Changes in testicular and serum hormone concentrations in the male rat following treatment with m-dinitrobenzene

m-Dinitrobenzene (m-DNB)-induced testicular atrophy has been attributed to a direct effect upon the germinal epithelium. However, such degenerative changes in the germinal epithelium should induce shifts in the testicular hormonal milieu, which would in turn alter the hypothalamic-pituitary gonadal axis in general. This study evaluated the endocrine status of male rats (killed 3 hr, 24 hr, 1 week, and 2 weeks) following a single oral dose of m-DNB (32 mg m-DNB/kg). Serum and pituitary leuteinizing hormone, follicle-stimulating hormone (FSH), and protactin and hypothalamic gonadotropin-releasing hormone (GnRH) concentrations were determined. Testosterone and androgen-binding protein concentrations in serum, interstitial fluid, seminiferous tubule fluid, and caput epididymis were also determined. In vitro basal and hCG-stimulated testosterone release was determined in the decapsulated testis. Results of the present study indicate that pituitary hormone concentrations and hypothalamic GnRH were unaffected after a single oral dose of m-DNB. Serum FSH was elevated at 2 weeks. There was a transient decrease in serum testosterone at 24 hr, which returned to control values at 1 and 2 weeks. Interstitial fluid, seminiferous tubule fluid, and caput epididymal testosterone concentrations were increased at 1 and 2 weeks. Basal testosterone release in vitro was increased at 2 weeks, while hCG-stimulated testosterone release was increased at 1 and 2 weeks. Androgen-binding protein concentrations in serum and interstitial fluid were increased at 1 and 2 weeks. Androgen-binding protein was increased at 24 hr and 1 week in seminiferous tubule fluid, but returned to control concentrations by 2 weeks. However, the total tubular content of androgen-binding protein was dramatically decreased at 2 weeks. Androgen-binding protein in the caput epididymis was unaltered following m-DNB treatment. These data demonstrate that m-DNB exerts a direct effect on the testes and not through alterations in hypothalamic and pituitary control of gonadal function.     

Changes in vascular dynamics of the adult rat testis leading to transient accumulation of seminiferous tubule fluid after administration of a novel 5-hydroxytryptamine (5-HT) agonist

The aim of the present study was to evaluate the possible mechanisms of testicular toxicity of GR40370X, a follow-up 5-hydroxytryptamine (5-HT) receptor agonist. Administration to adult male rats of a single (toxic) dose of 750 mg/kg GR40370X induced marked distension of seminiferous tubules and an associated increase in testis weight at 12-24 h with a gradual recovery to normal by 96 h. Seminiferous tubule distension was due to expansion of the lumen, which occurred at all stages of the spermatogenic cycle and was accompanied by vacuolation of the cytoplasm of elongating spermatids. Seminiferous tubule distension was preceded/accompanied by distension of the efferent ducts and rete testis with maximal changes evident at 24-48 h. These changes could not be explained by increases in seminiferous tubule fluid or interstitial fluid production, as both were reduced (15-20%), rather than increased, by treatment. Examination of the vasculature after treatment with 750 mg/kg GR40370X revealed significant changes that were maximal at 4 h and thus preceded rete/testicular changes. Veins of the mediastinal venous plexus, which overlies the rete, were constricted and arteriovenous anastomoses in the spermatic cord were shut/constricted, as determined (indirectly) by measurement of the dilution of outflowing testicular venous blood by incoming arterial blood. The latter effect of GR40370X could be blocked by co-administration of minoxidil, a vasodilator. Vascular effects of GR40370X had normalised by 24-48 h. It was also noted that administration of a toxic dose of GR40370X significantly lowered blood levels of LH and testosterone, though these changes were considered to be incidental and not involved in the other changes described above. None of the above changes were induced by a pharmacologically active dose (1 mg/kg) of GR40370X. It is concluded that the mechanism of testicular toxicity induced by 750 mg/kg GR40370X results from primary effects on the vasculature of the testis/neighbouring region, which in turn lead to impaired fluid resorption from the efferent ducts and rete and thence to accumulation of seminiferous tubule fluid in the rete and testis.     

