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PubMed2006

Disruption of testosterone homeostasis as a mode of action for the reproductive toxicity of triazole fungicides in the male rat.

Triazole fungicides associated with a range of reported male reproductive effects in experimental animals were selected to assess potential toxic modes of action. Wistar Han rats were fed myclobutanil (M: 100, 500, or 2000 ppm), propiconazole (P: 100, 500, or 2500 ppm), or triadimefon (T: 100, 500, or 1800 ppm) from gestation day 6 to postnatal day (PND) 120. One male per litter was necropsied on PND1, 22, 50, or 92. Measurements included anogenital distance (AGD) at PND0, body and organ weights, serum hormone levels, age at preputial separation (PPS), sperm morphology and motility, and fertility and fecundity. AGD was increased by the high dose of all three triazoles, indicating hypervirilization. Triadimefon delayed PPS, consistent with delayed puberty, at 1800 ppm. Relative liver weights were increased at PND1, 50, and 92 by all three triazoles. Hepatocellular hypertrophy was present at PND50 from propiconazole and triadimefon and at PND92 from all three high-dose triazole treatments. Relative pituitary weights were decreased at PND92 by middle- and high-dose myclobutanil treatment. Absolute testis weights were increased at PND1 by myclobutanil, at PND22 by myclobutanil and triadimefon, and at PND50 by propiconazole and triadimefon treatment. Relative ventral prostate weights were increased at PND92 by myclobutanil and triadimefon treatment. Serum testosterone was increased at PND50 by triadimefon and at PND92/99 by all three triazole treatments. Insemination and fertility were impaired by myclobutanil and triadimefon treatment. In addition to the reproductive system effects, total serum thyroxine levels were decreased at PND92 by high-dose triadimefon. These reproductive effects are consistent with the disruption of testosterone homeostasis as a key event in the mode of action for triazole-induced reproductive toxicity.

Anal Canal↗
PubMed2004

A variant of porcine thyroxine-binding globulin has reduced affinity for thyroxine and is associated with testis size.

The field of genomics applies the dissection of genetic differences toward an understanding of the biology of complex traits. Quantitative trait loci (QTL) for testis size, plasma FSH in boars, and body composition (backfat) have been identified near the centromere on the X chromosome in a Meishan-White Composite resource population. Since thyroid function affects Sertoli cell development and adult testis size in rodents, and thyroxine-binding globulin (TBG) maps to this region on the porcine X chromosome, TBG was a positional candidate gene for testis size. We discovered a polymorphism in exon 2 of the porcine TBG gene that results in an amino acid change of the consensus histidine to an asparagine. This single nucleotide polymorphism (SNP) resides in the ligand-binding domain of the mature polypeptide, and the Meishan allele is the conserved allele found in human, bovine, sheep, and rodent TBG. Binding studies indicate altered binding characteristics of the allelic variants of TBG with the asparagine (White Composite) isoform having significantly greater affinity for thyroxine than the histidine (Meishan) isoform. Alternate alleles in boars from the resource population are also significantly associated with testis weight. Therefore, this polymorphism in TBG is a candidate for the causative variation affecting testis size in boars.

Amino Acid Sequence↗
PubMedDate not supplied

DES induced sperm destruction in Lakeview hamsters.

DES toxicity on sperm production after five consecutive sublethal i.p. injections of 8, 40 and 200 mg/kg was investigated in Lakeview hamsters. Testis weight, caudal sperm number, sperm morphology and body weight were monitored at week 1, 4 and 10 after treatment. DES doses of 8 mg/kg or above caused complete destruction of caudal sperm and reduced testes size to almost 10% of control within 10 weeks. Some sperm production resumed after the 8 mg/kg dose at the 10th week but more than half of these cells were abnormal in shape. Body weights remained almost stable for the first 4 weeks and then increased gradually by 25% at the 10th week.

Animals↗
PubMed1990

Comparisons of endocrinological and testis parameters in 18-month-old Ile de France and Romanov rams.

