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PubMed2000

Induction of metallothionein synthesis with preservation of testicular function in rats following long term renal transplantation.

Metallothionein (MT), as an acute phase or stress-response protein and free radical scavenger, is related to inflammation and cellular protection from oxidative damage. In order to evaluate long-term testicular damage and the role of MT following renal transplant, nine allogenic (Fisher 344 --> Lewis) and seven isogenic (Lewis --> Lewis) renal transplants were performed and the recipient rats were followed for 140 days when allografts develop chronic transplant rejection. Testicular weight, light microscopic morphology, and lactate dehydrogenase-X enzyme activity were assessed. Testicular MT was determined by Cd-heme assay, and was localized immunocytochemically using a polyclonal rabbit antibody. No differences in testis weight, morphology, or LDH-X enzyme activity were found between allograft and isograft recipients. Testicular MT level was significantly increased in the testis of allograft recipients. Testicular zinc (Zn) and copper (Cu) levels, but not iron (Fe) level, were significantly higher in testis with allograft kidney than that with isograft kidney. In addition, Cu/Zn ratio was also significantly high in the allograft group. However, the MT level did not show any significant correlation either with Cu and Zn alone or with Cu/Zn and Fe/Zn ratios. These data suggest that allogenic stimuli may induce MT synthesis in the recipient testis. The increased MT level in an allograft may offer a protective action from oxidative damage in the testis.

Animals↗
PubMed2003

Sexual development and the effects of active immunization against GnRH in Chinese Tanyang ram lambs.

Tanyang is one of the most important sheep breeds in the northwest of China. However, there is no detailed data on sexual development and timing of puberty/sexual maturity of this breed. This experiment was designed to study the relationships between growth rate and sexual development by measuring body weight, testis diameter, and plasma testosterone concentrations, and observing sexual behavior through puberty from 3 to 8 months old of entire Tanyang ram lambs. At same time, to assess the potential efficacy and welfare benefits of non-surgical castration, the effect of active immunization against gonadotrophin-releasing hormone (GnRH) on sexual development and growth rate on ram lambs was evaluated, and compared with surgically castrated and entire lambs. The results showed that body weight increased at a constant rate from 3 to 8 months old of age. Testis diameter increased rapidly between 3 and 5 months, followed by a period of slow growth. Plasma testosterone concentrations increased sharply from 3 to 6 months of age (P<0.05), after which there were no significant changes from 6 to 8 months of age. Sexual behavior started from 5 months of age. After ram lambs were immunized against GnRH at 3 months of age, there was no increase in testis diameter in the first 4 months after immunization. Plasma testosterone concentrations remained at similar levels to surgically castrated lambs until 6 months of age, and the onset of sexual behavior was delayed, compared with entire ram lambs. GnRH immunization and surgical castration had no significant effect on the body weight by the end of this experiment. These results suggest that 4-5 months of age is a critical period for pubertal changes and testosterone plays an important role in the initiation of puberty and sexual maturity of Tanyang ram lambs in China. In addition, a single shot GnRH immunization at 3 months, acting as an alternative to surgical castration, is a practical method for Chinese Tanyang ram lambs, and provides animal welfare benefits.

Aging↗
PubMedDate not supplied

Effect of the anti-androgenic endocrine disruptor vinclozolin on embryonic testis cord formation and postnatal testis development and function.

