孕期二月桂酸二丁基锡暴露对子代大鼠睾丸酶活力和生精功能的影响

目的 探讨孕期接触二月桂酸二丁基锡(DBTD)对Wistar大鼠子代雄性鼠性成熟后睾丸酶活力和生精功能的影响.方法 以0、10、20和30 mg/kg剂量的DBTD溶液对妊娠第12天的Wistar孕鼠连续灌胃染毒至第20天,仔鼠出生后第70天,每组随机抽取10只雄性大鼠,称重并处死,测定睾丸脏器系数、附睾精子数,并采用分光光度法测定睾丸酶活力.结果 各剂量组孕鼠染毒期间体重增加量、产仔数、仔鼠雌雄比例及子代雄性大鼠体重与对照组比较,差异均无统计学意义(P＞0.05);30 mg/kg组睾丸重量和睾丸脏器系数高于对照组,差异有统计学意义(P＜0.01,P＜0.05);20和30 mg/kg组精子数高于对照组,差异有统计学意义(P＜0.05,P＜0.01).各剂量组琥珀酸脱氢酶(SDH)活力和一氧化氮合酶(NOS)活力与对照组比较,差异无统计学意义(P＞0.05);10和20 mg/kg组酸性磷酸酶(ACP)活力、10 mg/kg组乳酸脱氢酶(LDH)活力、30 mg/kg组一氧化氮(N0)含量均高于对照组,差异有统计学意义(P＜0.05).结论 在本实验染毒时间和剂量范围内,DBTD对子代雄性大鼠睾丸发育和精子形成有促进作用,而对睾丸酶活力无直接影响.     

孕期三丁基氯化锡染毒对子代雄性大鼠发育及性激素的影响

目的 探讨孕期三丁基氯化锡(TBTC)暴露对子代雄性大鼠发育及性激素的影响.方法 将健康成年SPF级妊娠Wistar大鼠随机分为5.0、2.5、1.0 mg/kg TBTC染毒组和阴性对照组(玉米油),每组4只.从妊娠第12天起,采用经口灌胃方式进行染毒,每天1次,直至妊娠第20天,灌胃剂量为5.0 ml/kg.出生后第70天,每组随机抽取10只雄性仔鼠,称重后断头取血,分离双侧睾丸及附睾组织,称重,计算睾丸和附睾的脏器系数.测定血清中睾酮(T)浓度、黄体生成素(LH)、卵泡刺激素(FSH)水平.结果 各TBTC染毒组孕鼠产仔数及雌雄比例间比较,差异无统计学意义(P＞0.05).与对照组比较,2.5和5.0 mg/kg组雄性仔鼠断乳后体重降低,睾丸的脏器系数升高,差异均有统计学意义(P＜0.01).各TBTC染毒组雄性仔鼠附睾脏器系数间比较,差异无统计学意义(P＞0.05).各TBTC染毒组雄性仔鼠血清中T、LH、FSH浓度间比较,差异均无统计学意义(P＞0.05).结论 在妊娠中后期TBTC染毒对子代雄性大鼠具有内分泌干扰作用,影响其生长发育,但暴露尚未引起雄性仔鼠血清中性激素的变化.

Abstract：

Objective To explore the effects of tributyltin chloride (TBTC) exposure during pregnancy on development and sex hormone level of male offspring Wistar rats. Methods The healthy pregnant Wistar rats were randomly divided into 4 groups, 4 in each group,they were given doses of TBTC (5.0,2.5,1.0 mg/kg) by gavage from days 12-20 of gestation. On postnatal day (PND) 70,10 male offspring rats were randomly selected in each group and sacrificed, the blood samples were collected. The testis and epididymis were weighed for account of organic coefficient. The concentration of testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH) in serum was measured. Results There were no significant differences in number and the sex ratio of offspring rats between the control group and the treatments groups (P>0.05). Compared with the control group, an obvious retarded development was observed from PND21-70 and the viscera coefficient of testis were increased significantly in 2.5 or 5.0 mg/(kg·d) group (P<0.01). No significant difference was observed in serum LH,FSH level. Conclusion TBTC exposure during pregnancy can cause retarded development and increase of organic coefficient of testis of male offspring rats.     