Endocrinological and testis parameters of adult 18-month-old Ile de France (IF) and Romanov (Ro) rams were compared during sexual season. Testis weights, total volumes of intertubular tissue, and of blood and lymph vessels, total seminiferous tubule length, rete testis flow rate and daily production of germ cells were significantly higher in IF than in Ro rams. These variations originated from differences in Sertoli cell numbers, which were established before puberty. When daily productions of germ cells, of ABP or of RTF were expressed per Sertoli cell, they were higher in Ro than in IF rams. Quality of spermatids, as measured by their cellular size prior to elongation, was lower in Ro than in IF. The number of FSH-binding sites per Sertoli did not differ between the two breeds but FSH plasma levels were higher in Ro than in IF rams. Total numbers of Leydig cells per testis, their individual size or their LH-binding capacity did not differ significantly between the two breeds. However, the ratio of mean testosterone upon mean LH plasma levels were greater in Ro than in IF rams while both breeds had identical LH mean plasma levels.

Animals↗
PubMedDate not supplied

An ecotoxicological study of a population of the white footed mouse (Peromyscus leucopus) inhabiting a polychlorinated biphenyls-contaminated area.

White footed mice (Peromyscus leucopus) inhabiting an area surrounding a pond (Tyler) contaminated with polychlorinated biphenyls (PCBs) and metals (Cadmium, Zinc, Copper) had whole body burdens of 0.42-4.17 ppm PCBs (mean 2.3 ppm) and animals from a comparison nonpolluted site (WCC) had no detectable PCBs. Males and females caught at the polluted site in the winter months were not significantly different in body weight or length when compared to WCC animals, but Tyler animals had significantly increased relative liver, kidney, spleen and adrenal weights. In the summer months, mostly males were caught at both Tyler and WCC sites. Tyler males were significantly lighter than WCC males, and had a significantly increased relative liver weight when compared to the males from the WCC site. In addition, the adult Tyler males had significantly lower relative testis weights. At Tyler there was a significantly smaller proportion of juveniles and subadults in the population than at WCC. Polychlorinated biphenyls levels in the adult Tyler males were significantly positively correlated with relative liver weight, but there were no significant correlations with any of the other structures measured. These results suggest that at the polluted site there is inhibition of reproduction and changes in liver, spleen, adrenal, and testis function.

Animals↗
PubMed2005

Effect of chronic ethanol administration on testicular antioxidant system and steroidogenic enzyme activity in rats.

In order to find out the effect of chronic ethanol administration on testicular antioxidant system and steroidogenic enzyme activity, male rats fed with ethanol 1.6g/kg body weight per day for four weeks were studied. Besides a drastic reduction in body and testis weight, there was decrease in ascorbic acid, reduced glutathione and activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in the testicular tissue of the treated animals. Simultaneously, there was increase in lipid peroxidation and glutathione S-transferase activity. Activities of 3 beta-hydroxy steroid dehydrogenase and 17 beta-hydroxy steroid dehydrogenase were also found decreased in the treated animals. The results indicate that chronic ethanol administration resulted in increase in oxidative stress and decrease in the activities of steroidogenic enzymes in the rat testes.

17-Hydroxysteroid Dehydrogenases↗
PubMed1987

2,5-Hexanedione alters microtubule assembly. I. Testicular atrophy, not nervous system toxicity, correlates with enhanced tubulin polymerization.

Charles River CD rats (200 g) were divided into three groups receiving either 1% 2,5-hexanedione (2,5-HD) or 0.035% 3,4-dimethyl-2,5-hexanedione (DMHD) in the drinking water or water alone (control) for 4 weeks. The two treated groups experienced similar nervous system dysfunction and systemic toxicity. Testicular toxicity, as evidenced by histological changes and decreased testis weight, was present only in 2,5-HD-treated rats. Tubulin was purified from brain and testis and assembly properties were determined. Purified brain and testis tubulin derived from the 2,5-HD-intoxicated rats displayed altered assembly with a shortened nucleation phase and more rapid rate of elongation. Brain tubulin from DMHD-intoxicated rats displayed assembly behavior similar to controls, while testis tubulin from DMHD-intoxicated rats displayed assembly behavior intermediate between the control and 2,5-HD tubulin preparations. The presence of gamma-diketone-induced assembly alterations following in vivo intoxication was accompanied by the formation of a high-molecular-weight protein identified as crosslinked tubulin. From these data, we conclude that microtubule assembly alterations are not etiologic in the development of nervous system dysfunction following intoxication but may represent the biochemical mechanism of 2,5-HD-induced testicular atrophy.