Vinclozolin is a systemic dicarboximide fungicide that is used on fruits, vegetables, ornamental plants, and turf grass. Vinclozolin and its metabolites are known to be endocrine disruptors and act as androgen receptor antagonists. The hypothesis tested in the current study is that transient embryonic exposure to an anti-androgenic endocrine disruptor at the time of testis determination alters testis development and subsequently influences adult spermatogenic capacity and male reproduction. The effects of vinclozolin on embryonic testicular cord formation in vitro were examined, as well as the effects of transient in utero vinclozolin exposure on postnatal testis development and function. Embryonic day 13 (E13, sperm-positive vaginal smear day = E0) gonads were cultured in the absence or presence of vinclozolin (50-500microM). Vinclozolin treated gonads had significantly fewer cords (P < 0.05) and the histology of the cords that formed were abnormal as compared to vehicle-treated organs. Pregnant rats were exposed to vinclozolin (100 mg/kg/day) between embryonic days 8 and 14 (E8-E14) of development. Testis morphology and function were analyzed from postnatal day (P) 0, pubertal P20, and adult P60. No significant effect of vinclozolin on testis histology or germ cell viability was observed in P0 testis. The pubertal P20 testis from vinclozolin exposed animals had significantly higher numbers of apoptotic germ cells (P < 0.01), but testis weight was not affected. The adult P60 sperm motility was significantly lower in vinclozolin exposed males (P < 0.01). In addition, apoptotic germ cell number in testis of vinclozolin exposed animals was higher in adult P60 animals. Observations demonstrate that vinclozolin can effect embryonic testicular cord formation in vitro and that transient in utero exposure to vinclozolin increases apoptotic germ cell numbers in the testis of pubertal and adult animals. This correlated to reduced sperm motility in the adult. In conclusion, transient exposure to vinclozolin during the time of testis differentiation (i.e. cord formation) alters testis development and function. Observations indicate that transient exposure to an anti-androgenic endocrine disruptor during embryonic development causes delayed effects later in adult life on spermatogenic capacity.

Androgen Antagonists↗
PubMed1991

Does unilateral orchidectomy influence blood flow, microcirculation and vascular morphology in the remaining testis?

Adult rats were hemi-orchidectomized and various aspects of testicular blood flow, microcirculation and vascular morphology were studied in the remaining testis after 30 days and compared to that in intact sham-operated animals. Testis weight, total testicular blood flow (measured with microspheres), capillary blood flow pattern (studied with laser Doppler flowmetry) and the volume of interstitial fluid in the testis (index of vascular permeability) were all unaffected by hemi-orchidectomy. Morphometric measurements on perfusion-fixed testicular tissue showed that the volume densities of Leydig cells, blood vessels and small exchange blood vessels were increased by hemi-orchidectomy (by approximately 45, 33 and 42%, respectively). The volume density of Leydig cells in individual testes was correlated to the volume and surface density of capillaries + small postcapillary velules (r = 0.72 and 0.86, respectively). Hemi-orchidectomy is known to result in a doubling in testosterone secretion per Leydig cell. This increased endocrine activity results in moderate increase in the vascular exchange area but other aspects of testicular microcirculation and blood flow are apparently unaffected.

Animals↗
PubMed1978

Effects of pipecolinomethylhydroxyindane on testicular and adrenocortical function in rats.

Mature and young adult rats were treated with a single dose of 115 mg and 50 mg of pipecolinomethylhydroxyindane (PMHI) maleate per kg of body weight. Large intraperitoneal doses were toxic in mature rats and the growth of younger animals were retarded by the lower subcutaneous dose. In both instances, PMHI caused a rapid reduction in testis weight with arrested spermatogenesis. Atrophic changes to the ventral prostrate and the lowering of blood testosterone levels suggests that the actions of PMHI are not strictly confined to the seminiferous tubules. This was further substantiated by the demonstration of direct inhibition by PMHI of testicular androgenesis in vitro. The actions of PMHI on steroidogenesis may be readily reversible and, compared to tubular actions, are of a minor nature. There were no clear-cut adrenocortical responses to PMHI administration but there was some depression of adrenal gland weight, plasma corticosterone, and aldosterone.

Adrenal Cortex↗
PubMed1984

Effects of 1,2-dibromo-3-chloropropane on male reproductive function in the rat.

The pesticide 1,2-dibromo-3-chloropropane (DBCP) is a known male reproductive toxin. Previous studies employed production-grade DBCP containing allyl chloride and epichlorohydrin, both capable of producing effects similar to DBCP. The purpose of this study was to determine if purified DBCP caused the same effects as DBCP containing allyl chloride. Rats were injected for 6 mo with varying doses of pure or production-grade DBCP. Very few differences were observed in the parameters measured between pure and production-grade DBCP-treated animals at any one dose level. Treatment with 25 mg/kg DBCP, pure or production grade, reduced body weight as well as the weight of the testes, prostate glands and seminal vesicles, and elevated serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This dose of pure DBCP reduced serum testosterone. Treatment with 5 mg/kg of either grade DBCP caused decreases only in body and testis weights. Animals treated with 1 mg/kg did not show any major differences from controls. These results indicate that DBCP, and probably not a contaminant, is responsible for the effects observed on male reproduction. Furthermore, DBCP appears to affect either androgen action or production since multiple androgenic indices are affected by DBCP administration.

