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At least 811 records · Page 45Linked to original sources
PubMed2000

Defective mesonephric cell migration is associated with abnormal testis cord development in C57BL/6J XY(Mus domesticus) mice.

During the critical period of mouse sex determination, mesenchymal cells migrate from the mesonephros into the adjacent developing testis. This process is thought to initiate cord development and is dependent on Sry. The presence of Sry, however, does not always guarantee normal testis development. For example, transfer of certain Mus domesticus-derived Y chromosomes, i.e., M. domesticus Sry alleles, onto the C57BL/6J (B6) inbred mouse strain results in abnormal testis development. We tested the hypothesis that mesonephric cell migration was impaired in three cases representing a range of aberrant testis development: B6 XY(AKR), B6 XY(POS), and (BXD-21 x B6-Y(POS))F1 XY(POS). In each case, mesonephric cell migration was abnormal. Furthermore, the timing, extent, and position of migrating cells in vitro and cord development in vivo were coincident, supporting the hypothesis that mesonephric cells are critical for cord development. Additional experiments indicated that aberrant testis development results from the inability of Sry(M. domesticus) to initiate normal cell migration, but that downstream signal transduction mechanisms are intact. These experiments provide new insight into the mechanism of C57BL/6J-Y(M. domesticus) sex reversal. We present a model incorporating these findings as they relate to mammalian sex determination.

Animals↗
PubMed2002

Metabolism and toxicity of trichloroethylene in epididymis and testis.

The widespread occupational exposure to trichloroethylene (TCE) led us to test the hypothesis that TCE causes toxicity in the male reproductive system. We also investigated mechanisms mediating the potential cytotoxic response. Mice were exposed to TCE (1000 ppm) by inhalation for 6 h/day for 5 days/week for a total of 19 days. Exposure after the first week was interspersed by a "weekend." To estimate internal exposure, we measured the TCE metabolites, trichloroacetic acid (TCA) and trichloroethanol (TCOH), in urine at Days 4, 9, 14, and 19. Urinary excretion of TCOH was significantly higher than TCA; levels of TCOH and TCA significantly increased by the second and third week, respectively. Cytochrome P450 2E1 (CYP2E1), an enzyme involved in TCE metabolism, was localized in the epididymal epithelium and testicular Leydig cells, and was found at higher levels in the former than the latter. Immunoblotting confirmed that CYP2E1 protein was present in greater amounts in epididymis than in testis. p-Nitrophenol hydroxylation, a CYP2E1 catalytic activity, was also higher in the epididymis than in the testis. Chloral, a major TCE metabolite, was generated in microsomal incubations at significantly higher levels in epididymis than in testis. Antibody inhibition of CYP2E1 reduced chloral formation, which was more pronounced in epididymis than in testis. After 4 weeks of TCE exposure, damage to the epididymis was manifested as sloughing of epithelial cells. These results indicated that TCE is metabolized in the male reproductive tract, leading to adverse effects that are more severe in the epididymis than in the testis.

Administration, Inhalation↗
PubMed1997

Fetal and perinatal influence of xenoestrogens on testis gene expression.