苯并咪唑对大鼠生精功能和睾丸酶活力的影响

目的探讨苯并咪唑对雄性大鼠生精功能和睾丸酶活力的影响。方法将40只清洁级 Wistar 雄性大鼠随机分为低(20mg/kg)、中(100mg/kg)、高(200mg/kg)苯并咪唑剂量组和溶剂对照组,每组10只,各组经口灌胃染毒,灌胃量为0.01 ml/g,对照组给予等量的蒸馏水和吐温80溶液,每天1次,连续80 d。染毒结束后,立即取睾丸和附睾观察其形态,测定各组大鼠体重以及睾丸和附睾重量,并计算睾丸和附睾的脏器系数;测定附睾尾精子数量和精子活动率以及睾丸标志酶的活力。结果对照组和低剂量组大鼠睾丸和附睾呈粉红色,体积大,光滑饱满。高、中剂量组大鼠睾丸和附睾呈紫红色,体积小,萎缩明显。高、中剂量组大鼠睾丸和附睾的脏器系数、精子数量和精子活动率均低于对照组,差异有统计学意义(P<0.01)。高、中剂量组酸性磷酸酶(ACP)和山梨醇脱氢酶(SDH)活力均低于对照组,差异有统计学意义(P<0.05或 P<0.01);且 ACP 和 SDH 活力随着染毒剂量的增加而降低。高剂量组乳酸脱氢酶(LDH)活力低于对照组,差异有统计学意义(P<0.05)。不同组别间葡萄糖-6-磷酸脱氢酶(G-6-PDH)活力比较,差异无统计学意义(P>0.05)。结论苯并咪唑可影响雄性大鼠生精功能,这可能是由于苯并咪唑影响了睾丸组织能量代谢酶导致未成熟生精细胞脱落。     

毒死蜱对大鼠生精功能和睾丸组织酶活力的影响

目的 探讨毒死蜱对雄性大鼠生精功能和睾丸组织酶活力的影响.方法 将40只21日龄SPF级雄性Wister 大鼠随机分为4组,分别为对照组(1 mg/L吐温80溶液)和低剂量(2.7 mr/kg)、中剂量(5.4 mr/kg)、高剂量(12.8 mr/kg)毒死蜱染毒组,每组10只.采用经口灌胃方式进行染毒,染毒容量10...     

孕期母鼠接触三丁基氯化锡对子代雌性大鼠发育和性激素的影响

目的 通过对母鼠进行孕期染毒来检测三丁基氯化锡(TBTC)对子代雌性大鼠的发育毒性和性成熟后生殖系统的影响.方法 选择SPF级3月龄的健康成年Wistar大鼠,按雌:雄为2:1比例同笼配种.取妊娠大鼠16只,随机分为4组(1个对照组和3个处理组),于妊娠第12～20天,将对照、低、中、高剂量组分别按0、1.0、2.5、5.0mg/(kg·d)进行灌胃染毒.将出生后第70天的子代雌性大鼠称重后断头处死,称量肝脏、肾脏、子宫、卵巢的重量,计算脏器系数并做病理切片.采用放射免疫法测量血清中促卵泡激素(FSH)、促黄体生成激素(LH)、睾酮(T)、雌二醇(E2)的含量.结果 高、中剂量组体重的增长速度低于对照组,差异均有统计学意义(P＜0.05).高、中剂量组肾脏重量分别低于对照组,高剂量组卵巢重量低于对照组,差异均有统计学意义(P＜0.05).且肝脏、肾脏重量随着染毒剂量的升高而降低.各剂量组肝脏、肾脏、子宫、卵巢的脏器系数间比较,差异均无统计学意义(P＞0.05).高剂量组FSH、E2水平均高于对照组,差异有统计学意义(P＜0.05).各剂量组血清中均未检测出T.各剂量组肝脏、肾脏、子宫、卵巢的组织切片均未见明显的病理学改变.结论 孕期母鼠接触TBTC,可抑制子代雌性大鼠的生长发育,并可引起FSH及E2水平的升高.     

三甲基氯化锡染毒对大鼠肠道推进功能的影响

将24只SD大鼠分为4组,三甲基氯化锡(TMT)组分别给予4.64 mg/kg、10 mg/kg和21.5 mg/kg TMT染毒,对照组给予生理盐水,染毒后24 h测定肠道推进功能和Na+-K+-ATPase活力;另将24只大鼠分为4组,TMT组给予10mg/kg染毒,对照组给予生理盐水,分别在3 d和6 d测定肠道推进功能和Na+-K+-ATPase活力。结果显示,大鼠小肠不同部位的Na+-K+-ATPase活力不同。经TMT染毒后肠道推进率较对照组明显降低(P0.01),中高剂量染毒组的肠道Na+-K+-ATPase活力明显降低(P0.01)。10 mg/kg TMT染毒大鼠3 d和6 d肠道Na+-K+-ATPase活力亦明显下降(P0.05)。提示TMT染毒可能会抑制小肠推进功能,推进率的下降可能与肠道Na+-K+-ATPase活力抑制有关。     