Testicular toxicity induced in dogs by nefiracetam, a neutrotransmission enhancer

To investigate mechanisms of the testicular toxicity of nefiracetam and to find sensitive parameters to predict the toxicity, male beagle dogs were orally administered 180 or 300 mg/kg per day of the drug once and for 1 and 4 weeks. Time-course changes in serum and/or testicular hormone levels and semen parameters, and testicular morphology were examined. The testicular testosterone level was decreased 4 h after single administration of nefiracetam at 300 mg/kg per day, but the progesterone level showed no change at that time. The serum testosterone level was decreased after single, 1-week or 2-week treatment. In contrast, the serum estradiol level was increased from 1- to 4-week treatment. No changes in serum LH, FSH and inhibin B levels were observed throughout the experimental period. Decreased sperm motility and increased number of malformed sperms were first observed in semen after 4-week treatment. Histopathological examination of the testis revealed moderate and severe seminiferous atrophy with multinucleated giant cell formation at 180 and 300 mg/kg per day, respectively, after 4-week treatment, but not 1-week treatment. These results show that nefiracetam decreases testicular testosterone level in dogs following single oral administration of a high dose, and induces severe morphologic changes after 4-week treatment. This reduction is shown to be a sensitive parameter to detect the toxicity, and is suggested to be induced by the impaired conversion of progesterone to testosterone in Leydig cells.     

棉酚对雄性大鼠睾酮生成的影响

给大鼠喂服醋酸棉酚每日30mg/kg,6或8wk后用放射免疫法测定血清、睾丸间质细胞液和曲精细管液中睾酮的浓度;用放射配体结合法测定睾丸中黄体生成素(LH)和卵泡刺激素(FSH)受体的含量。结果表明在上述剂量和给药时间的条件下,棉酚对垂体-睾丸轴系无影响。     

蒽贝素对雄性大鼠血浆性激素水平及附睾精子质量的影响

目的 研究蒽贝素对雄性大鼠血浆性腺激素水平、附睾精子质量、睾丸组织结构的影响,探讨蒽贝素降低雄性大鼠生育能力的作用机制。方法 给雄性性成熟大鼠sc蒽贝素铵盐溶液30 d,末次给药后2 h,测定血浆性激素水平;检查附睾精子质量;观察睾丸组织结构。结果 与对照组比较,给药30 d后,蒽贝素高、中剂量（40、20 mg/kg）组大鼠血浆睾酮、黄体生成素、卵泡刺激素水平、附睾精子活率、精子密度明显降低,组间差异有统计学意义（P＜0.05）,附睾精子畸形率和顶体完整率无明显变化,显微镜下见睾丸组织呈萎缩性病变,曲精细管扁平、塌陷,管内精母细胞减少,附睾精细管内精子稀少。结论 蒽贝素抑制丘脑-垂体-性腺轴活动,降低雄性大鼠血浆性激素水平,引起睾丸萎缩和附睾精子活率、精子密度降低,使雄性大鼠生育能力下降。     

Effects of abamectin exposure on male fertility in rats: potential role of oxidative stress-mediated poly(ADP-ribose) polymerase (PARP) activation

Despite the known adverse effects of abamectin pesticide, little is known about its action on male fertility. To explore the effects of exposure to abamectin on male fertility and its mechanism, low (1 mg/kg/day) and high dose (4 mg/kg/day) abamectin were applied to male rats by oral gavage for 1 week and for 6 weeks. Weight of testes, serum reproductive hormone levels, sperm dynamics and histopathology of testes were used to evaluate the reproductive efficiency of abamectin-exposed rats. Abamectin level was determined at high concentrations in plasma and testicular tissues of male rats exposed to this pesticide. The testes weights of animals and serum testosterone concentrations did not show any significant changes after abamectin exposure. Abamectin administration was associated with decreased sperm count and motility and increased seminiferous tubule damage. In addition, significant elevations in the 4-hydroxy-2-nonenal (4-HNE)-modified proteins and poly(ADP-ribose) (PAR) expression, as markers for oxidative stress and poly(ADP-ribose) polymerase (PARP) activation, were observed in testes of rats exposed to abamectin. These results showed that abamectin exposure induces testicular damage and affects sperm dynamics. Oxidative stress-mediated PARP activation might be one of the possible mechanism(s) underlying testicular damage induced by abamectin.     

