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At least 1,153 records · Page 64Linked to original sources
PubMed2004

Cadmium and cancer of prostate and testis.

Cancer of the prostate is an important and potentially fatal disease in humans but the etiology is yet undefined. Cadmium and cadmium compounds are known to be human carcinogens based on findings of increased risk to lung cancer among exposed workers, but a relationship between cancer of the prostate and/or testis in humans is unclear in spite of suggestive results in rats. Parenteral administration or oral exposure to cadmium can result in proliferate lesions and tumors of the prostate in rats. The ability of cadmium to produce neoplasms in the prostate of rats is atypically dose-related and only occurs in rats at doses below the threshold for significant testicular toxicity. Testicular androgen production is essential for the maintenance of the prostate and prostate tumors. The rat testis may also develop tumors if cadmium is given parenterally at high doses. Subsequent to testicular hemorrhagic necrosis, there will be loss of testosterone production and hyperplasia and neoplasia of testicular interstitial cells, thought to be a response to trophic hormone release from the pituitary. The pathogenesis of prostatic cadmium carcinogenesis might include aberrant gene expression resulting in stimulation of cell proliferation or blockage of apoptosis. Activation of transcription factors such as the metallothionein gene and activation of some protooncogenes may enhance cell proliferation with damaged DNA. Suppression of DNA repair would add to the population of cells with damaged DNA. Chemically induced apoptosis can be blocked by cadmium, facilitating aberrant cell accumulation.

Animals↗
PubMed2001

Developmental study of the different effects on the hybrid sterility of Kit and KitW-v alleles paired with Kit from Mus spretus.

The combination of the KitW or KitW-n mutant alleles and KitS from Mus spretus results in male hybrid sterility with small testes. In the present study, reproduction of the combination between KitW-v and KitS alleles was examined. The KitW-v/KitS male was fertile and the histologic structure was normal; the seminiferous tubules showed all of the normal stages of spermatogenesis. The postnatal development of the testis at 8, 12, 16 and 20 days was also studied in the fertile +Kit/+Kit and KitW-v/KitS males and the sterile KitW/KitS. The results showed that at 8 days there was no noticeable difference among the three genotype combinations, while from 12 to 20 days spermatogenesis in the KitW/KitS male nearly stopped before the meiosis stage. The expression of Kit receptor protein from the KitS allele in the sterile testis of the KitW/KitS male was confirmed using western blot analysis. The Kit ligand derived from M. spretus showed two amino acid changes in the extracellular domain compared with that from C57BL and it appears that the ligand-receptor interaction between C57BL and SPR may influence the male hybrid sterility of KitW/KitS.

Alleles↗
PubMed1996

The influence of temperature on changes in pH, lactate and morphology during testicular ischaemia.

OBJECTIVE: To examine the role of temperature in the irreversible changes that occur within 4-6 h as ischaemic atrophy develops in the testis during testicular torsion, by determining effects on testicular pH, lactate accumulation and morphology. MATERIALS AND METHODS: Tissue acidification (pH), tissue lactate and structural changes were measured at temperatures of 35, 25, 15 and 5 degrees C in 34 human testes obtained as orchidectomy specimens from patients with metastatic prostatic cancer, and in 19 testes taken from young dogs. RESULTS: At a normal testicular temperature of 35 degrees C, the pH decreased to 6.0 within 2 h of the onset of ischaemia; cooling to 15 degrees C extended this delay to 6 h. Tissue lactate increased from 25 mumol/g dry weight to about 200 mumol/g at 35 degrees C. Semi-thin sections of the canine testes showed swelling of the intratubular tissue with loss of interstitial space; lower temperature delayed these changes. CONCLUSIONS: In the present study, 6 h of torsion was relatively prolonged, in that the pH decreased to 5.8 and testicular tissue was destroyed. Acidification and histological damage can be prevented by cooling. The critical pH of the testis beyond which irreversible changes occur is unknown; a pH of < 6.0 is likely to provoke such changes.

Aged↗
PubMed2005

LGR8 signal activation by the relaxin-like factor.

The relaxin-like factor (RLF) is thought to be responsible for the intra-abdominal migration of the testis during mammalian development. Our latest studies of RLF and LGR8 have revealed that the N-terminal region of the A chain is not required for receptor binding but is indispensable for cyclic AMP generation. RLF derivatives with six residues deleted from the N terminus of the A chain are active, whereas further truncation, up to the first A chain cysteine (A-10), yields tightly binding ligands devoid of signaling activity. These derivatives are specific competitive inhibitors (RLFi) of RLF. Although receptor binding is dependent upon B chain residues, the N-terminal region of the A chain is a generic trigger of the trans-membrane signaling activity.