三丁基氯化锡对哺乳动物生殖毒性及作用机制

三丁基锡(tributyltin,TBT)曾主要作为船舶防污油漆广泛使用,后来发现TBT对海洋生物产生严重危害,尤其致软体动物发生性畸变,致使种群退化、数量锐减^[1],于2003年禁用.由于其长期残留性,即使在停用相当长时间后,海水和底泥中仍存在TBT,继而在海洋生物中蓄积,其富集因子大约在5 000-25 000之间,且经蒸煮后仍会存在,提示食用海产品可能存在TBT的潜在危害^[2].三丁基氯化锡(tributyltinchloride,TBTC)是TBT在水中的主要存在形式.因而本文就TBTC对哺乳动物的生殖毒性及其作用机制的研究进展作一综述.     

三甲基氯化锡对亚慢性染毒大鼠肾氢钾ATP酶活力及蛋白与基因表达的研究

目的 探索三甲基氯化锡(trimethyltin chloride,TMT)对亚慢性染毒大鼠肾氢钾ATP酶活力、蛋白和基因表达水平的影响.方法 取6周龄雌性SD大鼠55只,随机分成对照、低剂量、中剂量、高剂量和超高剂量组,共5组,每组11只,分别按0、8.20、32.81、131.25、262.50μg·kg-1·d-1的TMT剂量经饮水亚慢性染毒,14周后测定血钾水平,取大鼠肾脏,用定磷法测量氢钾ATP活力,用免疫印迹法测定肾氢钾ATP酶蛋白表达水平,用实时定量-聚合酶链反应法测定肾氢钾ATP酶的mRNA表达水平.结果 与对照组[(6.9±0.3)mmol/L]比较,超高剂量组血钾水平[(5.6±0.4)mmol/L]明显降低,差异有统计学意义(P＜.01).低剂量和超高剂量组氢钾ATP酶活力分别为(4.50±1.45)、(435±-0.72)μmolPi·mgprot-1·h-1,明显低于对照组[(6.55±0.77)μmolPi·mgprot-1·h-1],差异有统计学意义(P＜0.05).与对照组比较,超高剂量组氢钾ATP酶蛋白和mRNA表达水平差异均无统计学意义(P＞0.05).结论 TMT亚慢性接触可抑制氢钾ATP酶的活力,但不抑制该酶的蛋白和基冈表达.

Abstract：

Objective To study the activity、protein and gene expression of renal HK-ATPase (HKA) in rats subchronicly exposed to trimethyltin chloride (TMT). Methods In subchronic toxic test (14-week), 55 female SD rats (age, 6 weeks) were divided randomly into 5 groups: control, low, medium, high and super high dosage, respectively, which drank water with TMT of 0, 8.20, 32.81, 131.25 and 262.50 μg·kg-1 ·d-1 for 14 weeks.Then serum K+ levels were measured; the activities of H K-ATPase (HKA) in kidneys were detected by the method of determinenate phosphorus content;Western Blot assay and real-time PCR were used to exam the protein and mRNA expression levels of HKA in kidneys, respectively. Results The serum K + level in super-high dosage group was (5.6±0.4) mmol/L, which was significantly lower than that [(6.9±0.3) mmol/L] in control group (P＜0.01).The HKA enzymatic activity of kidneys in low and super high dosage groups was 4.50±1.45 and 4.55±0.72 μmolPi·mg prot-1h-1, respectively, which were significantly lower than that (6.55±0.77 μmol Pi ·mg prot-1h-1) in control group (P＜0.05). Conclusion When rats were exposed subchronicly to TMT, the renal HKA activity could reduce, but the expression levels of HKA protein and mRNA did not decrease.     

氯化三丁基锡对大鼠睾丸支持细胞的影响

[目的]探讨氯化三丁基锡对雄性sD大鼠睾丸支持细胞活力和增殖的影响。[方法]无菌制备20-23天龄sD大鼠的睾丸支持细胞,用HE染色、FAS—L免疫组化染色进行细胞鉴定。设空白对照组、溶剂对照组和20×10^-9、40×10^-9、80×10^—9、120×10^—9mol／L氯化三丁基锡染毒组,用四唑盐比色法（MTT）、免疫细胞化学法观察细胞增殖及增殖细胞核抗原（PCNA）的表达情况,流式细胞仪分析细胞周期分布。[结果]各染毒组睾丸支持细胞的存活率明显低于对照组（P〈0．05）,G0／G1期细胞构成比增加,细胞增殖指数下降,80×10^-9、120×10^-9mol／L染毒组PCNA表达量下降。[结论]氯化三丁基锡可通过抑制睾丸支持细胞增殖,影响细胞周期分布和PCNA表达而表现出对雄性大鼠的生殖毒性。     