Insights into testicular damage induced by ethinylestradiol in rats

The present study was conducted to clarify the mechanisms of testicular toxicity induced by ethinylestradiol using a rat model maintaining testicular testosterone levels. Twelve-week-old male SD rats were implanted subcutaneously with testosterone (800 mg)-filled tubes on the back 2 days before ethinylestradiol treatment, and subsequently administered orally 10 mg/kg/day ethinylestradiol for 4 consecutive weeks. At termination, measurements of hormone levels in serum and the testis, sperm head counts in the testis, weights of genital organs and histopathological examination were performed. Results show that the supply of testosterone alone induced markedly increased serum testosterone levels, slightly decreased testicular testosterone levels, and atrophic Leydig cells. Treatment of rats with ethinylestradiol alone significantly decreased testosterone levels in serum and the testis, sperm head counts, and weights in the testis, epididymis and prostate. Histological features included atrophy of Leydig cells, decreased number of elongated spermatids, degeneration of germ cells, and tubular atrophy. Co-administration of testosterone almost completely prevented the aforementioned changes brought about by ethinylestradiol, except for Leydig cell atrophy. From these results, we attribute testicular toxicity during ethinylestradiol exposure to the suppression of testicular testosterone levels.     

Time course of the tri-o-cresyl phosphate-induced testicular lesion in F-344 rats: enzymatic, hormonal, and sperm parameter studies

Tri-o-cresyl phosphate (TOCP), a known neurotoxic compound, causes testicular toxicity in both leghorn roosters and Fischer 344 rats. The present study was initiated to follow the onset of the testicular lesion through possible changes in sperm numbers and production, serum hormones, and various enzyme activities. Rats were administered TOCP daily (150 mg/kg) for periods of 3, 7, 10, 14, or 21 days. Vehicle-treated animals served as controls. Sperm motility and sperm number per milligram cauda epididymis were both lower in treated animals by Day 10. Testicular weight to body weight ratio was significantly decreased only in the longest treatment duration animals (21 days). Testicular neurotoxic esterase and nonspecific esterase activities were also inhibited, while beta-glucuronidase activity was not affected. Luteinizing and follicle-stimulating hormone levels were normal, as were both serum and interstitial fluid testosterone concentrations. Sertoli cell fluid secretion, as measured by testis weight increase after efferent duct ligation, showed no significant changes. Other organs (spleen, liver, kidney, pancreas, small intestine, adrenal and pituitary glands) had no overt signs of pathology as observed by light microscopy in animals treated for 21 days. A separate group of animals was treated for 21 days and subsequently examined after 98 days of observation (two cycles of the rat seminiferous epithelium). No recovery of spermatogenesis was seen, indicating that the toxicity was irreversible at the dose used. The effects noted in these studies further define the testicular lesion produced by TOCP and show that 150 mg/kg/day for 21 days produced irreversible testicular toxicity.     

杨梅黄酮对铅染毒雄性小鼠生精功能及激素水平的影响#br#

目的 研究杨梅黄酮（myricetin）对铅染毒所致雄性小鼠生精障碍的影响,并探讨其作用机制。方法 选 取昆明种小鼠60只,随机分成对照组、染铅组、甲睾酮组（10 mg/kg,即阳性对照组）及杨梅黄酮低、中、高剂量组,每组 10只,除对照组外,其他5组采用腹腔注射醋酸铅（20 mg/kg,7 d）建立雄性小鼠生精障碍模型,造模第2天始,杨梅黄 酮低、中、高剂量组分别灌胃杨梅黄酮 100、200、400 mg/kg,连续 42 d。观察雄性小鼠的睾丸指数、精子密度、精子畸 形率变化,检测血清中睾酮（T）、卵泡刺激素（FSH）、黄体生成素（LH）及睾丸组织中的山梨醇脱氢酶（SDH）、丙二醛 （MDA）水平的变化,HE染色观察睾丸组织的病理改变。结果 与染铅组比较,杨梅黄酮各剂量组的精子密度增高、 睾丸指数增大、精子畸形率降低,杨梅黄酮各剂量组血清LH、FSH含量降低,T升高,睾丸组织中MDA含量降低、SDH 活性增高（P＜0.05）。睾丸组织镜下可见染铅组生精上皮变薄,生精细胞层次和数量减少,生精小管腔见少量精子形 成,而杨梅黄酮中、高剂量可改善醋酸铅所致的睾丸组织改变。结论 杨梅黄酮可通过抗氧化作用、减轻醋酸铅所 致睾丸组织氧化应激损伤,促进睾酮的分泌,提高睾丸及精子活性,从而改善睾丸的生精功能。     

