早孕期补充戊酸雌二醇对雄性子代大鼠生殖系统发育的影响

目的:建立大鼠早孕期戊酸雌二醇用药模型,从肛门生殖器距离(AGD)、附睾、睾丸组织发育等方面评估戊酸雌二醇对雄性子代生殖系统发育的影响。方法:妊娠SD大鼠随机分对照组及低、中、高剂量组,孕6～15d每天分别给予戊酸雌二醇0、0.2、0.5、0.8mg/kg灌胃,分娩后正常喂养其雄性子代,出生3d、出生21d分别测量雄性子代AGD,出生60d测量附睾、睾丸的脏器系数(附睾、睾丸重量g/大鼠体重100g),进行睾丸组织学切片观察生精小管的形态学变化,测量生精小管直径和上皮高度。结果:对照组及各给药组雄性子代出生3d、出生21d的AGD比较,无明显差异(P>0.05);对照组及各给药组子代出生60d的附睾、睾丸脏器系数比较、睾丸生精小管直径及上皮高度比较,均无明显差异(P>0.05)。结论:早孕期大鼠补充一定剂量(0.2～0.8mg/kg)戊酸雌二醇,出生的雄性子代在生殖系统发育上未受明显影响,性成熟期的睾丸组织学未见明显改变。     

戊酸雌二醇对子代大鼠性成熟期睾丸功能的影响

目的从睾丸组织发育、附睾精子质量、内分泌激素等方面评估睾丸功能在早孕期给予SD大鼠戊酸雌二醇对其雄性子代性成熟期的影响。方法孕鼠随机分对照组及低、中、高剂量组，孕6～15d灌胃给予戊酸雌二醇0．2～0．8mg／（kg·d），分娩后对其雄性子代性成熟期测定附睾精子密度、活率，睾丸组织学切片观察生精小管的形态学变化，测定血清卵泡刺激素（FSH）、黄体生成素（LH）、睾酮（T）水平。结果对照组及各给药组子代性成熟期的睾丸生精小管直径及上皮高度比较，血清FSH、LH、T比较，无显著差异（P〉0．05）。子代出生60d附睾精子密度低、中、高给药组比较，无显著差异（P〉0．05），但各给药组与对照组比较均显著下降（P〈0．01）。对照组及各给药组子代出生60d的附睾精子活率比较，无显著差异（P〉0．05）。结论早孕期大鼠补充戊酸雌二醇0．2～0．8mg／（kg·d），出生的雄性子代在性成熟期的睾丸功能未见明显缺陷，但可导致精子密度下降，未见剂量依赖关系，提示为避免子代生殖缺陷，仍需在用药剂量上加以限制。     

大豆异黄酮对不同时期子代雄性大鼠生殖性状及ER-β受体表达的影响

目的:研究大豆异黄酮孕期和出生后暴露对子代雄性大鼠生殖系统发育相关指标以及ER-β受体表达的影响。方法:SD大鼠随机分为对照组(玉米油)、大豆异黄酮50、200、400 mg/kg体重和已烯雌酚(DES)0.1 mg/kg体重组,母鼠从妊娠0 d开始灌胃各组药品,子鼠21 d断奶后开始灌胃直至处死。子代雄性大鼠每组随机取6只分别在49 d、90 d处死,观察生殖系统发育相关指标并检测睾丸组织ER-β受体表达情况。结果:①对于不同年龄段子代雄鼠,大豆异黄酮各剂量组以及DES组每日平均摄食量均无显著性差异,但49～90日龄子鼠大豆异黄酮200 mg/kg体重、400 mg/kg体重组以及0.1 mg/kg体重DES组的食物利用率显著下降。②大豆异黄酮剂量为50 mg/kg体重以上时,不同年龄段的子鼠体重均显著下降(P<0.05)且90日龄子代雄鼠体重变化大于49日龄子代雄鼠。③随着大豆异黄酮剂量的增加,睾丸重量、睾丸精子头计数和每日精子生成量呈显著下降趋势且90日龄子鼠以上指标的变化比49日龄子代雄鼠变化更加明显。④随着大豆异黄酮剂量的增加,不同年龄段子代雄鼠各剂量组ER-β受体表达与对照组比较均呈上升趋势且90日龄子代雄鼠上升趋势大于49日龄子代雄鼠。结论:大豆异黄酮孕期和出生后暴露可干扰子鼠雄性生殖系统的发育,ER-β受体表达变化可能是其机制之一。     