Animals↗
PubMed1998

The Parkes Lecture. Heat and the testis.

The evidence for the lower temperature of the testes of many mammals is summarized, and the reasons suggested for the descent of the testes into a scrotum are discussed. Descriptions are given of the various techniques used for studying the effects of heat on the testis, whole body heating, local heating of the testes (by inducing cryptorchidism, scrotal insulation or immersion of the scrotum in a water bath), and heating of tissue or cell preparations in vitro. The effects of heat are discussed, effects on the testis (weight, histology, physiology, biochemistry and endocrinology), on the numbers and motility of spermatozoa in rete testis fluid and semen, on fertilizing ability of spermatozoa and on the subsequent development of the embryos produced when spermatozoa from heated testes are used to fertilize normal ova. The possible mechanisms for the damaging effects of heat are discussed, as well as the importance of heat-induced abnormalities in male reproduction in domestic animals and humans.

Animals↗
PubMed2005

Effects of bisphenol A given neonatally on reproductive functions of male rats.

Male Sprague-Dawley rats (Crj:CD (IGS) were treated neonatally with bisphenol A (BPA) to evaluate effects on reproductive parameters. Animals were given BPA subcutaneously in corn oil to dosages of 0.002-97 mg/kg body weight, or 0.9 mg/kg 17beta-estradiol (E2) once a day from postnatal day (PND) 0 to PND 9. Preputial separation, copulatory rate, fertility rate, sperm analysis, serum testosterone levels, and gene expression in the testis were assessed. Males in the E2 group showed a decrease in testis weight and alterations of estrogen-mediated gene expression in the testis on PND 10, and by PND 150 incomplete preputial separation, decreases in the copulatory rate, testicular and accessory organ weights and number of sperm. In contrast, males in all BPA groups showed normal reproductive parameters. These results indicate that in male rats, BPA given during the neonatal period neither affected reproductive function nor evoked estrogen-mediated gene responses in the testis.

Animals↗
PubMed1988

Inhibition of testicular and somatic development after treatment of the postnatal rat with the Leydig cell cytotoxic ethylene dimethanesulphonate.

The Leydig cell cytotoxic ethylene dimethanesulphonate (EDS) was administered s.c. daily (50 mg/kg) to male rats aged 5-16 days. Apart from loss of weight and that the eyelids unfused earlier, no gross toxicity was observed during treatment. On day 17 testis weights, serum testosterone concentrations, testicular serum testosterone content and 125I-labelled human chorionic gonadotrophin (hCG) binding to testicular homogenates were reduced. Serum LH and FSH concentrations were elevated. The testes did not recover from EDS treatment and at 63 and 120 days were minute (less than 2% of control), and the prostate and seminal vesicles were small although not completely atrophied. In addition, body weights were substantially reduced. Serum and testicular testosterone and 125I-labelled hCG binding to testicular homogenates were reduced but not absent. Serum LH and FSH concentrations were increased. Light microscopy of the adult testes showed that EDS treatment inhibited the development of the seminiferous tubules. Most of the tubules were devoid of germ cells and Sertoli cells were rare. Occasionally tubules also contained spermatogonia and spermatocytes but no signs of spermiogenesis. The testes were composed mainly of closely packed interstitial tissue with no lymphatic space. The interstitial cells resembled Leydig cells and stained for 3 beta-hydroxysteroid dehydrogenase. Histochemically identified Leydig cells were absent during treatment but reappeared when treatment was withdrawn.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Effects of Butea superba on reproductive systems of rats.

