DEHP对雄性小鼠生殖功能的影响

为了研究邻苯二甲酸(2-乙基己基)酯(DEHP)对雄性小鼠生殖功能的影响,将40只成年健康雄性小鼠按体重为随机分成4组,即空白组和低、中、高DEHP剂量组,每组10只。空白组以生理盐水灌胃,低、中、高DEHP剂量组分别以250 mg/kg·bw、500 mg/kg·bw、1 000 mg/kg·bw DEHP灌胃,每天1次,连续4周,灌胃体积为10 m L/kg·bw。试验过程中观察动物的毛发、活动及进食情况。试验结束后处死小鼠,取小鼠睾丸与附睾称重,计算其脏器系数,并测定精子计数和精子畸形率。结果显示与空白组比较,各剂量染毒组小鼠睾丸与附睾重量及其脏器系数、精子计数均降低;精子畸形率均升高;差异均有统计学意义(P 0. 05)。随着DEHP剂量的升高,雄性小鼠睾丸与附睾重量及其脏器系数、精子计数呈下降趋势,精子畸形率呈上升趋势。表明DEHP对雄性小鼠生殖功能具有损伤作用,损伤机制有待进一步研究。     

亚急性硒中毒对小鼠精子质量的影响研究

为了研究亚急性硒中毒对小鼠精子质量的影响,试验选用雄性昆明鼠灌胃染毒。高、中、低剂量组分别按照0.135 mg/kg、0.540 mg/kg、2.160 mg/kg剂量浓度灌胃亚硒酸钠溶液,对照组灌胃纯化水,连续攻毒30 d,每隔10 d各组随机选取10只采样,检查睾丸脏器系数、精子密度、精子活率、精子畸形率。随着染硒剂量的增加和时间的延长,各染硒剂量组睾丸脏器系数呈下降趋势,小鼠精子密度和精子活率随染硒剂量的增加逐渐减小,各染硒组小鼠的精子畸形率均有增加,呈现明显的时间-剂量-效应关系。结果表明：亚急性硒中毒可影响雄性小鼠生长发育,阻碍睾丸的发育甚至引起睾丸萎缩,影响精子的生成和发育,降低雄性小鼠的生殖机能。     

亚急性硒中毒对小鼠精子质量的影响研究

为了研究亚急性硒中毒对小鼠精子质量的影响,试验选用雄性昆明鼠灌胃染毒。高、中、低剂量组分别按照0.135 mg/kg、0.540 mg/kg、2.160 mg/kg剂量浓度灌胃亚硒酸钠溶液,对照组灌胃纯化水,连续攻毒30 d,每隔10 d各组随机选取10只采样,检查睾丸脏器系数、精子密度、精子活率、精子畸形率。随着染硒剂量的增加和时间的延长,各染硒剂量组睾丸脏器系数呈下降趋势,小鼠精子密度和精子活率随染硒剂量的增加逐渐减小,各染硒组小鼠的精子畸形率均有增加,呈现明显的时间-剂量-效应关系。结果表明:亚急性硒中毒可影响雄性小鼠生长发育,阻碍睾丸的发育甚至引起睾丸萎缩,影响精子的生成和发育,降低雄性小鼠的生殖机能。     

毒性剂量纳米硒对SD雄性大鼠生殖功能的影响

本试验研究毒性剂量下纳米硒(SeNPs)对SD雄性大鼠睾丸损伤、精子活力及其运动参数的影响。选取6周龄SD大鼠40只分4组,每天分别灌胃剂量为0、2.0、4.0、8.0mg/kg体质量的SeNPs 1次,连续2周,试验结束取睾丸称重,做组织切片进行光镜和电镜观察,并取附睾中的精液上机分析。结果显示,8.0mg/kg体质量剂量的SeNPs使睾丸出现严重萎缩,4.0、8.0mg/kg体质量剂量组的睾丸组织都出现了不同程度的病理损伤,8.0 mg/kg体质量剂量组的睾丸细胞染色质浓染边聚,有细胞凋亡现象。另外4.0、8.0 mg/kg体质量剂量的SeNPs会显著降低精子浓度、精子活力以及精子的运动参数,2.0mg/kg体质量剂量的SeNPs对于精子浓度和精子活力无显著影响,却提高了精子的部分运动参数。本研究提示高于4.0mg/kg体质量的SeNPs对雄性SD大鼠的生殖功能有损害。     