三甲基氯化锡对亚慢性染毒大鼠肾氢钾ATP酶活力及蛋白与基因表达的研究

Objective To study the activity、protein and gene expression of renal HK-ATPase (HKA) in rats subchronicly exposed to trimethyltin chloride (TMT). Methods In subchronic toxic test (14-week), 55 female SD rats (age, 6 weeks) were divided randomly into 5 groups: control, low, medium, high and super high dosage, respectively, which drank water with TMT of 0, 8.20, 32.81, 131.25 and 262.50 μg·kg-1 ·d-1 for 14 weeks.Then serum K+ levels were measured; the activities of H K-ATPase (HKA) in kidneys were detected by the method of determinenate phosphorus content;Western Blot assay and real-time PCR were used to exam the protein and mRNA expression levels of HKA in kidneys, respectively. Results The serum K + level in super-high dosage group was (5.6±0.4) mmol/L, which was significantly lower than that [(6.9±0.3) mmol/L] in control group (P＜0.01).The HKA enzymatic activity of kidneys in low and super high dosage groups was 4.50±1.45 and 4.55±0.72 μmolPi·mg prot-1h-1, respectively, which were significantly lower than that (6.55±0.77 μmol Pi ·mg prot-1h-1) in control group (P＜0.05). Conclusion When rats were exposed subchronicly to TMT, the renal HKA activity could reduce, but the expression levels of HKA protein and mRNA did not decrease.     

Effects of Iron Supplementation on Testicular Function and Spermatogenesis of Iron-Deficient Rats

Iron deficiency is the most common micronutrient deficiency in the world. Previous studies have shown that iron deficiency increases oxidative stress and decreases antioxidant enzymes, and studies of male infertility indicated that oxidative stress may affect male reproductive functions. The aim of this study was to investigate the effects of iron supplementation on spermatogenesis and testicular functions in iron-deficient rats. Three-week-old male Sprague Dawley (SD) rats were randomly divided into two groups: an iron-adequate control (AI group, 35 ppm FeSO₄) and an iron-deficient group (ID group, <5 ppm FeSO₄). After three weeks, the iron-deficient group was divided into an original iron-deficient group and five iron-supplemented groups, the latter fed diets containing different doses of FeSO₄ (6, 12, 18, 24, and 35 ppm). After five weeks, blood and testis tissue were analyzed. We presented as median (interquartile range, IQR) for continuous measurements and compared their differences using the Kruskal–Wallis test followed by the Mann–Whitney U test among groups. The results showed that as compared with the AI group, the ID group had significantly lower serum testosterone and poorer spermatogenesis (The medians (QR) were 187.4 (185.6–190.8) of AI group vs. 87.5 (85.7–90.4) of ID group in serum testosterone, p < 0.05; 9.3 (8.8–10.6) of AI group vs. 4.9 (3.4–5.4) of ID group in mean testicular biopsy score (MTBS], p < 0.05); iron supplementation reversed the impairment of testis tissue. In the testosterone biosynthesis pathway, iron supplementation improved the lowered protein expressions of hydroxysteroid dehydrogenases caused by iron deficiency. Additionally, decreased activities of glutathione peroxidase and catalase, and increased cleaved-caspase 8 and caspase 3 expression, were found in the iron-deficient rats. The iron-supplemented rats that received > 12 ppm FeSO₄ exhibited improvements in antioxidant levels. In conclusion, iron supplementation can abrogate testis dysfunction due to iron deficiency through regulation of the testicular antioxidant capacity.     