The incidence of reproductive abnormalities in the male has been reported to have increased during the past 50 years. It has been suggested that these changes may be attributable to the presence of chemicals with oestrogenic activity in our environment. The aim of the experiments described in this chapter was to investigate the effects of acute exposure to high levels of xenoestrogens either indirectly during fetal life, or directly during neonatal life, on gene expression in the testis and pituitary. Fetal treatment involved administration of diethylstilbestrol (DES), 4-octylphenol (OP) or vehicle (oil, control) to pregnant rats on days 11.5 and 15.5 post coitum; fetuses were recovered on day 17.5. There was no difference between fetuses from control and treated mothers in either the overall histology of the testes or numbers of Leydig cells as determined by immunohistochemistry with an antibody directed against 3 beta-HSD. However there was a consistent and striking reduction in the amount of P450 17-a hydroxylase C17, 20 lyase (P450c17) and steroidogenic factor 1 (SF-1) detected by immunocytochemistry in testes from treatment groups given the higher doses of OP and DES. Oestrogen receptors (ER alpha) were present in the fetal leydig cells of all animals. Neonatal treatment involved direct injection of oil (control), DES, OP or Bisphenol A (Bis A) on days 2, 4, 6, 8, 10 and 12; pituitaries and testes were recovered on day 18. Testis weights and seminiferous tubule diameters were significantly reduced in animals treated with DES. In these same animals immunocytochemical localisation revealed that the amounts of FSH beta subunit and inhibin alpha subunit were reduced in their pituitaries and testes respectively. OP did not appear to have an acute, measurable effect on testis gene expression but a reduction in testis weight was noted in adult animals given the same treatment regime. The effects observed are consistent with negative feedback by oestrogens on pituitary production of FSH resulting in retarded maturation of seminiferous tubules and reduced Sertoli cell numbers. These studies have demonstrated that administration of high levels of oestrogens can affect gene expression in the testis early in life. However, the relevance of these findings to observations in man await a) a greater understanding of the physiological role(s) of oestrogens in normal males, b) an evaluation of the sources, routes of exposure, concentrations in vivo and bioavailability of xenoestrogens.

Animals↗
PubMed1984

The effects on the rat testis of single inhalation exposures to ethylene glycol monoalkyl ethers, in particular ethylene glycol monomethyl ether.

The effects of a single inhalation exposure to the rat of the saturated vapours derived from four ethylene glycol monoalkyl ethers have been investigated. No effects on the testis were observed following exposure to ethylene glycol isopropyl ether (EG ISOPE) and ethylene glycol butyl ether (EGBE), but there were marked reductions in testicular weight 14 days after exposure to ethylene glycol monomethyl ether (EGME) and ethylene glycol monoethyl ether (EGEE). Further studies were designed to establish the effect of a single exposure to EGME. Mature male albino rats were exposed to various levels of EGME vapour for a single 4-h period and killed 14 days later. Following this single exposure a dose-related decrease in testis weight was observed in rats exposed to 5,000, 2,500 or 1,250 ppm EGME. Histopathological examination revealed disordered spermatogenesis and tubular atrophy in these animals. Minimal degenerative changes were seen in the testis of rats exposed to 625 ppm EGME. When rats were examined at various time intervals after exposure to EGME vapour for 4 h, testis weight was reduced in rats examined 2 days after exposure to 2,500 and 1,000 ppm EGME and remained depressed when compared with control values for up to 19 days following exposure. Histopathological examination of the testis revealed disordered spermatogenesis in exposed animals evident at 1 day following exposure to either 2,500 or 1,00 ppm EGME.

Animals↗
PubMed1987

Origin of regenerating Leydig cells in the testis of the adult rat. An ultrastructural, morphometric and hormonal assay study.

Ethane dimethanesulphonate (EDS) was used as a specific cytotoxin to eliminate the Leydig cell population of the adult rat testis. Ultrastructural, morphometric and serum gonadotrophin and testosterone analysis was used to study the response of the intertubular tissue of the testis from 1 day to 10 weeks after EDS treatment. In control animals, the testis contained approximately 28 million Leydig cells and 8 million macrophages. Three to seven days after EDS treatment, Leydig cells were absent and serum testosterone was undetectable. Macrophage numbers increased three-fold by 3 days and returned to pretreatment values thereafter. At 2 and 3 weeks post-EDS, foetal-type Leydig cells (approximately 1-2 million per testis) appeared in proximity to perivascular and peritubular tissues, a feature also observed at 4 weeks when numerous such cells (approximately 15 million per testis) formed prominent clusters in perivascular and peritubular locations. Between 6 and 10 weeks after EDS treatment, the foetal-type Leydig cells were transformed morphologically into adult-type Leydig cells, they occupied central intertubular positions and their numbers were restored to pretreatment values. Regeneration of Leydig cells was reflected by elevated serum testosterone levels which returned towards the normal range. The results demonstrate the regenerative capacity of the testicular intertubular tissue and indicate a dual site of origin of Leydig cells which initially resemble foetal-type Leydig cells prior to establishing the adult-type Leydig cell population. The morphological pattern of Leydig cell regeneration suggests that in addition to gonadotrophic stimulation, local testicular factors from the seminiferous tubules may stimulate Leydig cell growth.