Animals↗
PubMed2006

Gene expression profiling in liver and testis of rats to characterize the toxicity of triazole fungicides.

Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected for hormone measurements, and liver and testes were collected for histology, enzyme biochemistry, or gene expression profiling. Body and testis weights were unaffected, but liver weights were significantly increased by all four triazoles, and hepatocytes exhibited centrilobular hypertrophy. Myclobutanil exposure increased serum testosterone and decreased sperm motility, but no treatment-related testis histopathology was observed. We hypothesized that gene expression profiles would identify potential mechanisms of toxicity and used DNA microarrays and quantitative real-time PCR (qPCR) to generate profiles. Triazole fungicides are designed to inhibit fungal cytochrome P450 (CYP) 51 enzyme but can also modulate the expression and function of mammalian CYP genes and enzymes. Triazoles affected the expression of numerous CYP genes in rat liver and testis, including multiple Cyp2c and Cyp3a isoforms as well as other xenobiotic metabolizing enzyme (XME) and transporter genes. For some genes, such as Ces2 and Udpgtr2, all four triazoles had similar effects on expression, suggesting possible common mechanisms of action. Many of these CYP, XME and transporter genes are regulated by xeno-sensing nuclear receptors, and hierarchical clustering of CAR/PXR-regulated genes demonstrated the similarities of toxicogenomic responses in liver between all four triazoles and in testis between myclobutanil and triadimefon. Triazoles also affected expression of multiple genes involved in steroid hormone metabolism in the two tissues. Thus, gene expression profiles helped identify possible toxicological mechanisms of the triazole fungicides.

Animals↗
PubMed1988

Association of sperm, vaginal cytology, and reproductive organ weight data with results of continuous breeding reproduction studies in Swiss (CD-1) mice.

In continuous breeding reproduction studies in which an adverse effect on fertility was detected over an 18-week treatment period, a crossover mating trial was then conducted to determine the affected sex. Results of 25 crossover breeding studies conducted using Swiss (CD-1) mice were compared with results of sperm morphology and vaginal cytology examinations (SMVCEs) conducted at the conclusion of the mating trial. SMVCE endpoints include sperm concentration, motility, and morphology, vaginal cytology, and male reproductive organ weights. In most SMVCE studies multiple endpoints were adversely affected. For male reproductive toxicants, sperm motility was decreased in 89% of the studies, and absolute right epididymis and right testis weights were affected less frequently (80% each). Among studies with no detectable reduction in male breeding performance, 87% exhibited no detectable decrease in epididymis weight. Eighty-two percent had no change in cauda epididymis weight and 80% had no significant change in sperm concentration. An increase in female cycle length was associated (100%) with an effect on breeding due to female dysfunction. Overall accuracy, defined as correct identification of toxicants and nontoxicants, was highest for epididymis weight (84%), followed by cauda epididymis weight and sperm motility (79% each), and sperm concentration (76%). Female cycle length was so variable that the overall accuracy of the parameter in 13 studies was 69%. With the variety of chemicals used in this analysis, the association of abnormal sperm morphology with reproductive outcome was 71%. Control data (mean, 95% confidence interval around the mean, median, and statistical sensitivity) for each male endpoint (parent, and offspring at 10 weeks of age following a single breeding) were summarized from each of the two laboratories that conducted the studies. For several endpoints, statistical power was dependent on the laboratory conducting the studies. In general, the statistical sensitivity was relatively high for reproductive organ weights, although it was less for smaller organs such as the prostate. On the basis of both the biological and statistical analyses, it is recommended that multiple SMVCE endpoints, including sperm measures, be included in screens for reproductive toxicants.

Animals↗
PubMed1973

Permeability of Sertoli cell tight junctions to lanthanum after ligation of ductus deferens and ductuli efferentes.

