermatogenetic colonies arising from stem cells that survived neutron doses of 150, 300, and 350 rad was studied up to 30 weeks in histological sections of CBA mouse testes. Two methods were used: (1) the repopulation index (RI) as a measure of the length of total colonies per testis and (2) measurement of the individual length of all colonies in serially sectioned testes 4 and 15 weeks after 300 rad and 15 weeks after 350 rad. The mean initial growth of the colonies is linear up to 8, 15, and 20 weeks after 150, 300, and 350 rad, respectively. Although after these doses the mean initial colony growth rate did not differ significantly (about 27 microns/day), both methods showed that the colonies grow about 20% slower after 350 rad. Screening of individual colonies revealed a great variation in colony length per testis and a higher frequency of short colonies with higher neutron doses. Counting of colonies after 300 rad showed that all surviving stem cells had started to form a colony within 4 weeks after irradiation. The development of spermatogenetic cells to mature spermatozoa was studied after 100, 150, 300, and 350 rad in sections of repopulating tubules used for RI determination as well as in serial sections of individual colonies. Although after 300 and 350 rad spermatogenetic cell types beyond the stage of young spermatocytes reappeared 1 week late, we found no great disturbances in the regular reappearance of the successive spermatogenetic cell types after irradiation. However, from the study of individual colonies it appeared that colonies differ widely in their development even within one testis. Moreover, the frequency of less developed colonies was higher after 350 rad than after 300 rad. Our data suggest that this retardation in the reappearance of further developed cells is caused by a delay in the production of developed cells in spermatogonia in an increasing fraction of the colonies after higher neutron doses. Even in fully developed colonies the production of differentiating spermatogenetic cell types was subnormal after 300 and 350 rad. This was caused by an extensive cell degeneration in the colonies as well as by a tendency of the undifferentiated and/or A1-spermatogonial population to increase its own number at the cost of the production of further developed cells.

Animals↗
PubMed1983

Testicular testosterone and dihydrotestosterone during sexual development in humans.

The concentrations of testosterone and dihydrotestosterone was determined in the human testis at different stages of sexual development, in patients with undescended testis or in subjects who had been treated for acute lymphoblastic leukemia. Patients were divided in three groups, prepubertal (Tanner's stage I), early puberty (Tanner's stages 2 + 3) and late puberty (Tanner's stages 4 + 5). Even though tubular diameter and serum testosterone followed the expected gradual rise during sexual maturation, testicular testosterone increased abruptly at early puberty, resulting in a high testicular: serum testosterone ratio at this stage. The testicular dihydrotestosterone:testosterone ratio was also high at early puberty. These data suggest that, at initiation of sexual development, seminiferous tubules receive a high androgen load, at a time when other androgen target organs are barely stimulated.

Adolescent↗
PubMed1986

Regeneration of Leydig cells in unilaterally cryptorchid rats: evidence for stimulation by local testicular factors.

Leydig cells in testes of adult rats were selectively destroyed by a single intraperitoneal injection of ethane dimethane sulphonate. Four days later rats were made unilaterally cryptorchid and 1, 2 and 4 weeks later the histology of the testes were examined by light microscopy and morphometry. After induction of unilateral cryptorchidism, the volume of abdominal compared to scrotal testes was reduced by 45-60% due to rapid impairment of spermatogenesis in abdominal testes. Leydig cells were not present in either scrotal or abdominal testes in the 1-week unilateral cryptorchid group. A new generation of foetal-type Leydig cells were observed in scrotal testes of the 2-week unilateral cryptorchid group although their total volume per testis estimated by morphometry, was small, being approximately 1 microliter. In contrast, the abdominal testis exhibited a remarkable proliferation of foetal-type Leydig cells (total volume per testis, 16 microliter) which predominantly surrounded the peritubular tissues of the seminiferous tubules. A similar morphology and pattern of Leydig cell development was observed in scrotal and abdominal testes of the 4-week unilateral cryptorchid group where total Leydig cell volume was 7 microliter vs 21 microliter, respectively. The results show that regeneration of a new population of Leydig cells occurs more rapidly in the abdominal testis than in the scrotal testis of the same animal. These observations suggest the possibility that augmentation of Leydig cell growth is mediated by local intratesticular stimulatory factors within the abdominal testis. Development of new Leydig cells from the peritubular tissue provides circumstantial evidence that the seminiferous tubules and in particular the Sertoli cells, are a likely source of agents that stimulate the growth of Leydig cells.

Animals↗
PubMed2004

Wt1 functions in the development of germ cells in addition to somatic cell lineages of the testis.

The Wilms' tumor suppressor gene, Wt1, encodes a transcription factor critical for development of the urogenital system. To identify lineages within the developing urogenital system that have a cell-autonomous requirement for Wt1, chimeric mice were generated from Wt1-null ES cells. Males with large contributions of Wt1-/- cells showed hypoplastic and dysgenic testes, with seminiferous tubules lacking spermatogonia. Wt1-null cells contributed poorly to both somatic and germ cell lineages within the developing gonad, suggesting an unexpected role for Wt1 in germ cell development in addition to a role in the development of the somatic lineages of the gonad. Wt1 expression was detected in embryonic germ cells beginning at embryonic day 11.5 after migrating primordial germ cells (PGCs) have entered the gonad. Germ cells isolated from Wt1-null embryos showed impaired growth in culture, further demonstrating a role for Wt1 in germ cell proliferation or survival. Therefore, Wt1 plays important, and in some cases previously unrecognized, roles in multiple lineages during urogenital development.

Animals↗
PubMed1971

Bilateral anorchia: discordance in monozygotic twins.

The bilateral absence of testes is described in one of two otherwise healthy and well-developed 12-year-old identical twin boys. The twins' father has only one palpable testis. The occurrence of complete anorchia in only one of otherwise identical twins constitutes relevant new data for considering the etiology of this rare condition and in assaying the role of the testis in growth and development between birth and puberty.

Body Height↗
PubMed2005

Gonadal development and sex differentiation in the cichlid fish Cichlasoma dimerus (Teleostei, Perciformes): a light- and electron-microscopic study.

Although the overall pattern and timing of gonadal sex differentiation have been established in a considerable number of teleosts, the ultrastructure of early stages of gonadal development is not well documented. In this study, gonads from larval and juvenile stages of laboratory-reared Cichlasoma dimerus were examined at the light-microscopic and ultrastructural levels. This freshwater species adapts easily to captivity and spawns with high frequency during 8 months of the year, providing an appropriate model for developmental studies. Larvae and juveniles were kept at a water temperature of 26.5 +/- 1 degrees C and a 12:12 hour photoperiod. Gonadal development was documented from 14-100 days postfertilization, covering the period of histologically discernible sex differentiation. Gonadal tissue was processed according to standard techniques for light and electron microscopy. C. dimerus, a perciform teleost, is classified as a differentiated gonochorist, in which an indifferent gonad develops directly into a testis or ovary. On day 14, the gonadal primordium consists of a few germ cells surrounded by enveloping somatic cells. Ovarian differentiation precedes testicular differentiation, as usual in teleost fishes. The earliest signs of differentiation, detected from day 42 onward, include the onset of meiotic activity in newly formed oocytes, which is soon accompanied by increased oogonial mitotic proliferation and the somatic reorganization of the presumptive ovary. The ovarian cavity is completely formed by day 65. Numerous follicles containing perinucleolar oocytes are observed by day 100. In contrast, signs of morphological differentiation in the presumptive testis are not observed until day 72. By day 100, the unrestricted lobular organization of the testis is evident. The latest stage of spermatogenesis observed by this time of testicular development is spermatocyte II.

Animals↗