农达染毒对30d龄雄性大鼠睾丸及附睾某些指标的影响

目的研究农达染毒对30 d龄雄性大鼠睾丸和附睾毒性、精子毒性及血清睾酮水平的影响,为农达的职业健康危险度评定提供科学依据。方法 30 d龄雄性SD大鼠40只,按体重随机分为4组,染毒低、中、高剂量组分别给250、500和1 000 mg/kg·bw的农达,连续灌胃30 d,对照组给予等量去离子水。观察各组大鼠一般情况,睾丸和附睾的脏器系数、病理学改变;精子总数、精子畸形率;用放免法测定各组大鼠血清睾酮含量。结果 1 000 mg/kg·bw染毒组大鼠睾丸和附睾系数明显下降(P0.01);染毒组大鼠生精小管上皮变薄,细胞层排列紊乱,生精细胞数目明显减少,附睾管腔中线状精子数减少;各染毒组大鼠精子总数均明显降低(P0.05),精子畸形率均明显升高(P0.05),精子畸形率与染毒剂量之间存在剂量-反应关系(P0.01);各染毒组大鼠血清睾酮含量均明显下降(P0.01)。结论 30 d龄雄性大鼠农达染毒可诱导其生殖毒性,表现为精子数量下降、畸形率增加和血清睾酮含量降低。     

虾青素对甲醛致雄性小鼠精子损伤的保护作用研究

目的探讨虾青素对甲醛诱导的雄性小鼠精子损伤的保护作用。方法 48只昆明种系雄性小鼠,按随机数字表法分为4组,即正常对照组、甲醛染毒模型组、虾青素高剂量组(80mg·kg-1·d-1)、低剂量组(20mg·kg-1·d-1)。连续染毒7d后,虾青素持续灌胃21d,处死小鼠,进行附睾精子计数、精子活动度及精子畸形率分析,睾丸组织行超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量测定。结果甲醛染毒组小鼠精子数量、活动度,睾丸组织SOD明显低于正常对照组(P<0.05),精子畸形率、MDA含量高于正常对照组(P<0.05)。虾青素高、低剂量组精子数量、活动度,睾丸组织SOD高于甲醛染毒组(P<0.05),精子畸形率、MDA含量低于甲醛染毒组(P<0.05)。结论虾青素对甲醛诱导的雄性小鼠精子损伤一定的保护作用,可改善甲醛染毒小鼠的精子数量、活动度,降低精子畸形率,其作用机制可能与提高睾丸组织SOD水平、降低MDA含量有关。     

双酚A对小鼠睾丸组织氧化损伤及生殖细胞凋亡的影响

目的研究双酚A(bisphenolA,BPA)对雄性小鼠睾丸组织氧化损伤及其对生殖细胞凋亡的影响。方法将52只健康成年雄性昆明种小鼠随机分为溶剂对照组(玉米油)和低(75 mg/kg·bw)、中(150 mg/kg·bw)、高(300 mg/kg·bw)剂量组,每组13只,连续经口染毒8周。处死小鼠后,解剖取材,称量睾丸的重量并计算脏器系数;取附睾,制成精子混悬液于镜下观察精子活动率、统计精子畸形率;采用酶标仪检测睾丸组织匀浆中超氧化歧化酶(SOD)、乳酸脱氢酶(LDH)活力及丙二醛(MDA)含量;采用qPCR方法检测凋亡相关基因CytC、Caspase-3及Bcl-2 mRNA表达量。结果各染毒剂量组较对照组睾丸脏器系数升高,精子活力随剂量升高明显降低(P0.05);精子畸形数及精子畸形率均随剂量升高明显升高(P0.05);各染毒剂量组睾丸组织SOD、LDH酶活力及MDA含量均升高,差异有统计学意义(P0.05);各染毒剂量组睾丸组织中CytC及Caspase-3 mRNA表达量较对照组均升高,Bcl-2 mRNA表达量较对照组降低,差异有统计学意义(P0.05)。结论 BPA引起雄性小鼠睾丸组织的氧化损伤及生殖细胞凋亡。     

邻苯二甲酸二辛酯对大鼠睾丸,附睾及精子损伤的时间效应

本文报道了大鼠连续灌胃染毒200、1000、5000mg/kg/天邻苯二甲酸二辛酯4周,分别在染毒第1、2、3、4周和染毒4周恢复2周观察大鼠睾丸、附睾及精子的改变。结果发现,染毒2周开始出现睾丸、附睾严重萎缩,并伴有附睾尾精子数量显著减少;精子死亡率及畸变率明显增加。存在剂量反应及时间效应关系。精子数量、畸形、活力与睾丸、附睾萎缩存在明显相关。恢复期,睾丸、附睾及精子损伤回复到对照组水平,提示短期暴露邻苯二甲酸二辛酯对大鼠睾丸,附睾及精子损伤为可逆性毒性效应。     