The effects of Butea superba on the reproductive system in male Wistar rats were investigated. The animals were fed daily with the powdered crude drug suspended in distilled water by a gastric tube at the dose of 2, 25, 250 and 1250 mg/kg body weight for 8 weeks. Rats fed with 1 ml of distilled water were used as a negative control. The weights of all vital organs in all treated groups were not different from the control. The percentage weight ratios of body weights of seminal vesicles and prostate glands were not different from the control, except that the testis of the group fed with 1250 mg/kg was significantly different from the control and the other treated groups. In addition, the sperm counts in this group showed about 16% more than the control group. Hematology as well as the liver and kidney function of all treated groups showed no difference from the control. B. superba, drug at 250 mg/kg which was 100 times more than the Thai FDA recommended dose for humans appeared to be safe in rats. The crude drug has demonstrated an increase tendency on testis weight and sperm counts in rat. The information from the present study can be used to explain the Thai folklore application of this plant in Thailand.

Administration, Oral↗
PubMed2004

Effect of methoxychlor on various life stages of Xenopus laevis.

The toxicological effects of the organochlorine pesticide methoxychlor were evaluated at various life stages of the South African clawed frog, Xenopus laevis, in an effort to determine stage-specific sensitivity. A battery of four separate assays, including a short-term (4-day) early embryo-larval assay (FETAX) (NF stages 8-46 [Nieuwkoop and Faber, 1994]), 30-day hind limb development assay (NF stages 8-54), 18-day metamorphic climax assay (NF stages 58-66), and 30-day adult reproduction assay were performed. Test concentrations for the FETAX, hind limb development, metamorphic climax, and reproductive assays ranged from 0.0001-1.0 mg/l, 0.0001-0.1 mg/l, 0.0001-0.1 mg/l, and 0.001-0.1 mg/l, respectively. Results from the short-term embryo-larval assay indicated that increased embryo-lethality, malformation, and growth inhibition were not induced at </=1.0 mg/l methoxychlor (maximum soluble concentration). The 30-day hind limb development studies indicated methoxychlor exposure >/=0.01 mg/l delayed hind limb digit differentiation. Follicular hyperplasia of the thyroid glands was noted in specimens exposed to 0.1 mg/l methoxychlor. Results from the 18-day metamorphic climax assay indicated that methoxychlor inhibited the rate of tail resorption in a concentration-dependent manner. Whole body tissue triiodothyronine (T(3)) profiles showed a reduced and delayed surge during climax compared to controls. For the reproductive assessment, adult female X. laevis were super-ovulated and both female and male were then exposed to varying concentrations of methoxychlor. A concentration-dependent reduction in ovary weight and the number of viable oocytes was observed. In exposed male specimens, a concentration-dependent reduction in testis weight and sperm count was found. Methoxychlor was found to accumulate in the ovary, and to a lesser extent in the testis. Based on breeding studies in which exposed females were bred with control males and exposed males bred with control females, the frequency of amplexus, fertilization, and embryo viability was also affected by adult female methoxychlor exposure, and to a lesser extent by male exposure. Overall, these results suggested that sensitivity to methoxychlor is most dramatic during the reproductive and metamorphic phases of the life cycle and least sensitive during early embryo-larval development.

Animals↗
PubMed1988

Dissociated estradiol (E2) action on the pituitary-testicular axis in a genetically hypoprolactinemic rat (IPL nude rat).

Prolactin (PRL) has been reported to be a possible mediator in the estradiol (E2)-induced inhibition of the pituitary-testicular axis. In order to better characterize the role of PRL, we studied the action of chronic hypoprolactinemia on this E2 inhibitory effect, using a genetically hypoprolactinemic rat (IPL nude). Normal and IPL nude adult male rats were injected either with vehicle or with E2 valerianate (4 mg/rat) once a week for 2 weeks. Rats were decapitated 7 days after the last injection. Results showed that E2 increased, similarly in both strains, pituitary weight and serum PRL levels. Serum testosterone values were reduced by 96% in both strains. However, testis weight was significantly reduced by 30% in normal rat, while in IPL nude rat, no significant decrease was observed. PRL binding sites, expressed as fmol/mg protein, were reduced in normal rat by 40%. No decrease was found in IPL nude rat. The dissociated E2 action observed in IPL nude rat suggested that only testicular growth inhibition could be mediated by PRL and confirm that testosterone level decrease could be due to a direct action of E2 on Leydig cells.