Animals↗
PubMed1992

Testosterone and FSH have independent, synergistic and stage-dependent effects upon spermatogenesis in the rat testis.

Adult rats were hypophysectomized and treated with ethane dimethanesulphonate (EDS) selectively to eliminate the Leydig cells in the testis. By removing the source of endogenous gonadotrophins and androgens, the subsequent effects on the seminiferous epithelium were studied after 20 days of treatment with vehicle, or FSH (2 x 50 micrograms/day) or a low dose of testosterone (0.6 mg testosterone esters every 3rd day) alone or in combination. Compared to vehicle-treated hypophysectomized rats with Leydig cells, testis weight in saline-treated hypophysectomized rats treated with EDS declined by 50%, spermatogenesis was disrupted severely and only 18% of the tubules contained spermatids, these being confined to stages I-VI of the spermatogenic cycle. Treatment with either FSH or testosterone esters alone significantly (P less than 0.01) increased testis weight compared to vehicle-treated hypophysectomized rats treated with EDS and 40% of tubules contained spermatids either at stages I-VI after FSH, or at all stages I-XIV after testosterone treatment. Treatment with FSH and testosterone esters together maintained testis weights approximately 20% above vehicle-treated hypophysectomized controls; over 70% of the seminiferous tubules contained spermatids and there was a marked stimulation of spermatogenesis at all stages of the spermatogenic cycle. The results suggest, that in the absence of the pituitary gland and the Leydig cells, FSH alone partially supports spermatogenesis up to the development of round spermatids whereas testosterone is capable of maintaining spermatid development at all 14 stages of the cycle. When FSH and testosterone were administered in combination, the effects upon spermatogenesis were far greater than the response expected if their individual effects were simply additive. It is therefore concluded that FSH may play a role in normal spermatogenesis and that this role is essentially that of augmenting the response of the testis to testosterone. The biochemical mechanisms via which this might occur are discussed and hypophysectomized rats treated with EDS used in the present studies should provide a useful approach for their identification.

Animals↗
PubMed1994

Analysis of cDNA sequences from mouse testis.

Few mammalian proteins involved in chromosome structure and function during meiosis have been characterized. As an approach to identify such proteins, cDNA clones expressed in mouse testis were analyzed by sequencing and Northern blotting. Various cDNA library screening methods were used to obtain the clones. First, hybridization with cDNA from testis or brain allowed selection of either negative or differentially expressed plaques. Second, positive plaques were identified by screening with polyclonal antisera to prepubertal testis nuclear proteins. Most clones were selected by negative hybridization to correspond to a low abundance class of mRNAs. A PCR-based solid-phase DNA sequencing protocol was used to rapidly obtain 306 single-pass cDNA sequences totaling more than 104 kb. Comparison with nucleic acid and protein databases showed that 56% of the clones have no significant match to any previously identified sequence. Northern blots indicate that many of these novel clones are testis-enriched in their expression. Further evidence that the screening strategies were appropriate is that a high proportion of the clones which do have a match encode testis-enriched or meiosis-specific genes, including the mouse homolog of a rat gene that encodes a synaptonemal complex protein.

Amino Acid Sequence↗
PubMed1985

Nonspecific esterases of mammalian testis. Comparative studies on the mouse (Mus musculus) and rat (rattus norvegicus).

Ten different nonspecific esterases in both mouse (Mus musculus) and rat (Rattus norvegicus) testis were identified following the analysis of electrophoretic patterns using genetic, developmental, and biochemical criteria. None of the enzymes were unique to testis, although the pattern of activity was testis specific. The enzymes comprised, in each species, six carboxylesterases (EC 3.1.1.1), one arylesterase (EC 3.1.1.2), one acetylesterase (EC 3.1.1.6), and two butyrylesterases (tentative designation). Cholinesterase (EC 3.1.1.8) was not detected. Individual homology relationships were recognized between the two species for all of these activities, except three of the carboxylesterases; however, these were coded for by homologous gene clusters. Similarities between the two species extended to the developmental course of expression and the modulation of the pattern of activity by the testicular feminization (Tfm) mutation. We describe the effects of the sex reversal (Sxr) mutation in the mouse, as well as the distribution of individual activities between Leydig cells and seminiferous tubules. The results of earlier histochemical studies are interpreted in the light of the present investigation. The correspondence between mouse- and rat-testis esterases suggests that the results could serve as a basis for mammalian testis esterase systems in general.