二乙氧基乙醇对大鼠睾丸生精细胞中Bax、细胞色素C和Caspase-3表达的影响

目的研究二乙氧基乙醇(2-Ethoxyethanol,2-EE)对大鼠睾丸生精细胞中Bax,细胞色素C(Cytochrome C,CytC)以及Caspase-3表达的影响,探讨其在生精细胞凋亡调控中的作用。方法选择Wistar大鼠,分别给予剂量400、800和1200mg/kg的2-EE,连续灌胃7d,对照组以等量生理盐水灌胃,分别于末次染毒后第1和29天处死动物。采用免疫组化法(SP法),观察不同剂量染毒后及自然恢复4周后生精细胞中Bax,CytC以及Caspase-3的表达情况。结果400、800和1200mg/kg染毒7d后,大鼠睾丸生精细胞中Bax,CytC以及Caspase-3的表达水平不同程度的上升,尤其以800mg/kg组最为明显。自然恢复4周后,生精细胞中Bax,CytC以及Caspase-3的表达基本接近对照组水平。结论在本试验条件下,2-EE急性染毒可能通过影响大鼠睾丸生精细胞中Bax,CytC和Caspase-3的释放,调控生精细胞凋亡,与2-EE所致睾丸毒性的可恢复性高度相关。     

二乙氧基乙醇雄性大鼠生殖系统毒性研究

目的 观察研究二乙氧基乙醇(2-Ethoxyethanol,2-EE)染毒雄性大鼠睾丸和附睾毒性、精子毒性、以及性行为与妊娠率的改变,探讨各生殖毒性指标之间的关联性,为确定2-EE雄性生殖毒性健康监护指标和诊断指标,开展2-EE职业健康危险度评价提供科学依据.方法 选择清洁级雄性Wistar大鼠,分别给予剂量200、4...     

低剂量毒死蜱重复染毒诱发雄性大鼠生殖毒性及其机制

目的探讨毒死蜱(CPF)低剂量重复染毒对雄性大鼠生殖功能的影响及其可能作用机制。方法健康雄性Wistar大鼠ig给予CPF 1,5和10 mg.kg-1,每日1次。连续染毒12周后取大鼠附睾和睾丸称重计算脏器系数,进行组织病理学、精子数量以及活力及畸形率等检查,测定睾丸碱性磷酸酶(AKP)、酸性磷酸酶(ACP)、γ-谷氨酰转肽酶(γ-GT)和乳酸脱氢酶(LDH)的活性;TUNEL法检测细胞凋亡,免疫组化及Western印迹法检测胱天蛋白酶和Fas,FasL蛋白的表达。结果与正常对照组相比,CPF染毒大鼠睾丸脏器系数显著升高,精子数及精子活力降低,精子畸形率显著升高(P<0.05),睾丸AKP和γ-GT活性抑制明显。组织病理检查显示,睾丸曲细精管疏松和生精细胞减少。CPF染毒组生精细胞凋亡增加(P<0.05)。Fas/FasL蛋白表达量升高。结论 CPF低剂量重复染毒能够诱导雄性大鼠生殖毒性,其作用机制可能与激活Fas/FasL受体途径而引起睾丸生精细胞凋亡有关。     

3种方式染毒丙烯酰胺对雄性小鼠早期精细胞微核的影响

目的研究腹腔注射、灌胃、皮肤染毒丙烯酰胺(AA)对小鼠早期精细胞微核发生率的影响,以反映相应的遗传毒性。方法将24只清洁级健康雄性昆明小鼠随机分为4组,分别为空白对照组、腹腔注射染毒组、灌胃染毒组和皮肤染毒组,每组6只。染毒剂量为25 mg/kg,每天1次,连续染毒5 d。首次染毒后第19天称体重和睾丸重量,计算睾丸系数。采用早期精细胞微核实验测定各组小鼠早期精细胞微核的发生率。结果染毒后腹腔注射染毒组、灌胃染毒组和皮肤染毒组小鼠体重均低于空白对照组,差异有统计学意义(P<0.05或P<0.01);与空白对照组比较,腹腔注射染毒组、灌胃染毒组和皮肤染毒组小鼠的睾丸重量均较低,差异有统计学意义(P<0.05);与空白对照组比较,腹腔注射染毒组和皮肤染毒组小鼠早期精细胞微核发生率较高,但差异无统计学意义(P>0.05),灌胃染毒组小鼠早期精细胞微核发生率高,差异有统计学意义(P<0.05)。结论 AA可致雄性小鼠早期精细胞微核发生率增高,且以灌胃染毒方式产生的毒性作用最为敏感。     