液态甲醛对雄性小鼠生殖毒性的研究

为研究液态甲醛对雄性昆明鼠的生殖毒性效应,选用雄性昆明鼠16只,分成4组,采用腹腔注射染毒的方法,各组浓度分别为2 mg/kg(低)、20 mg/kg(中)和200 mg/kg(高),给药量为每只鼠0.1 mL,对照组腹腔注射等体积的生理盐水,每天上午10:00注射1次,持续3周.处死并剖检试验鼠,取其睾丸和附睾处理,计算小鼠睾丸的脏器系数,精子总数及精子存活率,并观察精子畸形数和睾丸组织的病理改变.与对照组比较,随着染毒剂量的增加,睾丸的脏器系数减小,精子总数和存活率明显下降,低剂量组与对照组差异显著(P＜0.05)；中、高剂量组与对照组比较差异极显著(P＜0.01)；中、高剂量组的精子畸形数量显著增多；各染毒组小鼠的睾丸组织均具有明显的病理改变和损伤.说明甲醛对雄性小鼠的生殖器官具有明显的毒害作用.     

As_2O_3对小鼠雄性生殖系统的毒性作用

为了研究三氧化二砷(As_2O_3)对雄性小鼠生殖系统的影响,将40只6周龄雄性小鼠随机分为4组,以0,3,6,9 mg/kg的剂量连续4周皮下注射As_2O_3溶液,观察睾丸和附睾病理变化,检测精子活力、血浆和睾丸中砷含量、睾酮含量、抗氧化指标(MDA、GSH-Px)、生殖相关标志性分子AR、GPx5和Miwi基因表达以及Miwi定位表达。结果显示,As_2O_3处理组中睾丸生精管畸形,管内生精细胞排列紊乱,附睾管内精子和生精细胞显著减少。随着As_2O_3浓度的增加,精子活力下降,血浆和睾丸中的砷含量增加,睾酮水平降低。在血浆和睾丸中,MDA和GSH-Px含量在6和9 mg/kg As_2O_3组显著增加(P0.05)。生殖相关标志性分子AR、GPx5和Miwi的表达量与对照组相比显著降低(P0.05)。Miwi在睾丸初级精母细胞中的定位表达随着As_2O_3剂量的增加明显降低。上述结果表明,As_2O_3诱导小鼠发生氧化应激,阻碍了小鼠的精子成熟和精子发生,导致生殖毒性。     

氧化乐果对雄性小鼠睾丸琥珀酸脱氢酶和精液质量的影响

试验旨在研究有机磷农药氧化乐果对雄性小鼠睾丸琥珀酸脱氢酶(SDH)和精液质量的影响作用。将40只健康昆明雄性小鼠随机分为4组,即低、中、高3个染毒组和对照组,其中染毒组分别灌胃1.0、2.0、4.0 mg/kg氧化乐果,对照组灌胃生理盐水,采用等容量灌胃法(0.2 mL/10 g体重),连续灌胃14 d。随着氧化乐果染毒剂量的逐渐增加,小鼠睾丸琥珀酸脱氢酶(SDH)活力、精子密度、存活率均明显降低,与对照组相比差异显著(P＜0.05);小鼠体重、睾丸重、附睾及其脏器系数与对照组相比差异均不显著(P＞0.05)。氧化乐果对小鼠精子密度和精子存活率有一定的损伤作用,对睾丸琥珀酸脱氢酶有明显的抑制作用。     