Acetylesterase↗
PubMed1990

Goat testis calmodulin: purification and physicochemical characterization.

Calmodulin has been purified in large quantities from goat (Capra hiscus) testis. The procedure includes heat treatment, hydrophobic interaction chromatography, and gel filtration. Goat testis calmodulin closely resembles other mammalian testis calmodulin studied so far. The protein has an extinction coefficient value (E1%1cm) of 2.09 at 280 nm, a Stokes radius of 23.2 A at 0.15 M KCl, and a frictional ratio of 1.38. Ca2+, and Tb3+ binding studies demonstrate that the protein has four Ca2(+)-binding sites with a Kd of 52.5 microM. Goat testis calmodulin shows close similarity to other calmodulins in the amino acid composition and in demonstrating an altered migration on SDS/PAGE upon Ca2+ binding. The protein also exhibits anomalously high values for molecular weight and Stokes radius as determined from the analytical gel chromatography and a change in its elution volume with the change of salt concentration in the eluant. These results have been discussed in view of the recently available knowledge from the crystallographic studies of rat testis calmodulin.

Amino Acids↗
PubMed1977

Biological damage in testis by iodine-125 in partially blocked thyroid of rats.

Degeneration of testis has been observed after administration of Iodine-125 in potassiumperchlorate treated rats. Histological damage is associated with loss of DNA, RNA, acid phosphatase, total adenosine triphosphatase (ATPase) and Na/K dependent ATPase. Iodine-125 induced atrophic testis shows higher content of sodium and lower levels of potassium as compared to control testis. Damage of testis by Iodine-125 has been compared with atrophied testis, following gamma irradiation earlier reported. Auger effect due to Iodine-125 decay and transmutation at the sites of nuclei and plasma membrane of germinal cells seems to be the possible explanation for testicular damage caused by Iodine-125.

Acid Phosphatase↗
PubMed1990

Zinc deficiency and dipeptidyl carboxypeptidase activity. Comparative effects on epididymis and testis of rats.

Dipeptidyl carboxypeptidase (DC) is highly active in the testis and epididymis of rats and increases during pubertal development. Zinc deficiency during this period depresses the activity of DC in the testis. Experiments were conducted to determine the effects of zinc deficiency on epididymal DC activity. Comparisons were made between changes seen in this organ and those observed in testis. Three dietary treatments were used; zinc-deficient, fed ad libitum; zinc-adequate, pair-fed to the deficient group; and zinc-adequate, fed ad libitum. Results confirmed that testicular DC is affected negatively by zinc deficiency. DC activity was also lower in the epididymis of zinc-deficient rats than in control rats. These effects apparently were specific relative to changes in activity of other enzymes. Alkaline phosphatase activity in the epididymis was not affected by zinc deficiency and it was depressed in the testis. Gamma-glutamyl transferase activity in the epididymis was not affected by zinc deficiency but it was elevated in the testis. The results of this study suggest that part of the effect of zinc deficiency on sexual maturity in the male rat may be caused by reduced activity of DC. This enzyme is thought to be required for maturation and development of sperm cells.

Alkaline Phosphatase↗
PubMed1989

Comparative binding of FSH to chicken and rat testis.