乙二醇对雄性大鼠生殖系统的影响

Wistar雄性大鼠,乙二醇连续灌胃染毒13周,剂量分别为333、666、1332和2664mg/kg。结果表明,与对照组比各剂量组的活动精子百分率明显降低,精子畸形率明显增加(P<0.01);666mg/kg组大鼠的肾脏脏器系数明显高于对照组(P<0.05);1332mg/kg组雄性大鼠的交配率、生育指数明显下降(P<0.05),血清睾丸酮和LH水平明显降低(P<0.01),对睾丸和前列腺有明显影响,生长明显受抑;2664mg/kg组除以上指标改变外,精子数明显减少,胎吸收率非常明显升高,各组的FSH水平变化不明显。对雄性大鼠生殖系统无作用剂量、阈剂量和明显作用剂量分别为333m、666m和1332mg/kg。     

二恶英对子宫内膜异位症小鼠的免疫毒性

目的 探讨四氯二苯并二恶英(TCDD)对于子宫内膜异位症小鼠模型的免疫毒性.方法 采用小鼠自体子宫内膜移植法建立小鼠子宫内膜异位症模型,间隔21 d分别给予TCDD0、1、3、10μg/kg灌胃1次.建模术后3、6、9周处死,鉴定异位病灶的形成,测量异位病灶体积,摘取胸腺并称重,计算脏器系数.采用RT-PCR法检测各组小鼠异位子宫内膜组织中IL-1β mRNA水平.结果 对照组异位子宫内膜病灶逐渐萎缩消失.随着染毒时间的延长和染毒剂量的增加,染毒组异位病灶体积明显呈剂量和时间依从性增加(P<0.05).与对照组相比,染毒组胸腺脏器系数呈现时间和剂量依赖性降低(P<0.05).异位灶体积和胸腺脏器系数之间具有明显的负相关性(P<0.05).与对照组相比,染毒组小鼠异位子宫内膜中IL-1β mRNA表达较对照组明显呈剂量和时间依从性上调(P<0.01).结论 TCDD可促进模型小鼠异位子宫内膜病灶的发展,其机制可能与系统性和局部性免疫毒性有关.     

Potential testicular toxicity of sodium nitrate in adult rats

Nitrate is a common contaminant in groundwater aquifers. Current study aimed at evaluating the potential testicular toxicity of sodium nitrate in rats. Sodium nitrate was given orally to rats at doses of 50, 100 or 200 mg/kg/day for 60 consecutive days. Sperm count and motility, daily sperm production and testis weight were significantly decreased specially at high doses. Testicular activity of lactate dehydrogenase-X, glucose-6-phosphate dehydrogenase, and acid phosphatase were inhibited in a dose-related manner. Lipid peroxides and hydrogen peroxide production were significantly increased in all treated animals. This was accompanied by inhibition of testicular activities of superoxide dismutase and glutathione peroxidase. Fifty mg/kg of sodium nitrate did not significantly alter catalase or glutathione reductase activity. Glutathione was significantly decreased by sodium nitrate in a dose-related manner. The decrease in sperm count and motility and daily sperm production was confirmed by histopathological studies which indicated chromatolysis, pyknosis and necrosis in spermatocytes. In conclusion, subchronic exposure of rats to sodium nitrate results in testicular toxicity as evidenced by decreased sperm count and motility, daily sperm production and testis weight, inhibited activity of enzyme markers of spermatogenesis and induction of histopathological changes. These effects are attributed, at least partly, to testicular oxidative stress.     