Animals↗
PubMed2000

Effects of chronic dietary exposure to genistein, a phytoestrogen, during various stages of development on reproductive hormones and spermatogenesis in rats.

Developmental, hormonal, and gametogenic parameters were evaluated in male progeny following chronic dietary exposure to the phytoestrogen genistein. Twenty pregnant rats were fed a diet containing genistein (50 microg/d) from d 17 of gestation, and 12 were fed a control diet without genistein. Four litters each of control and genistein-fed rats were euthanized on d 21. The remaining pups were weaned on d 21 and only male rats were used in this study. On d 21, eight litters of genistein-fed rats were placed on control diet (gestational and lactational exposure alone [GL-G]), and the remaining eight continued on genistein diet (lifelong exposure group [LL-G]). These rats were euthanized (four litters/group) on d 70 or 130 of life. Serum testosterone, which was slightly reduced in genistein-exposed rats on d 21, did not differ among treatment and control groups on d 70 and 130. Serum luteinizing hormone of genistein-exposed rats was reduced on d 21 and 130, but not on d 70. Serum follicle-stimulating hormone did not vary among groups at any age. Treatment-related effects of dietary genistein were not observed on the weights of the testes of 21-d-old rats. Except for a slight decrease in testis weight of GL-G rats at 130 d, no significant effect of dietary exposure was observed on the weight of the testes in any other group. However, epididymal weights were significantly reduced in both treated groups at d 130. Testicular sperm count (on d 70 as well as 130) also was not affected in GL-G or LL-G rats. We conclude that gestational plus lactational exposure to genistein and subsequent dietary exposure to genistein have no adverse effects on gametogenic function in male rats.

Aging↗
PubMed2006

Infant feeding with soy formula milk: effects on puberty progression, reproductive function and testicular cell numbers in marmoset monkeys in adulthood.

BACKGROUND: This marmoset study addresses concerns about feeding human male infants with soy formula milk (SFM). METHODS: From age 4 to 5 days, seven male co-twin sets were fed standard formula milk (SMA) or SFM for 5-6 weeks; blood samples were subsequently collected at 10-week intervals. Testes from co-twins killed at 120-138 weeks were fixed for cell counts. RESULTS: SFM- and SMA-fed twins showed normal weight gain; puberty started and progressed normally, based on blood testosterone measurements. Body weight, organ weights (prostate, seminal vesicles, pituitary, thymus and spleen) and penis length were comparable in co-twins. All SMA- and 6/7 SFM-fed males were fertile. Unexpectedly, testis weight (P = 0.041), Sertoli (P = 0.025) and Leydig cell (P = 0.026) numbers per testis were consistently increased in SFM-fed co-twins; the increase in Leydig cell numbers was most marked in males with consistently low-normal testosterone levels. Seminiferous epithelium volume per tubule showed a less consistent, non-significant increase in SFM-fed males; raised germ cell numbers per testis, probably due to increased Sertoli cells, conceivably resulted in larger testes. Average lumen size, although greater in SFM-fed group, was inconsistent between co-twins and the difference was not significant. CONCLUSIONS: Infant feeding with SFM has no gross adverse reproductive effects in male marmosets, though it alters testis size and cell composition, and there is consistent, if indirect, evidence for possible 'compensated Leydig cell failure'. Similar and perhaps larger changes likely occur in adult men who were fed SFM as infants.

Animals↗
PubMed1993

Testicular weight, Sertoli cell number, daily sperm production, and sperm output of sexually mature rabbits after neonatal or prepubertal hemicastration.