The binding characteristics of two highly purified preparations of follicle-stimulating hormone (FSH), one from equine (e) and one from porcine (p), were compared in a chicken testis radioreceptor assay. A two-component binding model was adequate to explain the binding of eFSH or pFSH to the chicken testis homogenate (CTH) FSH binding sites in the Scatchard study. The affinity of eFSH for the FSH binding site of CTH was 10-fold greater than that of pFSH by Scatchard analysis. This is consistent with the observation that in competitive protein binding studies approximately 10-fold greater quantities of pFSH were required to displace [125I] eFSH from the CTH FSH binding site than eFSH. Qualitatively, the order of relative potencies for various gonadotropin preparations was the same in either the CTH or a rat testis receptor radioligand assay. However, quantitatively, higher potency estimates were obtained with the CTH. The ability of LH preparations to displace radioiodinated pFSH or eFSH from CTH was generally very low with the notable exception of equine LH. The relative potency of highly purified eLH was approximately equal to that of the NIH-FSH-S16 standard (0.906 x NIH-FSH-S16) indicating that in the chicken, as in the rat, (Bousfield and Ward, Biochim. Biophys. Acta 885: 327, 1986), eLH has significant FSH activity. It is concluded that the chicken testis is a convenient and suitable source of FSH receptor (binding sites) for the bioassay of FSH, but that quantitative estimates of potency are not directly comparable when different sources of receptor are used. Finally the data show that eFSH has intriguing structural attributes which provide higher affinity to the chicken testis receptor than pFSH.

Animals↗
PubMed2005

Does testis weight decline towards the Subarctic? A case study on the common frog, Rana temporaria.

Interpopulation comparisons of variation in resource availability and in allocation patterns along altitudinal and latitudinal gradients allow insights into the mechanisms shaping the life history of animals. Patterns of between-population differences in female life history traits have been studied intensively across a wide range of taxa, but similar investigations in males have remained scarce. To study if testis weight-a measure of reproductive investment-varies on a geographical scale in anurans, we focussed on the variation in relative testis weight (RelTW) and asymmetry in 22 populations of the common frog Rana temporaria along a 1,600-km latitudinal transect across the Scandinavian peninsula. We found that RelTW decreased towards the north. Body mass and body length both had independent positive effects on testes mass. We found evidence for directional asymmetry (DA) in testis weight with the right testis being larger than the left. The level of DA in testis weight was not related to latitude, but both body mass and testes mass had independent positive effects on asymmetry. We discuss the northwards decrease in RelTW in terms of a decreased reproductive investment as a possible consequence of harsher environmental conditions, and perhaps also, weaker sexual selection in the north than in the south.

Animals↗
PubMed2003

Androgen and oestrogen receptor status of the human appendix testis.

Since the human appendix testis is a Mullerian duct derivative it has been theorised that rising oestrogen levels in puberty result in enlargement of this organ and consequent predisposition to torsion. This study sought to establish the presence or absence of both androgen and oestrogen receptors in the human appendix testis. Bilateral appendix testis specimens surgically excised from ten patients undergoing scrotal exploration for acute scrotum were stained immunohistochemically for androgen and oestrogen receptors. These were examined by light microscopy. The human appendix testis was found to express both oestrogen and androgen receptors. Marked regional variation of androgen and oestrogen receptor positivity was demonstrated. The surface epithelium and some stromal cells were androgen receptor positive, whereas oestrogen receptors were confined to ductular invaginations, gland-like structures and some stromal cells. Rising levels of androgens and oestrogens in pubertal boys may account for enlargement and the predisposition of the human appendix testis for torsion since this structure contains receptors for both.

Adolescent↗
PubMed2001

The biological effect of phthalate esters on transabdominal migration of the testis in fetal rats in comparison with the antiandrogen flutamide.

Phthalate esters are commonly used as plasticizers for polyvinyl chloride and are known to be hormone-disrupting chemicals. We previously reported that mono-n-butyl phthalate (MBP) administered to rat fetuses induced cryptorchidism postnatally. The aim of this study was to investigate the biological effect of MBP on the transabdominal migration of the testis in prenatal rats by comparing this with the prenatal effect of the antiandrogen flutamide on testicular descent. Time-pregnant Wistar King A rats were divided into three groups: group I rats (N = 3) were administered MBP 0.3 g/day by gavage from gestational days 15 to 18; group II rats (N = 3) were injected with flutamide (30 mg/day) from gestational days 15 to 18; group III rats (N = 3) were administered solvent as controls. On the 19th gestational day, all rats underwent a cesarean section and the male fetuses were dissected to examine the position of the testis, which was significantly higher in the abdominal cavity in the MBP-treated rats than in either the flutamide-treated or control rats. No significant difference was observed in the position of the testis between the flutamide-treated and control rat fetuses. Our findings suggest that maternal MBP prevented transabdominal migration of the testis in prenatal rats, which may not have been due to either an antiandrogenic or estrogenic effect of MBP, but to a direct toxic effect of MBP on the testis.