青春期前邻苯二甲酸二丁酯持续暴露对大鼠睾丸发育的影响

目的:研究青春期前邻苯二甲酸二丁酯(DBP)持续暴露对睾丸发育的影响。方法:21日龄断乳青春期前雄性SD大鼠随机分为对照组(n=24)和实验组(n=54),每日分别用玉米油或DBP玉米油溶液灌胃,DBP暴露剂量分别为50mg/(kg.d)(低剂量组,n=18)、200mg/(kg.d)(中剂量组,n=18)和600mg/(kg.d)(高剂量组,n=18),各组动物持续暴露14、21、28d后(即PND35,PND42和PND49)断颈处死。记录大鼠体重变化,检测睾丸重量和体积、附属性器官重量及附睾精子,化学发光免疫分析法检测血清睾酮含量,苏木精-伊红染色观察睾丸组织形态学变化,测量生精小管平均直径及进行睾丸活检评分。结果:低剂量组PND35少量生精小管生精细胞排列紊乱,PND42和PND49睾丸、附属性器官发育及生精功能正常;中剂量组PND35和PND42生精细胞排列紊乱、数目减少,PND49生精小管内可见各级生精细胞及精子,睾丸未见萎缩,附属性器官发育正常;高剂量组大鼠体重增长减缓,血清睾酮水平低下,睾丸生精小管变性萎缩,生精上皮发育阻滞,生精细胞大量凋亡坏死,青春期大鼠睾丸萎缩,无精子,附睾、前列腺和精囊等附属性器官发育迟缓。结论:青春期前DBP持续暴露可损害睾丸组织发育和正常生精功能形成,其毒性效应具有剂量依赖性,高剂量DBP持续暴露引起的睾丸毒性在青春期前发育过程中不可修复,而低中剂量暴露引起的睾丸毒性在PND49之前可完全或部分逆转性恢复。     

十八味中药组方对恢复生殖系统损害雄性大鼠模型的作用研究

目的研究十八味中药组方对生殖系统损害不育大鼠模型作用的靶器官和作用机理。方法采用雷公藤多甙建立生殖系统损害大白鼠动物模型,观察十八味中药组方对大鼠睾丸、附睾,精囊腺、前列腺等器官脏器系数及组织学影响;对大鼠精子密度、活力、活率及运动速度、运动方式等精子质量影响;对血清黄体生成素、卵泡刺激素、睾酮、皮质醇等激素分泌的影响。结果十八味中药组方显著提高大鼠脏器系数及附睾腺壁管厚度,提高大鼠精子质量,促进生殖激素及皮质醇分泌。结论十八味中药组方可以恢复大鼠模型的生殖系统病理损害。     

邻苯二甲酸二丁酯致尿道下裂大鼠发育异常和阴茎病理学改变研究

目的邻苯二甲酸二丁酯（DBP）孕晚期染毒诱导子代雄鼠尿道下裂发生和探讨DBP致尿道下裂雄鼠发育异常和阴茎病理学改变。方法雌鼠怀孕14～18d，每天分别灌胃给予大豆油（A组），DBP500（B组）、800（C组）、1200（D组）mg／kg体重，分娩后统计仔鼠数和雄仔鼠体重。出生后（PND）7d测量雄仔鼠肛门生殖器距离（AGD），观察尿道下裂发生率和尿道下裂阴茎病理学改变。PND70,对尿道下裂雄仔鼠称重后解剖，评价发育情况。结果C组仔鼠数和雄仔鼠体重明显减少；D组出现孕鼠死亡和零产仔；尿道下裂仅C组发生。发生率为36．5％。PND7，B、C组雄仔鼠AGD和A组相比明显减小。阴茎连续性病理切片显示典型尿道下裂改变。解剖得尿道下裂雄仔鼠肝、肾、前列腺、睾丸、附睾脏器系数与A组相比明显减小，脑垂体脏器系数明显增大。结论800mg／kg体重DBP孕晚期染毒能高诱导雄仔鼠尿道下裂发生，DBP不仅损害雄仔鼠生殖系统，还引起发育异常。     