Amino Acid Sequence↗
PubMedDate not supplied

Does orchidopexy revert the histological alterations in epididymal and vas deferens caused by cryptorchidism?

Cryptorchidism is a pathological condition in which the testicles are retained in the abdominal cavity, resulting in atrophic seminiferous tubules. Some gross structural abnormalities and histological altercations have been described in the epididymis and vas deferens in humans with cryptorchidic testes. Orchidopexy surgery restores testicular spermatogenesis in experimental and clinical procedures, but it is still unclear whether histological changes in the epididymis and vas deferens caused by cryptorchidism may be reverted by orchidopexy. The aim of this study was to evaluated the histological changes in the epididymis and vas deferens following experimental uni- bilateral cryptorchidism in mature and immature mice, and to determine whether altercations could be reversed by orchidopexy. Young and adult C57 BL6 mice were randomized into three groups: control mice, bi/unilaterally cryptorchidic mice and bilaterally cryptorchidic mice with orchidopexy. After evaluation of testis, epididymis and vas deferens, there were no histological alterations in contralateral epididymis of mice unilaterally cryptorchidic. Ipsilateral epididymis of unilaterally cryptorchidic mice and epididymis from bilaterally cryptorchidic mice showed significant histological alterations. Orchuidopexy resorted normal spermatogenesis and the histological features of epididymis. It would appear that persistent male infertility clinically observed after orchidopexy could not be related to histological alteration in the testis and epididymis. Development and maintenance of the vas deferens seems to be controlled independently of the epididymis since it was not altered by cryptorchidism condition.

Animals↗
PubMed1999

Claudin-11/OSP-based tight junctions of myelin sheaths in brain and Sertoli cells in testis.

Members of the newly identified claudin gene family constitute tight junction (TJ) strands, which play a pivotal role in compartmentalization in multicellular organisms. We identified oligodendrocyte-specific protein (OSP) as claudin-11, a new claudin family member, due to its sequence similarity to claudins as well as its ability to form TJ strands in transfected fibroblasts. Claudin-11/OSP mRNA was expressed in the brain and testis. Immunofluorescence microscopy with anti-claudin-11/OSP polyclonal antibody (pAb) and anti-neurofilament mAb revealed that in the brain claudin-11/OSP-positive linear structures run in a gentle spiral around neurofilament-positive axons. At the electron microscopic level, these linear structures were identified as the so-called interlamellar strands in myelin sheaths of oligodendrocytes. In testis, well-developed TJ strands of Sertoli cells were specifically labeled with anti-claudin-11/OSP pAb both at immunofluorescence and electron microscopic levels. These findings indicated that the interlamellar strands of oligodendrocyte myelin sheaths can be regarded as a variant of TJ strands found in many other epithelial cells, and that these strands share a specific claudin species, claudin-11/OSP, with those in Sertoli cells to create and maintain the repeated compartments around axons by oligodendrocytes.

Animals↗
PubMed2004

Sry associates with the heterochromatin protein 1 complex by interacting with a KRAB domain protein.

In mammals, the SRY/Sry gene on the Y chromosome is necessary and sufficient for a bipotential gonad to develop into a testis, regardless of its chromosomal sex. The SRY/Sry gene encodes a protein that belongs to a high-mobility-group (HMG) box protein family and that has been postulated to modulate the expression of genes necessary for male gonadal differentiation. Using a yeast two-hybrid screen, we identified a novel protein containing only a Krüppel-associated box (KRAB) domain, which is hereafter named KRAB-O (KRAB Only), as an SRY-interacting protein. The KRAB-O protein is encoded by an alternatively spliced transcript from the Zfp208 locus that also produces another transcript coding for a KRAB-zinc finger protein, ZFP208. The interaction of the mouse SRY with KRAB-O was further confirmed by glutathione S-transferase pull-down assay and coimmunoprecipitation in transfected COS7 cells. The KRAB-O interaction domain in both the human and mouse SRY was mapped to the bridge region outside the HMG box. Indirect immunofluorescence and confocal microscopy show that the mouse SRY colocalizes with KRAB-O in nuclear dots in transiently transfected COS7 cells and primary fetal mouse gonadal cells. Using similar approaches, we demonstrate that KRAB-O interacts directly with KAP1 (KRAB-associated protein 1), the obligatory corepressor for KRAB domain proteins. Furthermore, we show that the mouse SRY is associated indirectly with KAP1 and heterochromatin protein 1 (HP1) through its interaction with KRAB-O, suggesting that the mouse SRY could use the KRAB-KAP1-HP1 organized transcriptional regulatory complex to regulate its yet-to-be-identified downstream target genes.