Investigation of testicular toxicity of nefiracetam,a neurotransmission enhancer,in rats

Testicular toxicity of nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide), a neurotransmission enhancer, was investigated in male Slc:SD rats. Nefiracetam was orally administered daily at 1500 mg/kg for 4 weeks, and the animals were killed sequentially during the course of administration to determine testicular histopathological changes and sperm head counts (SHC), and hormonal changes. Retention of step 19 spermatids, sporadic degeneration of pachytene spermatocytes and step 7 spermatids in the stage VII seminiferous tubules, and a decrease in SHC were seen as earliest changes after 1 week of administration. These changes gradually advanced up to atrophy of seminiferous tubules with multinucleated-giant-cell formation after 4-week administration. Serum and testicular testosterone levels were decreased, but recovered to the control levels within a day following a single administration, and the decreases were repeated after 1-week administration. These results suggest that nefiracetam-induced earliest changes could be caused by the decreased level of testicular testosterone.     

Inhibitory effect of tributyltin on expression of steroidogenic enzymes in mouse testis

Tributyltin (TBT) is known to disrupt the development of reproductive organs, thereby reducing fertility. The aim of this study was to evaluate the acute toxicity of TBT on the testicular development and steroid hormone production. Immature (3-week-old) male mice were given a single administration of 25, 50, or 100 mg/kg of TBT by oral gavage. Lumen formation in seminiferous tubule was remarkably delayed, and the number of apoptotic germ cells found inside the tubules was increased in the TBT-exposed animals, whereas no apoptotic signal was observed in interstitial Leydig cells. Reduced serum testosterone concentration and down-regulated expressions of the mRNAs for cholesterol side-chain cleavage enzyme (P450scc), 17alpha -hydroxylase/C(17-20) lyase (P450(17alpha)), 3beta -hydroxysteroid-dehydrogenase (3beta -HSD), and 17beta -hydroxysteroid-dehydrogenase (17beta -HSD) were also observed after TBT exposure. Altogether, these findings demonstrate that exposure to TBT is associated with induced apoptosis of testicular germ cells and inhibition of steroidogenesis by reduction in the expression of steroidogenic enzymes in interstitial Leydig cells. These adverse effects of TBT would cause serious defects in testicular development and function.     

Testicular toxicity of dietary 2,2-bis(4-hydroxyphenyl)propane (bisphenol A) in F344 rats

Male F344/DuCrj (Fischer) rats were given bisphenol A (BPA) in the diet at levels of 0 (control), 0.25, 0.50 and 1.00%, equivalent to 0, 235, 466 and 950 mg/kg per day, respectively, for 44 days. Body weight gains were depressed dose-dependently in BPA-treated rats, and those of 0.50 and 1.00% groups were significant. Testis and epididymis weights were not significantly decreased. Both absolute and relative weights of dorsolateral prostate and preputial glands were reduced in a dose-related fashion. Absolute weights of seminal vesicles and hypophysis were also decreased. Histopathologically, seminiferous tubule degeneration and loss of elongated spermatids were observed, the severity being related to BPA dose. The disorganization, distortion and degeneration of late spermatids, and the atrophy of seminiferous tubules were found even in the 0.25% BPA group. Serum testosterone concentrations were not decreased in BPA-treated groups. These results indicate that BPA even at a level of 0.25% (235 mg/kg per day) is clearly toxic to male reproductive organs.     

Effects of neonatal exposure to 4-tert-octylphenol, diethylstilbestrol, and flutamide on steroidogenesis in infantile rat testis.