The present study was conducted to investigate the influence of hemicastration and age at hemicastration on the subsequent testicular development of male rabbits through sexual maturity. Thirty New Zealand white rabbits were left intact or were hemicastrated on Day 35, 49, 77, or 105 postconception. Beginning at 7 mo of age, ejaculates were collected every other day for 1 mo, and the last ten ejaculates were used to quantify daily sperm output. At 8 mo, the rabbits were killed and their carcases, testes, testicular capsules, and epididymides were weighed. Testicular tissue was processed for quantification of sperm production rates by enumeration of homogenization-resistant spermatids and via histometric evaluation. Regardless of the age at hemicastration, this manipulation did not alter the development of the remaining testis as assessed from testis weight, numbers of Sertoli cells per testis, daily sperm production, or sperm output (p > 0.05). On the basis of these findings, it would appear that the development of the spermatogenic capacity of the remaining testis of the rabbit is not altered appreciably by hemicastration at a young age.

Animals↗
PubMed1996

[The effect of a low molecular weight synthetic humic substance on selected reproductive parameters of male rats].

Influences of the low molecular humic substance HS 1500 on parameters of organs (testis weight, epididymis weight), FSH-, and LH-levels in plasma as well as on the spermatogenesis of male rats were studied. After a daily oral application of 1000 mg/kg b.w. and 2000 mg/kg b.w., respectively over a period of 60 days (40th to 100th day of life) only 2 animals of the high dose group were observed with bilateral testicular atrophy. Despite of the two animals with testicular atrophy no significant differences between treated and control rats were observed with respect to testis morphology and spermatogenesis. There is no evidence whether the differences between the hormone levels and the testicular atrophy revealed is regarded to a HS 1500-effect or not. But otherwise a direct influence of HS 1500 can be ruled out with high certainty. Possibly because of the thin covering layer on the gastrointestinal mucous membrane formed by HS 1500, the absorption of nutritive substances is inhibited. Therefore the growth of sensitive organs like testis and epididymis, in the development period, can be decreased. Nevertheless, even after long time application the spermatogenesis is not influenced.

Administration, Oral↗
PubMed2003

Effect of neonatal treatment of rats with potent or weak (environmental) oestrogens, or with a GnRH antagonist, on Leydig cell development and function through puberty into adulthood.

This study addressed whether reduced Sertoli cell number or manipulation of the neonatal hormone environment has an influence on final Leydig cell number per testis in the rat, by applying neonatal treatments known to affect these parameters, namely administration of a GnRH antagonist (GnRHa) or diethylstilboestrol (DES, in doses of 10, 1 or 0.1 microg per injection). The effect of treatment with either of two 'environmental oestrogens', bisphenol-A (Bis-A) or octylphenol (OP), was also evaluated. Leydig (3beta-hydroxysteroid dehydrogenase immunopositive) cell development and function (plasma testosterone levels) were studied through puberty into adulthood. Treatment with GnRHa impaired testis growth, Leydig cell (nuclear) volume per testis and testosterone levels during puberty, when compared with controls, but final Leydig cell volume/number in adulthood was comparable with controls. As adult testis weight was reduced by 45% in GnRHa-treated rats, the percentage Leydig cell volume per testis was approximately double (p < 0.01) that in controls, and also at day 35. Testosterone levels in adulthood in GnRHa-treated rats were lower (p < 0.01) than in controls but were within the lower end of the normal range. Treatment with DES caused largely dose-dependent suppression of testis growth, Leydig cell (nuclear) volume per testis and testosterone levels up to day 35. Although by adulthood, Leydig cell volume/number per testis was comparable with controls in DES-treated rats, testosterone levels remained grossly subnormal. Neonatal treatment with either Bis-A or OP had little consistent effect on any of the parameters studied except that both treatments significantly elevated testosterone levels on day 18, as did treatment with DES-0.1 microg. The present findings are interpreted in the context of what is known about the hormonal regulation of Leydig cell development. These lead to the conclusion that final Leydig cell number per testis is not determined by the number of Sertoli cells per testis and appears not to be influenced in any major way by gonadotrophins, androgens or oestrogens in the first 2 weeks of postnatal life. This implies that adult Leydig cell number may be determined prior to birth.

3-Hydroxysteroid Dehydrogenases↗