Amino Acid Sequence↗
PubMed1989

Stimulation of spermatocyte development in prepubertal rats by the Sertoli cell steroid, 3 alpha-hydroxy-4-pregnen-20-one.

The effect of 3 alpha-hydroxy-4-pregnen-3-one (3HP), a Sertoli cell steroid, on spermatogenesis was examined in normal and gonadotropin-suppressed rats, through s.c. as well as direct intratesticular injections. Early experiments employing normal prepubertal male rats indicated that 3HP, when administered at 65 micrograms/100 g BW daily for 15 days, was capable of stimulating pachytene spermatocyte number to 149% of untreated control numbers. It was of interest to determine if this effect could be amplified in gonadotropin-suppressed animals. Neonatally estrogenized rats (500 micrograms estradiol benzoate in 0.1 ml oil at 2 days) were treated on alternate days with 3HP (100 micrograms/100 g BW) for 3 wk, starting at 7 days of age. This treatment significantly increased the number of spermatocytes per tubule cross section from 17.3 +/- 1.9 (in estradiol benzoate-only animals) to 47.1 +/- 7.9 (p less than 0.01). In a similar study, 100 micrograms/100 g BW of testosterone propionate could stimulate spermatocyte number to only 15.1 +/- 2.2 cells per tubule cross section versus estradiol benzoate-only numbers. A single intratesticular injection of 3HP (2 ng in 2.0 microliters oil) in Methallibure-treated rats resulted in a significant increase in late pachytene spermatocyte numbers from 0.77 +/- 0.12 in Methallibure-only-treated rats to 1.70 +/- 0.10 (p less than 0.001) cells per tubule cross section in 28-day-old rats. However, in this study, no other progesterone metabolite or androgenic steroid (testosterone, 5 alpha-dihydrotestosterone, or 5 alpha-androstan-3 alpha, 17 beta-diol) tested was capable of this level of germ cell stimulation. In conclusion, 3HP appears to have a direct effect on germ cell development within the testis at levels much lower than those shown to be effective for androgens. It does not appear that this effect is mediated through the conversion of 3HP to any C21 or C19 steroids, and appears to be the first report of a Sertoli cell steroid with a possible role in the process of mammalian spermatogenesis.

20-alpha-Dihydroprogesterone↗
PubMed1989

A novel maturation marker for human Sertoli cells.

The maturation of Sertoli cells at puberty is critical for the initiation and maintenance of spermatogenesis. Little is known about the factors which control Sertoli cell maturation. We have examined Sertoli cells in testicular specimens from 44 subjects, ranging in age from 6 months to 67 years, for reactivity with a mouse monoclonal antibody (M2A) using the immunoperoxidase reaction. We found positive reactivity with prepubertal but not postpubertal Sertoli cells, suggesting that the antigen defined by M2A was a marker of immature Sertoli cells. This marker may be useful for studying the factors which influence Sertoli cell maturation during development of the testis.

Adolescent↗
PubMedDate not supplied

Intratubular germ cell tumours of pig testicles.

In the course for the histopathological examination of testicles of 30 castrated boars the authors have observed in 4 animals the intratubular growth of atypical germ cells. On the basis of the histological picture this change is equivalent to the human infertile testicles, observed as carcinoma in situ, resp. intratubular germ cell tumour. The described phenomenon occurred in atrophic testicles in 3 of the 4 old animals. The described change in the domestic pig, not known so far, raises the possibility of development of solid testis tumours in this species, as well.

Animals↗
PubMed1998

Combinations of growth promoters in veal calves: consequences for screening and confirmation methods.