Exposure of neonatal testis, populated by fetal-type Leydig cells, to endocrine-active compounds may have far-reaching consequences. Our aim was to resolve the sensitivity of testosterone synthesis of infant rat (Sprague-Dawley) testis to diethylstilbestrol (DES; 0.1-1.0 mg/kg), 4-tert-octylphenol (OP; 10-100 mg/kg), and Flutamide (FLU; 2.0-25 mg/kg) given by daily sc injections from birth to postnatal day 4. Testes and serum were collected on day 14 when body and testis weight, testicular histology, circulating testosterone, LH and FSH levels, and steroidogenic acute regulatory protein (StAR) and 3beta-hydroxy-steroid-dehydrogenase (3beta-HSD) protein levels were determined. DES at each dose and FLU at 25 mg/kg dose reduced testis weight and the diameter of seminiferous cords. FLU caused some Leydig cell hyperplasia. Plasma testosterone was reduced in all DES animals, LH elevated in DES 0.5 mg/kg and FLU 25 mg/kg animals, and FSH reduced in the DES 1.0 mg/kg group. Basal testicular ex vivo progesterone and human chorionic gonadotropin (hCG)-stimulated testosterone production were decreased in DES animals. Despite a decrease in hCG-induced cyclic adenosine-3',5'-monophosphate (cAMP) production, intratesticular testosterone was increased in the FLU 10 and 25 mg/kg groups. OP 100 mg/kg elevated hCG-induced progesterone production only. No changes were seen in 3beta-HSD protein levels in any treatment group. StAR levels were reduced in DES animals. The results indicate the sensitivity of postnatal fetal-type Leydig cells to endocrine-active compounds. Suppression of StAR expression level was an early sign of the DES-induced steroidogenic lesion. FLU-induced changes suggest the importance of androgen receptor-mediated regulation of testosterone synthesis in the postnatal rat testis. Octylphenol appeared less effective in bringing about acute steroidogenic changes.     

Tangeretin ameliorates erectile and testicular dysfunction in a rat model of hypertension

Tangeretin is a polymethoxyflavone concentrated in citrus peels and has several biological activities. This study examined whether tangeretin improved reproductive dysfunction in N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats received L-NAME to induce hypertension and reproductive dysfunction for 5 w and were treated with tangeretin (15 or 30 mg/kg) or sildenafil citrate (10 mg/kg) for the final two weeks. Mean arterial pressure (MAP), intracavernosal pressure (ICP) response to cavernous nerve stimulation, endothelial nitric oxide synthase (eNOS), Angiotensin II receptor type 1 (AT₁R) and gp91^phox protein expressions and malondialdehyde (MDA) level in penile tissues were measured. Sperm concentrations and motility, seminiferous tubule morphology, serum testosterone, testicular eNOS and steroidogenic acute regulatory protein (StAR) expression were evaluated. Aortic superoxide generation, plasma and testicular MDA and plasma nitrate/nitrite levels were determined. Tangeretin reduced blood pressure and increased the maximum ICP/MAP associated with suppression of AT₁R/gp91phox and upregulation of eNOS expression in hypertensive rats (P < 0.05). Furthermore, improvement of sperm quality relevant to increased testicular eNOS and StAR expression was found in tangeretin treated rats (P < 0.05). Changes in seminiferous tubule morphology in hypertensive rats were recovered by tangeretin (P < 0.05). It increased testosterone levels and reduced oxidative stress biomarkers and raised plasma nitrate/nitrite levels in L-NAME rats (P < 0.05). In conclusion, tangeretin improved maximum ICP/MAP and testicular dysfunction and morphology in rats treated with L-NAME. The molecular mechanisms are mediated by modulations of penile eNOS and AT₁R/gp91^phox expressions and testicular eNOS and StAR expression.     