A purine nucleoside analogue-acyclovir [9-(2-hydroxyethoxymethyl)-9h-guanine] reversibly impairs testicular functions in mouse

The present study was designed to investigate testicular effects of Acyclovir [9-(2-hydroxyethoxymethyl)-9H-guanine] in mouse. Swiss albino male mice (N=6/group/dose/sample time) were treated (i. p.) every day with 4, 16, 32, and 48 mg/kg body weight of Acyclovir for 15 d. The testis was examined for histopathological changes and the seminiferous tubular diameter (STD) and epithelial height (SE) were measured. The sperm count, sperm motility and sperm morphology assay in caudae epididymes, and intra-testicular levels lactate dehydrogenase (LDH) and testosterone were estimated on 7 d, 14 d, 21 d, 28 d, 35 d, and 70 d, following the last exposure. Acyclovir did not affect the body weight, but decreased the testis weight on 21 d and 28 d at two higher dose-levels, and on 35 d at all dose-levels. The STD was decreased on 21 d at 16-48 mg/kg dose-levels (p<0.01), on 28 d and 35 d, at all dose-levels (p<0.01-0.001). The SE was decreased on 14 d at two higher dose-levels (p<0.01), thereafter up to 35 d at all dose-levels (p<0.001). Acyclovir decreased the sperm count from 7-35 d (p<0.001) with a recovery observed on 70 d, except at 48 mg/kg dose-level (p<0.05), and inhibited the sperm motility (p<0.001) from 7-35 d with a maximum effect on 28-35 d. On the other hand, sperm abnormalities increased on 21 d, 28 d and 35 d at 16-48 mg/kg, at 32-48 mg/kg, and at 32 mg/kg dose-levels, respectively (P<0.05). LDH activity was increased (p<0.05-0.001) from 7 d (except at 4 mg/kg) to 35 d. Only 48 mg/kg dose group showed increase in LDH concentration on 70 d. In conclusion, Acyclovir is cytotoxic to germ cells inducing the cellular destruction, and reducing the sperm count and motility, and increasing sperm abnormalities. Further, Acyclovir also caused cellular destruction thus releasing LDH from the cells, and affecting the Leydig cell function. All adverse effects of Acycovir are reversible by 70 d, except the sperm count and LDH level, which appear to be affected over an extended period of time at a higher dose-level.     

Impairment of mice spermatogenesis by sodium arsenite

In order to assess the effect of arsenic on the male reproductive impairment in mice, 7-week-old animals were exposed to 7.5 mg sodium arsenite (NaAsO(2))/kg body weight, during 35 days (one spermatogenic cycle). One group of animals was sacrificed after exposure, while another group received distilled water for an additional period of 35 days, in order to study the spermatoxic effect and the recovery of spermatogenesis. In mice sacrificed after NaAsO(2) exposure, a decrease in testis/body weight ratio and reduction of tubular diameter were observed. Both groups of NaAsO(2)-exposed animals showed remarkable histopathological changes, such as sloughing of immature germ cells. Animals sacrificed after NaAsO(2) exposure showed decreased sperm motility, increased abnormal sperm morphology and decreased sperm viability. The effects of NaAsO(2) on sperm motility recovered to normal values after one spermatogenic cycle, while increased sperm abnormality was maintained. However, at this period, a decrease in acrosome integrity was detected. Concerning oxidative stress parameters, animals sacrificed after NaAsO(2) exposure showed a decreased selenium-dependent glutathione peroxidase activity, which was not detected after the recovery. Conversely, at this period, total glutathione peroxidase activity increased in exposed animals. These results demonstrate the toxic effects of NaAsO(2) on mice spermatogenesis and show the lack of recovery after one spermatogenic cycle.     

Reproductive toxicity of sodium valproate in male rats

Objectives:

To assess the effects of sodium valproate on rat sperm morphology, sperm count, motility, and histopathological changes in testis.

Materials and Methods:

Male Wistar rats (12 week old) were treated with sodium valpraote and sacrificed at the end of 2^nd, 4^th, 5^th, 7^th, 10^th and 15^th week after the last exposure to sodium valproate. Epididymal sperm count, sperm motility, sperm morphology, and histopathology of testes were analyzed.

Results:

Sperm count and sperm motility were decreased significantly by sodium valproate. The percentage of abnormal sperms increased in a dose-dependent manner. A histopathological study revealed that sodium valproate had caused sloughing of epithelial cells in testes.

Conclusion:

Sodium valproate causes reversible change in sperm motility, sperm count, morphology, and cytoarchitecture of testes.     

Reproductive toxicology of methyldopa in male F344/N rats

Methyldopa, a widely used antihypertensive drug, was administered to male Fischer 344/N rats by gavage 5 days/week for 65 days at dosages of 0, 50, 100, 200, or 400 mg/kg. Decreased body weight was seen in treated animals. After mating to untreated female Fischer 344/N rats on days 57-61, the male rats were necropsied (days 65-67) and reproductive toxicity was measured by sperm count, sperm motility, organ weights, hormone levels and histologic evaluation of the testis. Decreased fertility was seen in males dosed with 200 or 400 mg/kg methyldopa. Decreases were also seen in sperm count, sperm motility, apparent number of late spermatids, and plasma testosterone levels in males in the 200 and 400 mg/kg groups. This alternation of reproductive function in male rats was found to be reversible after a 13-week recovery period without dosing. The marked decrease in circulating testosterone levels following methyldopa treatment at 200 or 400 mg/kg may have contributed to the reproductive toxicity of this drug.     