菟丝子水提液对环磷酰胺致雄性小鼠生殖损伤的保护作用研究

为了探讨菟丝子水提液对环磷酰胺(CP)所致雄性小鼠生殖损伤的保护作用,试验对SPF级KM雄性小鼠腹腔注射CP制作生殖损伤模型,再将其分为CP对照组及高、中、低剂量菟丝子组,各剂量组小鼠灌胃给予菟丝子水提液,观察菟丝子水提液对CP所致生殖损伤小鼠附睾系数、睾丸系数、精子密度、精子活率、精子活力、精子畸形率、睾丸形态的影响。结果表明:与CP对照组比较,高、中、低剂量菟丝子组均可显著提高小鼠附睾系数、睾丸系数、精子密度、精子活率、精子活力,并降低精子畸形率(P0.05)。同时,与CP对照组相比较,高、中、低剂量菟丝子组小鼠睾丸生精上皮明显变厚,生精细胞和间质细胞数量明显增多,管腔内各级精母细胞和精子细胞明显增多。说明菟丝子水提液对CP所致雄性小鼠生殖损伤具有保护作用。     

三苯基锡对雄性SD大鼠性腺发育的影响

为研究三苯基锡(TPT)对雄性哺乳动物生殖的毒性作用,将20只雄性青春期Sparague Dawley(SD)大鼠随机分为3个不同剂量的试验组(0.5、5、50μg/kg)和1个对照组(生理盐水)。每3d灌胃1次,暴露54d,末次灌胃24h后用100g/L水合氯醛麻醉并处死大鼠,取其睾丸和附睾。采用石蜡切片和HE染色方法观察睾丸和附睾组织学;采用分光光度法测定睾丸中碱性磷酸酶(AKP)、总抗氧化能力(TAOC)和γ-谷氨酰转肽酶(γ-GT)水平。结果显示,大鼠睾丸内曲精小管直径随药物剂量的增加而减小,曲精小管生精细胞和管腔内精子数量均有不同程度减少;低、中剂量组AKP高于对照组,高剂量组低于对照组,但差异不显著(P0.05);低剂量组γ-GT活力和T-AOC显著高于对照组,中剂量组与对照组相比变化不明显,高剂量组显著低于对照组(P0.05)。试验证实了TPT在一定程度上影响了雄性大鼠性腺生长发育与精子发生,推测TPT对雄性哺乳动物具有生殖毒性。     

玉米赤霉烯酮对雄性小鼠生殖系统的毒性作用

为探讨玉米赤霉烯酮(ZEA)对雄性生殖系统的毒性作用,本试验选取清洁级昆明系雄性小鼠93只,随机分成5组:25 mg/kg、50 mg/kg、75 mg/kg ZEA处理组、溶剂对照组(DMSO)、空白对照组(生理盐水),进行腹腔注射染毒,每天1次,连续5 d,于末次染毒后第2天摘眼球采血并脱颈处死动物,分离睾丸和附睾,测定脏器系数、精子密度和活力,睾丸酶的活力水平以及血清睾酮和雌激素的浓度。结果显示,与对照组相比,玉米赤霉烯酮显著地降低小鼠的体重和精液品质,睾丸乳酸脱氢酶(LDH)、碱性磷酸酶(AKP)、酸性磷酸酶(ACP)的活力随着染毒剂量的增加显著升高(P0.01,P0.05),血清睾酮和雌激素浓度随染毒剂量的增加显著下降(P0.01,P0.05)。该结果提示,玉米赤霉烯酮对雄性小鼠生殖系统具有严重的损伤作用,影响生精功能。     

Effects of exposure to genistein during pubertal development on the reproductive system of male mice

Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may affect adversely the development of the male reproductive system. Twenty-one days old ICR mice weaned from dams fed with a casein-based AIN-76A diet during gestation and lactation were exposed to genistein (2.5 and 5.0 mg/kg/day, p.o.) for 5 weeks. 17beta-Estradiol (7.5 microg/kg/day) and corn oil were used for the positive and negative vehicle controls, respectively. The animals were fed the casein-based AIN-76A diet throughout the experiment. There were no significant differences in body weights of mice between the genistein groups and the negative control group. No significant differences in relative reproductive organ weights were found among all experimental groups. Sperm counts in epididymis and testes were slightly decreased in the genistein-exposed groups compared with control group. Sperm motile characteristics in genistein-exposed groups were slightly higher than those of the control group. Levels of phospholipid hydroxide glutathione peroxidase mRNA in the testis, epididymis, and prostate of mice exposed to genistein or estradiol were significantly higher than those of the controls (P<0.05). Exposure to genistein caused hyperplasia of Leydig cells in the testis and a slight increase of interstitial fibroblasts in the epididymis, while estradiol treatment caused severe damage to the testis and epididymis. These results suggest that dietary uptake of genistein during the juvenile period may affect male reproductive development, resulting in a slight decrease in sperm count, but with an increase in sperm motion quality.     