This study investigates the influence of low dosages of beta-agonists combined with other growth promoters on screening and confirmation methods in male veal calves. Five groups of four calves were treated for 6 weeks with combinations of low dosages of beta-agonists (beta AG, clenbuterol, mabuterol and mapenterol, 0.4 microgram/kg each twice daily) in combination with 17 beta-estradiol (E2, 5 mg per animal per 14 days), methylthiouracil (MTU, 2.857 mg/kg bw twice daily) and dexamethasone (DEX, 4 mg per animal per 10 days during the last 20 days of treatment). Another group of four untreated animals served as controls. The weight and size of the thymus was reduced in the DEX group, the MTU group showed enlarged thyroids. Histologically the prostates showed vacuolar degeneration in the beta AG animals and metaplasia in the E2 group. Some vacuolization was also observed in the controls. The testis showed impaired development in all treatment groups, E2 leading to the most severe changes. DEX led to cortical atrophy of the thymus. MTU induced hyperplastic changes in the thyroid. These results indicate that comedication does not markedly affect the histological changes induced in the hormonal target tissues. For screening purposes histology of the prostate can be used as a marker for oestrogens, whereas the weight of the thymus and thyroid can be used as an indication for the use of corticosteroids and thyreostatics, respectively. Vacuolization in the prostate appeared no reliable indication for beta-agonists. Samples of urine, faeces, liver and eye (retina/choroid) were analysed for beta-agonists. E2 significantly increased the levels of all beta-agonists in the liver and faeces, whereas DEX significantly reduced these levels. These observations show that additional medication with different groups of growth promoters can markedly alter the excretion of beta-agonists and thus influence (regulatory) control.

2-Hydroxyphenethylamine↗
PubMed2004

Expression of p57 in mouse and human testes.

The expression of cyclin-dependent kinases inhibitors, p57kip2, was investigated during the postnatal development of mouse testis, and in adult human testis. Expression of p57kip2 mRNA was higher in immature than pubertal or adult mouse testes. In postnatal day 7 (PND7) testes, moderate p57kip2 immunoreactivity was found in spermatogonia, but signal was heterogeneous among the spermatogonia. In PND14 testes onward, strong immunoreactivity of p57kip2 was found in the nuclei of early spermatocytes but not in the late pachytene stage onward. In PND28 and PND50 testes, p57kip2 immunoreactivity was varying among the seminiferous tubules. There was no visible signal in late pachytene stage onward. In Leydig cells, heterogeneous immunoreactivity of p57kip2 was found in immature testis and the signal intensity was higher in adult testis than immature ones. In Sertoli cells, weak or negligible immunoreactivity of p57kip2 was found. In human seminiferous tubule, strong immunoreactivity of p57kip2 was found in the nucleus of early spermatocytes, but not in the late pachytene spermatocytes onward and Sertoli cells. These results suggest the possible role of p57kip2 in the regulation of early spermatogonial proliferation, meiotic progression of early spermatocytes and differentiation of Leydig cells in testis.

Animals↗
PubMed1998

Developmental arrest of germ cells in the pathogenesis of germ cell neoplasia.

Clinical observations and epidemiological evidence suggest that important aetiopathological events that cause neoplastic transformation of the male germ cell may occur in fetal life or early infancy. The incidence of germ cell neoplasia is high in individuals with various disorders of gonadal development and sexual differentiation, such as gonadal dysgenesis or androgen insensitivity syndrome. Increased risk has also been noted in individuals with trisomy 21, idiopathic infertility and low birth weight. Infertility is sometimes associated with small aberrations of sex chromosomes (e.g. low frequency mosaicism XY/XO) which can also be found in patients with testicular cancer. The variety of conditions that predispose to testicular neoplasia and the rise in its incidence in many countries speaks for the influence of environmental factors which may affect genetically predisposed individuals. We hypothesise that if the development of the testis is disturbed or delayed, primordial germ cells or gonocytes undergo maturation delay or differentiation arrest which may render them susceptible to neoplastic transformation. Morphologically homogenous premalignant carcinoma in situ (CIS) cells have the potential to differentiate into a variety of histological forms of overt testicular tumours. Analysis of cell surface antigens expressed by CIS cells found in the vicinity of pure and mixed tumours demonstrates that CIS cells are phenotypically heterogeneous. Comparison of the phenotypes of CIS cells, primordial germ cells, human embryonal carcinoma cells and closely related primate embryonal stem cells reveals various similarities but also differences. We speculate that phenotypical heterogeneity of CIS cells may be associated with their potential to give rise to different tumour types, and may be related to the developmental stage of the early germ cell which has undergone malignant transformation.

Adult↗
PubMed1998

X-linked sex-reversing genes.

Rearrangement of the X chromosome generates fertile XY females in the wood lemming, and a duplication has been discovered in Xp21 in some XY females in the human. This has enabled identification and mapping of a novel sex-reversing gene in the human, double dosage of which blocks development of the testis. Whether or not the human gene is related to the gene that causes sex reversal in the wood lemming remains to be seen. Yet similar genes must exist in all eutherian mammals, according to Ohno's Law.

Animals↗
PubMed2004

Genomic organization and the tissue distribution of alternatively spliced isoforms of the mouse Spatial gene.