Animals↗
PubMed2001

Evaluation of developing rat testis by phosporus 31P magnetic resonance spectroscopy and DNA flowcytometry.

For the assessment of germ-cell maturation of the seminiferous tubules, DNA flowcytometry is a rapid and sensitive method. Phosporus 31P magnetic resonance spectroscopy (MRS) is a non-invasive alternative that demonstrates the metabolic status of the testis, reflecting the type and relative proportion of germ cells in the testis. This study was designed to evaluate the utility of 31P MRS in reflecting the haploid-cell population of the testis as measured by DNA flowcytometry. A single testicle was evaluated in male Wistar pre-pubertal rats at 30, 40, 50, and 60 days of age. In order to minimize the contamination of signals from the contralateral testis, scrotum, and tail, the technique was modified and the testis was evaluated ex-vivo with an intact blood supply. At 30 days of age the percentage of haploid cells was 43.6 +/- 1.8, and this increased to 72.7 +/- 1.4 at 60 days of age. During this period, the testicular phosphomonoester/adenosine triphosphate (PM/ATP) ratio changed from 1.70 +/- 0.21 to 0.32 +/- 0.08. There was a significant (P < 0.001) linear correlation between the proportion of haploid cells evaluated by DNA flowcytometry and the PM/ATP ratio evaluated by 31P MRS. 31P MRS is thus a reliable, noninvasive technique for accurately assessing the status of the seminiferous epithelium.

Animals↗
PubMed2003

The so-called "testis-specific aldehyde dehydrogenase" corresponds to type 2 retinaldehyde dehydrogenase in the mouse.

The distribution pattern of "testis-specific aldehyde dehydrogenase" in mouse tissues was investigated. Because of the broad substrate specificity and the high degree of sequence identity of the large aldehyde dehydrogenase family a specific detection of single isoforms is not possible by histochemical means. Therefore, the technique of native isoelectric focusing was used. Thus, the expression of four to five banded "testis-specific aldehyde dehydrogenase" in the mouse testis was confirmed. However, the activity of this enzyme with the same pattern of multiplicity was found not only in the testis but also in the uterus and in embryonic tissues. At 9.5 and 10.5 days of embryonic development the enzyme activity was restricted to tissues of the embryonic trunk and absent in extracts from cranial tissues. The tissue distribution as well as substrate specificity and isoelectric points indicate that the "testis-specific aldehyde dehydrogenase" corresponds to mouse type 2 retinaldehyde dehydrogenase.

Aldehyde Oxidoreductases↗
PubMed2006

Expression and distribution of trihydrophobin 1 in postnatal developing mouse testis.

The human trihydrophobin 1 (TH1) is a highly conserved and widely expressed protein. It is clear that TH1 serves as a new specific negative regulator of A-Raf kinase. In this study, we found that TH1 associated with A-Raf in mouse testis by using coimmunoprecipitation analysis. Then we characterized the gene expression of TH1 in mouse testis and analyzed the changes of TH1 protein during postnatal development. The protein expression of TH1 in mouse testis was further analyzed by immunohistochemistry staining. Strong signals were detected in the seminiferous tubules and the distribution patterns varied with the different ages of postnatal mouse testis. TH1 was distributed in spermatocytes and Sertoli cells at 2 weeks postnatal, and was abundant in spermatogonia at 8 weeks postnatal. Leydig cells were positive to TH1 throughout testicular development. A high expression of TH1 in both Leydig cells and mouse Leydig tumor cells (mLTC-1cells) was found to be concentrated in the cytoplasm. The colocalization of TH1 and A-Raf in mLTC-1 cells or in adult testis was also observable.

Animals↗