Reproductive disorders in pubertal and adult phase of the male rats exposed to vinclozolin during puberty

Vinclozolin (VCZ) is a systemic dicarboximide fungicide with antiandrogenic activity. Reproductive toxicity of VCZ was investigated in male rats exposed to VCZ during puberty. Sprague-Dawley male rats aged with 35 days were assigned to six different groups; negative control, positive control receiving flutamide (100 mg/kg), VCZ (100, 200 and 400 mg/kg), and a combination of VCZ (200 mg/kg) + methyltestosterone (100 mg/kg). The animals were treated with test compounds by oral gavage daily during 35 to 44 days of age. In pubertal rats sacrificed on the next day after final treatment, VCZ or flutamide-treated group showed a decrease in weights of prostate, epididymis, and seminal vesicle, hypertrophy of Leydig cells in the testis, detached debris and sloughed cells in the tubules of the caput epididymis, and an increase in serum testosterone levels. On the other hand, combined treatment of VCZ + methyltestosterone decreased testicular weight, increased seminal vesicle weight, and induced degeneration of spermatocytes. In adult rats sacrificed at five weeks after final treatment, flutamide decreased testicular sperm counts, and VCZ, flutamide and VCZ + methyltestosterone also decreased epididymal sperm counts. In addition, treatment of VCZ (400 mg) or VCZ + methyltestosterone decreased some motion kinematic parameters of sperms including curvilinear velocity, mean angular displacement and lateral head displacement. Flutamide treatment also decreased lateral head displacement. These results indicate that VCZ exposure during pubertal period in male rats causes reproductive disorders in puberty and adulthood.     

Ivermectin effects on motor coordination and contractions of isolated rat diaphragm

Ivermectin, the antiparasitic drug from the macrocyclic lactones class raises attention due to its high efficiency against nematodes and arthropods and very specific toxic and side effects that it may produce in host. Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality. In our study increasing intravenous doses of ivermectin, (6 or more times higher than therapeutic dose: 1.25, 2.5, 3.75, 5.0, 6.25 and 7.5 mg/kg), caused dose-dependent disturbance of motor coordination in treated rats. The median effective dose (ED50) that was able to impair the rota-rod performance in rats treated 3 min before testing was 2.52 mg/kg. This effect weakens over time, while in the rats treated 60 min before the rota-rod test, ED50 of ivermectin was 4.21 mg/kg. Whereas, all tested doses of ivermectin did not cause any other clinical symptoms of toxicity. Ivermectin has no effect on the contractions of isolated diaphragm caused by the EFS, which effectively blocked mecamylamine (100 μM) and pancuronium (1 and 2 μM). Effect on motor coordination is the first detectable clinical symptom of ivermectin toxicity and apparently is a result of its central effects.     

氟对雄性小鼠生长发育及性腺中氟含量的影响

本试验旨在研究氟对性成熟期雄性小鼠生长发育及性腺中氟含量的影响。将40只健康昆明雄性小鼠随机分为4组,即低、中、高3个染氟组和对照组,其中染氟组分别饮水摄入氟化钠30、70和150 mg/L,对照组饮用蒸馏水,染氟期间,观察动物的一般状况,每周记录小鼠体重,49 d后,收集血液、股骨、睾丸、附睾和精囊腺,测定其氟含量。与对照组相比,各染氟组体重均无显著差异(P＞0.05),高氟组小鼠体增重显著低于对照组(P＜0.05);各染氟组股骨氟含量均显著高于对照组(P＜0.05),睾丸和附睾中氟含量随摄氟剂量的增加呈剂量依赖性,且高氟组显著升高(P＜0.05),血清与精囊腺中氟含量与对照组相比无显著差异(P＞0.05)。结果表明,高氟对性成熟期雄性小鼠生长发育有抑制作用,且突破了血睾屏障和血-附睾屏障进而对生殖系统产生影响。     