BACKGROUND: The stromal component of the thymic microenvironment is critical for T lymphocyte generation. Thymocyte differentiation involves a cascade of coordinated stromal genes controlling thymocyte survival, lineage commitment and selection. The "Stromal Protein Associated with Thymii And Lymph-node" (Spatial) gene encodes a putative transcription factor which may be involved in T-cell development. In the testis, the Spatial gene is also expressed by round spermatids during spermatogenesis. RESULTS: The Spatial gene maps to the B3-B4 region of murine chromosome 10 corresponding to the human syntenic region 10q22.1. The mouse Spatial genomic DNA is organised into 10 exons and is alternatively spliced to generate two short isoforms (Spatial-alpha and -gamma) and two other long isoforms (Spatial-delta and -epsilon) comprising 5 additional exons on the 3' site. Here, we report the cloning of a new short isoform, Spatial-beta, which differs from other isoforms by an additional alternative exon of 69 bases. This new exon encodes an interesting proline-rich signature that could confer to the 34 kDa Spatial-beta protein a particular function. By quantitative TaqMan RT-PCR, we have shown that the short isoforms are highly expressed in the thymus while the long isoforms are highly expressed in the testis. We further examined the inter-species conservation of Spatial between several mammals and identified that the protein which is rich in proline and positive amino acids, is highly conserved. CONCLUSIONS: The Spatial gene generates at least five alternative spliced variants: three short isoforms (Spatial-alpha, -beta and -gamma) highly expressed in the thymus and two long isoforms (Spatial-delta and -epsilon) highly expressed in the testis. These alternative spliced variants could have a tissue specific function.

Alternative Splicing↗
PubMed2005

Restricted expression of LGR8 in intralaminar thalamic nuclei of rat brain suggests a role in sensorimotor systems.

LGR8 was recently identified as a cognate receptor for insulin-like peptide-3 (INSL3), and INSL3-LGR8 signaling is best known for its role in testis descent during development. LGR8 mRNA has been detected in various human tissues including brain, but the regional and cellular distribution of LGR8 expression in the mammalian central nervous system is unknown. Therefore, in this study we investigated the presence and localization of LGR8 mRNA in rat brain using reverse transcription-polymerase chain reaction and in situ hybridization histochemistry. Results revealed a distinct distribution of LGR8 in forebrain, with transcripts principally restricted to the posterior thalamus and highest densities detected in the parafascicular nucleus of both adult and developing rats. Unexpectedly, INSL3 mRNA was not detected in brain by similar methods, but preliminary electrophysiologic studies of parafascicular neurons revealed that INSL3 altered their activity. These findings suggest that LGR8 signaling may be involved in sensorimotor control in the rat and perhaps other species, particularly via actions on parafascicular neurons that project to basal ganglia and are depleted in Parkinson's disease.

Aging↗
PubMed1993

Is infancy a quiescent period of testicular development? Histological, morphometric, and functional study of the seminiferous tubules of the cebus monkey from birth to the end of puberty.

The objective of this study was to describe the maturational changes observed in the seminiferous tubules of the monkey Cebus apella, a New World primate species, from birth to the end of puberty. Nineteen animals were subdivided into four groups: neonatal (1-40 days), infantile (4 months to 1 yr), early pubertal (1 yr, 8 months to 2 yr, 9 months), and late pubertal (4-8 yr). Volumetric determinations of different testicular components were made, tubule diameter and length were calculated, and spermatogenic cells, Sertoli cells, and androgen-binding protein secretion were quantified. Testicular and seminiferous tubule volumes increased significantly in the first 5 months of life and during puberty due to the combined increment in seminiferous tubule diameter and length. The total number of spermatogonia increased until late puberty to stabilize subsequently. Spermatocytes and spermatids appeared during puberty and increased dramatically until the end of this period. The germ cell ratios, indicative of spermatogenic efficiency, improved continuously in late puberty coincidentally with a reduction of spermatocyte degeneration. Sertoli cells proliferated in the neonatal and infantile periods, determining a longitudinal growth of the seminiferous tubules, but remained stable during puberty, when androgen-binding protein secretion increased significantly. The multiplication of germ cells is the main factor responsible for the increment in tubule diameter during puberty and determines the most noticeable postnatal modification of testicular volume. During late puberty, the reduction of spermatocyte degeneration leads to an increment in germ cell ratios and a progressive, but slow, improvement of spermatogenic efficiency, explaining why pubertal development of the testis occurs over such a prolonged period in this primate. This is in contrast to what happens in most laboratory animals and suggests that the Cebus is a useful model for studies of human male puberty.

Aging↗