青春期前己烯雌酚暴露对SD大鼠睾丸发育及功能的影响

目的:研究青春期前己烯雌酚(DES)暴露对SD大鼠睾丸发育及功能的影响。方法:21日龄雄性SD大鼠90只,随机分为DES0.01、0.1、1.0、10.0μg/(kg.d)4个实验组和1个对照组(分别为Da、Db、Dc、Dd和C组,每组n=18)。于青春期前,即出生后第22d(postnatalday22,PND22)～35d(PND35),实验组每日皮下注射相应剂量的DES,共14d,对照组仅注射溶媒(玉米油)。观察各组大鼠睾丸下降时间。于青春期晚期(PND50)、性成熟后(PND64)和成年期(PND130)分3批(每批n=6)处死各组大鼠取材,测定睾丸重量,观察比较睾丸组织形态学变化,分析PND130大鼠附睾尾精子质量。结果:C、Da、Db、Dc和Dd组睾丸下降时间分别为PND26.17±1.94、26.83±1.47、28.68±1.03、33.50±1.87和41.50±2.74,其中Db、Dc和Dd组较C组明显延迟(P<0.05或P<0.01)。PND50时,C、Da、Db、Dc和Dd组单侧睾丸重量分别为(1.38±0.10)、(1.38±0.12)、(1.30±0.14)、(0.86±0.18)g和(0.73±0.27)g,其中Dc和Dd组较C组显著减轻(P<0.01);与C组比较,Db组仅有少数生精小管生精上皮中的细胞数目稍减少,Dc和Dd组生精小管发育较差、生精上皮中细胞数目减少、精子发生阻滞、间质细胞发育幼稚,其程度随DES暴露剂量增加而加重。PND64时,C、Da、Db、Dc和Dd组单侧睾丸重量分别为(1.60±0.06)、(1.62±0.11)、(1.58±0.08)、(1.47±0.10)g和(0.99±0.37)g,其中Dc和Dd组较C组显著减轻(P<0.05或P<0.01);Dc和Dd组睾丸组织形态学改变与PND50时类似,但总体较PND50有所改善。PND130时,各实验组与对照组比较,单侧睾丸重量差异无统计学意义(P>0.05),睾丸组织形态学改变难以鉴别出明显差异;C、Da、Db、Dc和Dd组大鼠附睾尾精子密度分别为(73.00±16.90)、(68.00±19.67)、(68.67±12.15)、(35.17±15.64)×106/ml和(19.13±5.17)×106/ml,其中Dc和Dd组精子密度较C组明显降低(P<0.01);与C组比较,Dd组精子活动率下降(P<0.01),Db、Dc和Dd组a级精子比例降低(P<0.05或P<0.01),Dd组b级精子比例降低(P<0.01)。结论:青春期前小剂量DES[0.01μg/(kg.d)×14d]暴露对SD大鼠睾丸发育及功能无明显影响,较大剂量DES[1.0～10.0μg/(kg.d)×14d]暴露对大鼠睾丸发育及功能有明显的近期(PND50和PND64)和较远期(PND130)毒性作用,该毒性作用随DES的暴露剂量增加而加重,随鼠龄增长而逐渐减退,其机制可能与间质细胞和支持细胞的发育及功能受损相关。     