Protective Effect of Sulforaphane on Reproductive Function of Male Mice with Cadmium Poisoning

The study was aimed to explore the protective effect of sulforaphane (SFN) on the reproductive function of male mice with cadmium poisoning.40 healthy clean grade male Kunming mice were randomly divided into four groups:control group (H₂O),cadmium chloride group (2.3 mg/kg CdCl₂),sulforaphane group (10 mg/kg SFN),sulforaphane + cadmium chloride group (10 mg/kg SFN+2.3 mg/kg CdCl₂),and continuous administration for 10 d,all mice were executed by dislocated cervical vertebra at 2 d after the last administration,and then the pathologic changes of testicular tissues,organ coefficient of testicle and epididymis,sperm quality and concentration of testosterone were tested.Additionally,the contents of GSH and MDA,and the activities of T-SOD in testis were also detected at the same time. Compared with the control group,pathology damages were observed in cadmium chloride group,organ coefficient of testis and epididymis,sperm quality and levels of testosterone extremely significantly decreased (P<0.01),the activities of T-SOD and GSH content were extremely significantly decreased (P<0.01),and the concentration of MDA was extremely significantly enhanced (P<0.01).Compared with the control group,the activity of T-SOD and concentration of GSH in sulforaphane group were significantly increased (P<0.05),and the concentration of MDA was not significant different between the control group and sulforaphane group (P>0.05).While compared with the cadmium chloride group,the sperm motility rate and sperm total count in sulforaphane and cadmium chloride group were extremely significantly increased (P<0.01),the organ coefficient of testicle and epididymis was increased significantly (P<0.05),the concentration of GSH and activity of T-SOD in testicular tissue were extremely significantly increased (P<0.01),and the concentration of MDA was extremely significantly decreased (P<0.01).The results indicated that sulforaphane had the protection effect on reproduction function of male mice with cadmium poisoning.     

莱菔硫烷对镉中毒雄性小鼠生殖机能保护作用的研究

本试验旨在研究莱菔硫烷(SFN)对染镉雄性小鼠生殖机能的保护作用.选择健康的清洁级雄性昆明系小鼠40只,随机分成4组,分别为对照组(H₂O)、镉组(2.3 mg/kg CdCl₂)、莱菔硫烷组(10 mg/kg SFN)、镉+莱菔硫烷组(10 mg/kg SFN+2.3 mg/kg CdCl₂),连续给药10 d,于最后一次给药2 d后脱颈处死,检测小鼠睾丸组织病理学变化、小鼠睾丸及附睾的脏器系数、精液品质及血清睾酮浓度.同时检测睾丸组织内丙二醛(MDA)、谷胱甘肽(GSH)含量及总超氧化物歧化酶(T-SOD)活性的变化.结果表明,与对照组相比,镉组小鼠的睾丸组织发生病理学损伤,睾丸及附睾的脏器系数、精液品质及血清睾酮浓度均极显著降低(P<0.01),睾丸组织T-SOD活性、GSH含量也极显著降低(P<0.01),MDA含量极显著提高(P<0.01);莱菔硫烷组T-SOD活性和GSH含量显著升高(P<0.05),MDA含量与对照组相比差异不显著(P>0.05).与镉组相比,镉+莱菔硫烷组小鼠的精子活率、精子总数极显著增加(P<0.01),睾丸与附睾的脏器系数显著增加(P<0.05),小鼠睾丸组织GSH含量、T-SOD活性极显著提高(P<0.01),MDA含量极显著降低(P<0.01).以上结果指出莱菔硫烷对镉中毒雄性小鼠的生殖机能具有保护作用.     