The permeability of Sertoli cell tight junctions to lanthanum administered during fixation has been compared in rats after ligation of the ductus deferens and after ligation of the ductuli efferentes. In both control and vasoligated testes, lanthanum penetrated only short distances into the Sertoli cell tight junctions before stopping abruptly. The tight junction, consisting of numerous pentalaminar fusions of contiguous Sertoli cell membranes, prevented diffusion of lanthanum into the adluminal compartment of the seminiferous epithelium. In rats with ligated ductuli efferentes, lanthanum completely permeated many Sertoli cell tight junctions and occupied intercellular spaces of the adluminal compartment. In spite of their newly acquired permeability to lanthanum, tight junctions retained characteristic ultrastructural features, including numerous membrane fusions. When lanthanum-filled tight junctions were sectioned en face, membrane fusions appeared as pale lines in lakes of electron-opaque tracer. These linearly extensive fasciae occludentes occasionally ended blindly, suggesting that lanthanum may have traversed the junction by diffusing around such incomplete barriers. The increased permeability of Sertoli cell tight junctions after efferent ductule ligation, which caused rapid testicular weight gain followed by atrophy, indicates that tight junctions are sensitive to enforced retention of testicular secretions inside the seminiferous tubules. The apparent normalcy of Sertoli cell tight junctions after vasoligation, which had no effect on testis weight, supports the view that blockage of testicular secretions distal to the epididymis is relatively innocuous.

Animals↗
PubMed1989

Cytotoxic effects of benzene on mouse germ cells determined by flow cytometry.

Flow cytometric (FCM) DNA content measurements were performed on testicular monocellular suspensions obtained from mice exposed per os to 0, 1, 2, 4, 6, and 7 ml/kg body weight of benzene in order to investigate its cytotoxic action on germ cells. The effects of benzene were measured 7, 14, 21, 28, and 70 d after treatment. Benzene had no effect on testis weight, but FCM analysis showed the relative percentages of some cell subpopulations (tetraploid and haploid cells) to be different from the control pattern, indicating the occurrence of some cytotoxic damage to differentiating spermatogonia. These data demonstrate that spermatogenesis is sensitive to benzene single exposures as evidenced by an altered cell ratio of testicular cell types.

Animals↗
PubMed2002

Testicular zinc, copper and iron concentrations in male rats exposed to subacute and subchronic formaldehyde gas inhalation.

The level of trace elements such as Zn, Cu and Fe in testicular tissue is an indication of the condition of the tissue as these elements take over important tasks. Zinc and copper are the prosthetic groups of several metalloenzymes including superoxide dismutase (SOD) which is an important antioxidant enzyme in the cellular protection from reactive oxygen species. If concentrations of these trace elements decrease significantly, SOD cannot detoxify harmful oxygen species. In this study, adult male rats (wistar-albino) were exposed to formaldehyde at different periods (subacute and subchronic) and concentrations (0; 12.2; 24.4 mg.L-1). Body and testis weights were recorded and compared with control groups. The metals described above were determined in rat testicular tissue by atomic absorption spectrometry by using wet ashing. We conclude that subacute or subchronic exposure to formaldehyde have caused growth retardation and altered levels of trace elements, including copper, zinc and iron, in testicular tissue, and may induce further oxidative damage on testicular tissue leading to spermatozoal abnormalities.

Animals↗
PubMed2000

Seasonal variations in daily sperm production rate of rhesus and bonnet monkeys.

Daily sperm production (DSP) rate was estimated in adult male rhesus and bonnet monkeys to evaluate seasonal changes in the gametogenic activity of the testes. Three monkeys of each species were castrated during breeding and non-breeding seasons and DSP rate was estimated by enumerating the homogenization-resistant spermatid nuclei of steps 13 and 14. Results indicated a significant reduction in the DSP rate per testis during the non-breeding season in two species, along with a marked decline in the testis weight. However, the gametogenic capacity of seminiferous tubules did not appear to be markedly affected during non-breeding season, as the DSP rate per gram parenchyma of testis was only marginally reduced. The seasonal changes in DSP were much more pronounced in the rhesus than in the bonnet monkey. The feasibility of circanual rhythm in DSP of sub-human primates to form a baseline for the study of reproductive function in male is discussed.