Evaluation of ameliorative effect of curcumin on imidacloprid‐induced male reproductive toxicity in wistar rats

This study was undertaken to investigate the toxic effects of imidacloprid (IM) on male reproductive system and ameliorative effect of curcumin (CMN) in male Wistar rats. For this purpose, IM (45 and 90 mg/kg, body weight) and CMN (100 mg/kg, body weight) were administered orally to the rats either alone or in combinations for a period of 28 days. At the end of experiment, male reproductive toxicity parameters (total sperm count and sperm abnormalities), testosterone level, steroidal enzymatic activity [3β‐hydroxysteroid dehydrogenase (3β‐HSD) and 17β‐HSD], and oxidative stress indicators were estimated in testis and plasma. IM treatments resulted in significant decrease (p < 0.05) in total epididymal sperm count, sperm motility, live sperm count, and increase (p < 0.05) in sperm abnormalities. Activities of gamma‐glutamyl transpeptidase, lactate dehydrogenase‐x, and sorbitol dehydrogenase were significantly increased (p < 0.05), while, 3β‐HSD and 17β‐HSD enzymatic activity along with testosterone concentration in testis and plasma were decreased significantly (p < 0.05) in IM‐treated rats. IM exposure resulted in significant increase (p < 0.05) in LPO and decrease (p < 0.05) in GSH level along with decreased activities of CAT, SOD, GPx, and GST. IM‐treated rats showed histopathological alterations in testis and epididymis. However, the reproductive toxicity parameters, oxidative stress indicators, and histopathological changes were minimized and functional restorations were noticed by co‐administration of CMN in IM‐treated rats. The results of this study suggest that IM‐induced male reproductive toxic effects could be ameliorated by CMN supplementation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1250–1263, 2016.     

Effects of indium chloride exposure on sperm morphology and DNA integrity in rats

Indium, a Group IIIA element of the periodic chart and a rare earth metal characterized by high plasticity, corrosion resistance, and a low melting point, is widely used in the electronics industry where released streams can contaminate the environment. Consequently, indium can reach humans mainly by natural ways, which could result in a health hazard. Although reproductive toxicities have been surveyed in some studies in animal models, the infertility effects of sperm function induced by indium compounds have not been greatly investigated. We designed a study to investigate the toxicities of subacute exposure to indium compounds on male sperm function and the process of spermatogenesis in a rodent model. Fourteen Sprague-Dawley rats on postnatal Day (PND) 84 were randomly divided into exposure and control groups, and weekly received intraperitoneal injections of indium chloride (1.5 mg/kg body weight) and normal saline, respectively, for 8 weeks. Cauda epididymal sperm count, motility, morphology, chromatin DNA integrity, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and testis DNA content were investigated. The indium chloride exposed group showed significant toxicity to sperm function, as well as an increased percentage of sperm morphological abnormality and chromatin DNA damage. Furthermore, positive correlations between abnormal sperm morphology, chromatin DNA damage, and superoxide anion generation were also noted. The results of this study demonstrated the toxic effect of subacute low dose indium exposure during sexual maturation on sperm function, resulting in sperm chromatin DNA damage through an increase in sperm ROS generation in a rodent model.     

Testicular toxicity effects of magnetic field exposure and prophylactic role of coenzyme Q10 and L-carnitine in mice.

The protective effect of L-carnitine or coenzyme Q10 (CoQ10) against high magnetic field (20 mT) induced testicular toxicity in mice were evaluated. Animals were injected with L-carnitine (200 mg kg(-1), i.p.) or CoQ10 (200 mg kg(-1), p.o.) 1h before exposure to fractionated doses (30 min per day, three times per week for 2 weeks) or acute dose (3h) of magnetic field. Total sperm count, motility, daily sperm production, and testicular LDH-X activity as well as histopathological examination were investigated. Exposure of mice to fractionated doses of magnetic field caused a significant decrease in sperm count, motility, daily sperm production, and LDH-X activity, which was more pronounced than that of acute dose. Moreover, a marked testicular histopathological changes were observed after exposure to fractionated doses of magnetic field. Pretreatment of mice with L-carnitine or CoQ10 1h before exposure to magnetic field caused a significant recovery of mice testes damage induced by high magnetic field (20 mT).