Central and peripheral neurotoxic effects of ivermectin in rats

Ivermectin is considered a very safe drug; however, there are reports of toxic effects in particularly sensitive populations or due to accidental overdose. The aim of this study was (1) to further characterize the central and peripheral toxic effects of ivermectin in animals and (2) to determine possible therapeutic strategies for use in cases of ivermectin poisoning. We tested the effects of experimental doses of ivermectin previously reported to cause various intensities of CNS depression. However, in our study, ivermectin at 2.5, 5.0 and 7.5 mg/kg i.v. did not produce visible CNS depression in rats and 10 mg/kg resulted in sleepiness and staggering 10 to 40 min after application, while a dose of 15 mg/kg caused CNS depression very similar to general anesthesia. Ivermectin dose-dependently potentiates thiopentone-induced sleeping time in rats. Flumazenil (0.2 mg/kg), the benzodiazepine antagonist, did not affect the action of thiopentone; however, it significantly reduced sleeping time in rats treated with a combination of ivermectin (10 mg/kg) and thiopentone (25 mg/kg; from 189.86 ± 45.28 min to 83.13 ± 32.22 min; mean ± SD). Ivermectin causes an increase in the tonus (EC(50)=50.18 μM) and contraction amplitude (EC(50)=59.32 μM) of isolated guinea pig ileum, very similar to GABA, but without the initial relaxation period. These effects are dose-dependent and sensitive to atropine. Our results confirm the central and peripheral GABAergic properties of ivermectin in mammals and also indicate involvement of the cholinergic system in its toxicity. In addition, the results suggest that flumazenil and atropine have potential clinical roles in the treatment of ivermectin toxicity.     

Effects of exposure to genistein and estradiol on reproductive development in immature male mice weaned from dams adapted to a soy-based commercial diet

Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may adversely affect the development of male reproductive system. Twenty one-day-old ICR mice weaned from dams fed with a soybean-based diet throughout gestation and lactation were exposed by gavage to genistein (2.5 mg/kg b.w./day) or 17beta-estradiol (7.5 microg/kg b.w./day) for five weeks. Corn oil was used as a negative control. The animals were fed with a casein-based AIN-76A diet throughout the experimental periods. There were no significant differences in body and organ weights of mice among experimental groups. No significant differences in sperm counts and sperm motile characteristics were found between control and genistein groups. Treatment of 17beta-estradiol caused a significant decrease in prostate weight and epididymal sperm counts compared to the control (p<0.05). The levels of phospholipid hydroxide glutathione peroxidase in the testis and prostate of mice exposed to genistein or 17beta-estradiol were significantly higher than that of the control mice (p<0.05). 17beta-estradiol treatment caused degeneration and apoptosis of germ cells in the testis, depletion and degeneration in the epididymal epithelium, and hyperplasia of mucosal fold region in the prostate of mice. Genistein treatment did not cause any lesion in the testis, epididymis, and prostate. These results suggest that dietary uptake of genistein during juvenile period may not affect male reproductive development and functions.     

Ivermectin effects on motor coordination and contractions of isolated rat diaphragm

Ivermectin, the antiparasitic drug from the macrocyclic lactones class raises attention due to its high efficiency against nematodes and arthropods and very specific toxic and side effects that it may produce in host. Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality. In our study increasing intravenous doses of ivermectin, (6 or more times higher than therapeutic dose: 1.25, 2.5, 3.75, 5.0, 6.25 and 7.5 mg/kg), caused dose-dependent disturbance of motor coordination in treated rats. The median effective dose (ED50) that was able to impair the rota-rod performance in rats treated 3 min before testing was 2.52 mg/kg. This effect weakens over time, while in the rats treated 60 min before the rota-rod test, ED50 of ivermectin was 4.21 mg/kg. Whereas, all tested doses of ivermectin did not cause any other clinical symptoms of toxicity. Ivermectin has no effect on the contractions of isolated diaphragm caused by the EFS, which effectively blocked mecamylamine (100 μM) and pancuronium (1 and 2 μM). Effect on motor coordination is the first detectable clinical symptom of ivermectin toxicity and apparently is a result of its central effects.