Animals↗
PubMed1979

Long-term estrogenization in mammals. I. Histopathology of kidney, bladder, adrenals, and gonads; polydipsia; body weight; and serum levels of corticosterone and testosterone in estrogenized Marsh mice.

Single, sublethal, long-acting doses of estrone or estradiol cypionate produced the following histologic, behavioral, and blood chemistry effects in Marsh mice: (a) Bladder pathology developed following estrogen-induced polydipsia but was not consistently associated with kidney damage. (b) This polydipsia was more intense (a maximum of 250% over control intake) when the housing was in metal cages with floor screens than in plastic cages with bedding. Water intake of control mice was unaffected by housing changes. (c) Comparing litter-mate 2.5-month-old males and females, body weight loss following estrogen administration was transient with the females. With males, initial weight losses as compared with weight gains in the controls were demonstrated over a 20-week period. (d) Estrogenization markedly increased corticosterone and decreased testosterone serum levels with a significant negative correlation for these levels in the estrogenized mice. A significant positive correlation was also observed between testosterone levels and testis weights in the estrogenized mice.

Adrenal Glands↗
PubMedDate not supplied

Perinatal fenvalerate exposure: behavioral and endocrinology changes in male rats.

The effects of maternal exposure to fenvalerate during the prenatal and postnatal periods of sexual brain differentiation were studied in adult male offspring. Behavioral (open field, stereotyped, and sexual behaviors), physical (sexual maturation, body and organ weights), endocrine (testosterone levels), and neurochemical (striatal and hypothalamic monoamine and respective metabolite levels) data were assessed. The results showed that there was no change in the age of testis descent or testis weight, nor were there changes in monoamine levels or stereotyped behavior. However, there were significant reductions in ductus deferens and seminal vesicle weights and plasma testosterone concentrations. In addition, treated offspring showed decreased male sexual behavior and increased immobility in the open field. These results indicate that perinatal exposure to fenvalerate during the critical periods of male brain sexual differentiation has long-term effects on the reproductive physiology and behavior of male rats.

Animals↗
PubMed1990

Influence of hypothyroidism on in-vitro testicular steroidogenesis in adult rats.

The influence of hypothyroidism on testicular steroidogenesis was investigated by evaluating the production of testosterone and its precursors by isolated testes from adult male rats. Animals were made hypothyroid starting from the 4th week of life either by daily oral administration of 0.1% methimazole (MMI) or by surgical thyroidectomy (TZ). Half of the thyroidectomized rats were i.p. injected with 3 gamma T3/100 g body weight on alternate days during the last three weeks before sacrifice. Hypothyroidism is associated with a severe retardation of body growth, which appears more marked in thyroidectomized than in MMI treated rats; no significant variations in testis weight are observed. Administration of T3 does not completely restore body weight. A significant decrease in the "in vitro" production of testosterone and its precursors by testes isolated from hypothyroid rats is observed. This effect is more evident in thyroidectomized rats where a marked drop in the "in vitro" production of some testosterone delta 4 precursors is associated with the increase in DHEA/delta 4 ratio. T3 injection to thyroidectomized rats only partially restores the "in vitro" testosterone production. Results suggest that as the degree of hypothyroidism became more severe, the rate of testosterone production decreases and testicular steroidogenesis changes from the delta 4 to delta 5 metabolic pathway as a consequence of the impairement of 3-beta-ol-dehydrogenase activity.

Androstenedione↗
PubMed1988

Evaluation of spermatogenesis and sperm quality in the rat following acute inhalation exposure to methyl bromide.