Reproductive toxicity of 2,4-toluenediamine in the rat. 3. Effects on androgen-binding protein levels, selected seminiferous tubule characteristics, and spermatogenesis

In previous studies we demonstrated reduced fertility, arrested spermatogenesis, and diminished circulating testosterone levels in rats fed 0.03% 2,4-toluenediamine (TDA) for 10 wk. These studies were extended in three experiments by determining TDA effects on androgen-binding protein (rABP) production and on seminiferous tubule structure, and on early changes in testes morphology and spermatogenesis. In the first experiment, rats fed 0.03% TDA for 10 wk showed a 7- to 9-fold increase in rABP content in testicular cytosol or in media of cultured seminiferous tubules, a 4-fold increase in serum rABP, but a two-thirds decrease in epididymal rABP levels. Testes examination by transmission electron microscopy revealed degenerative changes in Sertoli cells with, where present, normal spermatocytes and spermatids. In the second experiment, 0.03% TDA fed for 4, 6, or 8 wk resulted in a doubling of testes/body weight ratios and a highly correlated 2.5- to 2.9-fold increase in seminiferous tubule fluid volume. An approximately 50% decrease in epididymal sperm reserves was found after 6 or 8 wk of TDA exposure. After 10 wk of exposure to 0.03% TDA, testicular weight was the same as in control-fed rats but seminiferous tubule fluid volume was still elevated. These changes in testicular characteristics indicate TDA effects on Sertoli cell function, on RABP release from the testes (and epididymides), and possibly on tubular fluid transport. In the third experiment, rats fed 0.06% TDA for 1 wk showed a 25% decrease in epididymal sperm content, reduced epididymal weight, and minor structural changes in Sertoli cells. After 3 wk of 0.06% TDA feeding, sperm counts were further reduced, and were accompanied by a dramatic increase in testes weight, intense fluid accumulation, and ultrastructural changes in Sertoli cells. No significant changes in serum testosterone levels were noted in the TDA-treated rats. The results of this third experiment demonstrate TDA toxicity on testicular spermatogenesis within 3 wk of TDA feeding. The within 3 wk of TDA feeding. The findings in this study suggest that the early inhibition of spermatogenesis by TDA is mediated through Sertoli cell damage.     

Quantitative aspects of spermatogenesis in rats and dogs after repeated hexachlorophene treatment

Hexachlorophene was administered orally, at subneurotoxic doses, to rats (5 mg/kg/day) and dogs (3 mg/kg/day) for 9 weeks: some of the rats and dogs were observed for a further 13 weeks. The serum concentrations of pituitary gonadotrophin and testosterone were unaffected in either species. No changes were induced in the testicular dimensions or semen characteristics of dogs and no macroscopic post mortem abnormalities, organ weight differences or lesions detectable by conventional light microscopy were found in their testes, pituitaries or secondary sex organs. A transient reduction in the number of germ cells counted in cross-sections of seminiferous tubules was seen in rats after 4 weeks treatment. After 9 weeks treatment, reduced spermatogonial counts were recorded in canine seminiferous tubules; in other respects spermatogenesis was proceeding normally. No delayed effects were apparent in either species. It is concluded that repeated administration of hexachlorophene at subneurotoxic levels did not induce significant impairment of spermatogenesis in rats or dogs.     

Co-administration of toluene and xylene antagonized the testicular toxicity but not the hematopoietic toxicity caused by ethylene glycol monoethyl ether in Sprague-Dawley rats.

Occupational painters are exposed to ethylene glycol monoethyl ether (EGEE), a widely used emulsifying solvent known to cause testicular degeneration and bone marrow depression, together with toluene (TOL) and xylene (XYL) as a mixture. In the previous study (Chung et al., Tox. Lett. 104:143, 1999), testicular atrophy caused by EGEE (200 mg/kg) was shown to be antagonized by co-administration of TOL (250 mg/kg) and XYL (500 mg/kg). This study was conducted to provide histological support for the previously observed antagonistic protective effect of TOL + XYL on EGEE inducible testicular toxicity and to determine whether a similar antagonistic effect can be demonstrated against the EGEE derived hematopoietic toxicity. Compared to the extent of seminiferous tubule degeneration caused by EGEE (150 mg/kg, six times per week for 4 weeks), testes of rats given co-administration of TOL (250 mg/kg) + XYL (500 mg/kg) showed dramatically reduced tubular degeneration. Hyperplasia of Leydig cells in the interstitium was observed in both EGEE and EGEE + TOL + XYL-treated rats. Although a minimal dose of EGEE causing testicular atrophy was used, WBC and platelet counts were decreased significantly. In the TOL + XYL-treated control group, the WBC and platelet counts were not decreased. However, the bone marrow depression caused by EGEE was not reversed by the combined administration of TOL + XYL. In all experimental groups (EGEE alone, TOL + XYL, EGEE + TOL + XYL), plasma levels of creatinine and alkaline phosphatase were significantly decreased. In addition to the marked testicular atrophy, EGEE also decreased the weights of adrenal glands and epididymis. In conclusion, while the testicular degeneration caused by EGEE was antagonized by TOL + XYL, the EGEE derived hematopoietic suppression was not reversed.     