大鼠围产期染毒二苯氯胂对仔鼠存活率和生殖功能的影响

目的 研究大鼠围产期二苯氯胂染毒对仔鼠存活率及生殖功能的影响.方法 选择健康Wistar大鼠(雌性100只,雄性50只),按雌、雄2:1合笼交配,将孕鼠随机分为4组(阴性对照组,0.63、0.94、1.89 mg/kg二苯氯胂染毒组).F0代大鼠妊娠15 d至哺乳28 d连续灌胃染毒.染毒后,观察F0代孕鼠的一般状态、体重变化和F1代仔鼠的一般状态、体重变化、存活情况及生殖功能有无异常.结果 0.94和1.89 mg/kg组F0代母鼠体重分别于哺乳期的10和4 d开始低于阴性对照组,差异有统计学意义(P＜0.05,P＜0.01).0.94和1.89 mg/kg组F1代仔鼠出生4 d的存活率低于阴性对照组,差异有统计学意义(P＜0.05,P＜0.01),1.89 mg/kg组F1代仔鼠出生28 d的存活率低于阴性对照组,差异有统计学意义(P＜0.01).0.94和1.89 mg/kg组F1代孕鼠的吸收胎率高于阴性对照组,差异有统计学意义(P＜0.05).结论 F0代大鼠围产期暴露于二苯氯胂中,当二苯氯胂剂量等于或大于0.94 mg/kg时可对F1代雌性大鼠生殖能力产生影响.     

氯化三丁基锡对雄性小鼠睾酮和雌二醇水平的影响

目的探讨不同剂量氯化三丁基锡(TBTCl)对小鼠雌二醇(E2)、睾酮(T)水平的影响。方法将40只24日龄健康雄性SPF级昆明小鼠按体重随机分为4组,分别为1、0.1、0.01 mg/kg TBTCl染毒组和对照(玉米油)组,每组10只。采用腹腔注射方式染毒,每3天染毒1次,连续染毒25 d,染毒容量为10 ml/kg。观察包皮分离时间和体重变化,检测其血清、睾丸内T、E2水平,并对肝脏内脂肪滴进行病理学观察。结果与0.01 mg/kg TBTCl染毒组比较,对照组和1 mg/kg TBTCl染毒组小鼠体重均较低,差异有统计学意义(P0.05)。TBTCl染毒组与对照组小鼠包皮分离时间比较,差异无统计学意义。与对照组比较,1 mg/kg TBTCl染毒组小鼠血清和睾丸内T水平中位数均较低,0.01 mg/kg TBTCl染毒组小鼠睾丸内E2水平较低,差异有统计学意义(P0.05或P0.01)。而小鼠血清E2水平全部低于所用试剂盒的检测限(11 pg/ml)。TBTCl染毒未能导致小鼠肝脏内脂肪滴明显增加。结论 TBTCl暴露可导致小鼠睾酮和雌二醇水平降低,而不同剂量的TBTCl对小鼠的靶作用位点可能不同,导致对暴露小鼠体重的影响呈非单调性剂量-反应关系。     

Fertility and Hormonal Function in Patients with a Nonseminomatous Tumor of the Testis

Semen quality and serum testosterone, LH, and FSH levels were studied in 54 patients with a unilateral nonseminomatous tumor of the testis-14 before and 40 after orchiectomy.

Semen analyses before and after orchiectomy gave essentially no different results: a poor semen quality was found in most men. The additional effect of a recent orchiectomy on semen quality was not demonstrable in the patients described here.

Before orchiectomy, increased testosterone levels were found in patients with a β-hCG-producing tumor. After orchiectomy serum testosterone levels were decreased, and LH and FSH levels increased. With β-hCG-producing tumors FSH was suppressed after orchiectomy, and testosterone levels did not exceed those in patients with a tumor not producing β-hCG.

The results of semen analysis and of hormonal studies after orchiectomy suggest a dysfunction of the remaining “normal” testis. Diminished spermatogenesis and insufficient testosterone production by the Leydig cells clearly indicate anomalies already present before orchiectomy.     

硒对氟致大鼠睾丸和附睾损害拮抗作用的研究

目的 研究和探讨硒对氟致雄性大鼠生殖损害的拮抗作用及其机理,找出硒对氟毒性的最佳拮抗剂量.方法 给雄性大鼠饮用含氟化钠(150mg/L)及同时分别加入不同浓度亚硒酸钠(0.5,2.0和4.0mg/L)的饮水共8周,观察氟及氟硒联合对大鼠血、尿氟水平及对睾丸和附睾的影响.结果 氟暴露大鼠血液和尿液氟浓度明显升高,血清和睾丸微量元素含量异常、睾丸和附睾组织脂质过氧化物(LPO)含量增加、谷胱甘肽过氧化物酶(GSH-Px)和ATP酶活性显著降低.2.0mg/L亚硒酸钠对大鼠尿氟排泄具有显著促进作用,对氟致血清和睾丸微量元素异常改变具有一定调整作用,对氟致睾丸和附睾LPO含量升高及GSH-Px和ATP酶活性降低具有显著拮抗作用,而0.5和4.0mg/L亚硒酸钠的作用较弱.结论 2.0mg/L亚硒酸钠是本实验条件下硒拮抗氟致睾丸和附睾损害的最佳剂量.