Methyl chloride (MeCl) and methyl bromide (MeBr) have similar target organ specificities in the male F-344 rat, and MeCl is a known reproductive toxicant in that species. Recently, both acute and subchronic inhalation exposures to MeBr were found to produce varying degrees of testicular alteration (S.L. Eustis, S.B. Haber, R.T. Drew, and R.S.H. Yang, 1986, Toxicologist, 6, 54; N. Kato, S. Morinobu, and S. Ishizu, 1986, Ind. Health, 24, 87-103; M.E. Hurtt, K.T. Morgan, and P.K. Working, 1987, Fundam. Appl. Toxicol., 9, 352-365). The present study examined the reproductive effects of MeBr in the male F-344 rat. Adult males (11-13 weeks) were exposed by inhalation to 0 or 200 ppm MeBr 6 hr/day for 5 days (first day of exposure = Day 1). Ten animals from each group were anesthetized with pentobarbital and terminated on Days 1, 3, 5, and 8. Additionally, five males from each group were killed on Days 6, 10, 17, 24, 38, 52, and 73. Plasma testosterone concentration was reduced during and immediately following exposure (Days 1, 3, 5, and 6), but returned to control levels by Day 8. Nonprotein sulfhydryl (NPSH) content of the liver and testis was reduced during exposure but returned to control levels by Day 8 (3 days postexposure). No other reproductive indices, including testis weight, daily sperm production, cauda epididymal sperm count, sperm morphology, percentage motile sperm, linear sperm velocity, and epididymal and testicular histology, were affected by MeBr exposure at any time point examined. Thus, although MeBr causes a transient decrease in plasma testosterone and testicular NPSH concentrations during acute exposure, it has no lasting effect on sperm quality or spermatogenesis in the F-344 rat.

Administration, Inhalation↗
PubMed2004

Effects of acute postnatal exposure to 3,3',4,4'-tetrachlorobiphenyl on sperm function and hormone levels in adult rats.

Polychlorinated biphenyls (PCBs) are considered potential endocrine disruptors due to their ability to act as estrogens, antiestrogens and goitrogens. The aim of this study is to ascertain whether acute postnatal treatment with 3,3',4,4'-tetrachlorobiphenyl (CB 77) affects sperm function and hormone levels in adult rats. Male Sprague-Dawley rats received CB 77 by ip injection of 2 or 20 mg/kg at day 21 and sacrificed at day 112. At day 112, right and left testis weights were significantly increased, whereas sperm count, motility, total motile sperm count, curvilinear velocity, average path velocity, straight-line velocity, and beat-cross frequency for motile sperm were significantly decreased in rats treated with 20 mg/kg CB 77. Sperm-oocyte penetration rate was significantly reduced in rats treated with either 2 or 20 mg/kg CB 77. There was high sperm acrosome reaction rate (ARR) in the 20 mg/kg CB 77-treated rats. There was a significant increase in thyroid-stimulating hormone level in the 20 mg/kg CB 77 group. However, no changes were seen in serum testosterone, thyroid hormones, or prolactin concentrations at day 112. In summary, this study showed that postnatal exposure to CB 77 might affect spermatogenesis, motility, ARR, and ability of fertilizing oocytes in mature rats. These results suggest that the sperm functions may be more susceptible or adapt less readily than the thyroid functions to endocrine disruption caused by dioxin-like PCB congeners.

Analysis of Variance↗
PubMed1986

Effect of protein malnutrition on glycoprotein synthesis by testes of 20-day-old rats.

The effects of protein malnutrition during the nursing period on glycoprotein biosynthesis by testes of 20-day-old rats was studied. Pregnant Wistar rats were housed individually. On the day of delivery they were divided into two groups: one was fed a control diet (25% casein) and the other a low-protein diet (8% casein) for a period of 20 days. Body and testis weights of pups suckled by the malnourished mothers were significantly lower than those of the pups suckled by normally-fed mothers. The seminiferous tubules o malnourished rats showed a significant decrease in diameter and in the stage of development of spermatogenesis. Whole testes of normally-fed 20-day-old rats showed significantly greater [2-3H]mannose incorporation into glycoproteins than did the testes of malnourished rats of the same age. The microsomes of normally-fed rats showed significantly higher GDP: mannose polyprenyl mannosyl transferase activity than did microsomes from malnourished rats, and this difference increased when exogenous dolichyl-phosphate was added to the incubation medium. These results indicate that protein malnutrition decreases GDP: mannose polyprenyl mannosyl transferase activity in the microsomes of testes from 20-day-old rats.

Animals↗