Quantitative assessment of spermatogenesis in rats given 1-amino-3 chloro-2 propanol hydrochloride (CL 88, 236)

A quantitative histomorphometric assessment of testicular spermatogenesis was undertaken on testes from rats which had received 1-amino-3 chloro-2 propanol hydrochloride (CL 88, 236) at oral doses of 0, 50, 250 or 500 mg/ kg/day for 12 weeks. Rats which developed epididymal sperm granulomata or severe atrophy of the germinal epithelium were excluded from quantitative examination. Pathological changes in the epididymis and seminiferous epithelium were not strongly correlated. CL 88, 236 administered at 50 mg/ kg/day was without effect on the histomorphometry of the seminiferous epithelium, although epididymal lesions occurred at this dose. At higher doses a quantitative reduction in testicular spermatids was evident. It appears important to differentiate between the selective antifertility action of CL 88, 236 on the biochemistry of epididymal spermatozoa and the disruption of epididymal physiology, and testicular spermatogenesis found at unusually high doses.     

Effects of abamectin exposure on male fertility in rats: Potential role of oxidative stress-mediated poly(ADP-ribose) polymerase (PARP) activation

Despite the known adverse effects of abamectin pesticide, little is known about its action on male fertility. To explore the effects of exposure to abamectin on male fertility and its mechanism, low (1 mg/kg/day) and high dose (4 mg/kg/day) abamectin were applied to male rats by oral gavage for 1 week and for 6 weeks. Weight of testes, serum reproductive hormone levels, sperm dynamics and histopathology of testes were used to evaluate the reproductive efficiency of abamectin-exposed rats. Abamectin level was determined at high concentrations in plasma and testicular tissues of male rats exposed to this pesticide. The testes weights of animals and serum testosterone concentrations did not show any significant changes after abamectin exposure. Abamectin administration was associated with decreased sperm count and motility and increased seminiferous tubule damage. In addition, significant elevations in the 4-hydroxy-2-nonenal (4-HNE)-modified proteins and poly(ADP-ribose) (PAR) expression, as markers for oxidative stress and poly(ADP-ribose) polymerase (PARP) activation, were observed in testes of rats exposed to abamectin. These results showed that abamectin exposure induces testicular damage and affects sperm dynamics. Oxidative stress-mediated PARP activation might be one of the possible mechanism(s) underlying testicular damage induced by abamectin.     

Testicular effects of the Leydig cell toxicant ethane dimethanesulphonate given to neonatal rats.

Neonatal rats were injected with either 50 mg/kg ethane dimethanesulphonate (EDS) or vehicle on days 1 to 5 inclusive or on day 1 alone. Studies were made on days 6, 28, and 63 of testicular structure; related endocrinologic parameters were measured in the day 1 to 5 treated animals only. Leydig cells and their activities were identified by cell counts using sections stained for 3 beta-hydroxysteroid dehydrogenase, hCG binding to LH receptors in testicular homogenates, and assays of intratesticular testosterone, plus pituitary and/or serum concentrations of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH). Given on days 1 to 5, EDS reduced Leydig cell populations estimated by morphometry and 125I-HCG binding, and testicular and body weights between days 6 and 63, and permanently retarded the development of the seminiferous epithelium. Decreases of serum and intratesticular testosterone occurred with homeostatic rises in FSH and LH. Injection on day 1 reduced Leydig cell numbers only on day 6 although body weight remained retarded. The data illustrate the susceptibility of the developing rat testis to the cytotoxicant EDS; whether this is related to withdrawal of androgen production or nonspecific cytotoxicity remains to be evaluated.