青春期己烯雌酚暴露对大鼠睾丸发育及功能的影响

目的 探讨青春期己烯雌酚(diethylstilbestrol,DES)暴露对SD(Sprague-Dawley)大鼠睾丸发育及功能的影响.方法 35日龄雄性SD大鼠90只,随机分为DES 0.01、0.1、1.0、10.0 μg·kg-1·d-14个实验组和1个对照组(编码为Bda、BDb、BDc、BDd和BC组,每组18只).于青春期,即出生后第36天(postnatal day 36,PND 36)至PND 49,实验组每日皮下注射相应剂量的DES,共14 d,对照组仅注射溶媒.于青春期晚期(PND 50)、性成熟后(PND 64)和成年期(PND 130)分3批(每批6只)处死各组大鼠取材,测定睾丸重量,观察比较睾丸组织形态学变化,分析PND 130大鼠附睾尾精子质量.结果 PND 50时,BC、Bda、BDb、BDc和BDd组单侧睾丸重量分别为(1.26±0.13)、(1.23±0.20)、(0.99±0.15)、(0.85±0.23)和(0.60±0.04)g,其中BDb、BDc和BDd组均较BC组减轻(P＜0.05);与BC组比较,BDb组仅有少数生精小管生精上皮中的细胞数目稍减少,BDc和BDd组生精小管发育较差、生精上皮中细胞数目减少、精子发生阻滞、间质细胞发育幼稚,其程度随DES暴露剂量增加而加重.PND 64时,BC、Bda、BDb、BDc和BDd组单侧睾丸重量分别为(1.54±0.14)、(1.55±0.17)、(1.52±0.11)、(1.37±0.14)和(0.88±0.15)g,其中BDc和BDd组均较BC组减轻(P＜0.05);BDc和BDd组睾丸组织形态学改变与PND 50时类似,但较PND 50时有所改善.PND 130时,各实验组与对照组比较,单侧睾丸重量差异无统计学意义(P＞0.05),睾丸组织形态学改变未见明显差异;BC、Bda、BDb、BDc和BDd组大鼠附睾尾精子密度分别为(71.00±14.85)、(69.00±23.98)、(67.00±13.52)、(31.67±12.94)和(18.83±6.68)×106/ml,其中BDc和BDd组精子密度均较BC组明显降低(P＜0.01);与BC组比较,BDd组精子活动率下降(P＜0.01),BDb、BDc和BDd组A级精子比例降低(P＜0.05),BDd组B级精子比例降低(P＜0.01).结论 青春期小剂量DES(0.01μg·kg-1·d-1×14 d)暴露对SD大鼠睾丸发育及功能无明显影响,大剂量DES(1.0～10.0 μg·kg-1·d-1×14 d)暴露对大鼠睾丸发育及功能具有明显的近期(PND 50和PND 64)和较远期(PND 130)毒性作用,该毒性作用随DES暴露剂量增加而加重,随鼠龄增长而逐渐减退,其机制可能与间质细胞和支持细胞的发育及功能受损密切相关.     

维生素E对邻苯二甲酸二异辛酯致雄性大鼠生殖毒性的拮抗作用

目的:探索维生素E(VE)对青春期邻苯二甲酸二异辛酯(DEHP)暴露致雄性大鼠生殖毒性的干预作用以及其机制。方法:将30只35日龄雄性SD大鼠(体重96~122 g)随机分为对照组(玉米油),低[10 mg/(kg·d)]、中[100 mg/(kg·d)]、高[500 mg/(kg·d)]DEHP组,以及VE干预组[(500 mg/(kg·d)DEHP+100 mg/(kg·d)VE],各组给予相应食物30 d。在染毒干预结束后,分别检测大鼠睾丸组织氧化应激指标、附睾尾部精子参数、血清生殖激素水平、凋亡相关靶基因及蛋白的表达。结果:与对照组比较,中、高DEHP组血清中FSH、LH和T水平明显降低,精子运动参数VAP、VCL明显降低,SOD和GSH-Px活力显著降低,Bak、Bax基因表达和Bax/Bcl-2基因表达比值显著升高,细胞色素C mRNA表达及细胞色素C和Caspase-3蛋白表达均显著上调(P均0.05);高DEHP组MDA含量[(3.32±0.87)nmol/mg pro vs(2.13±0.49)nmol/mg pro]明显升高,精子运动参数VAP、VCL、VSL、STR、LIN、WOR均明显降低(P0.05)。与高DEHP组比较,VE干预组的LH和T水平明显升高;VAP、VSL、VCL、STR和WOB明显升高;SOD和GSH-Px活力显著升高;MDA含量明显降低;Bak、Bax基因表达和Bax/Bcl-2基因表达比值显著降低;细胞色素C、Caspase-3 mRNA表达及蛋白表达均显著下调(P均0.05)。结论:青春期DEHP暴露可抑制生殖激素分泌或释放,导致雄性大鼠睾丸组织氧化损伤,激活细胞线粒体凋亡通路,也可导致附睾精子质量下降;而VE对DEHP所诱导的雄性生殖毒性具有一定的拮抗作用。     

邻苯二甲酸二丁酯孕期暴露导致性发育期子代大鼠睾丸细胞凋亡和空泡化

目的:探讨邻苯二甲酸二丁酯(DBP)孕期暴露对性发育期子代大鼠睾丸细胞凋亡的影响。方法:受孕SD大鼠10只,随机分为空白对照组和DBP染毒组,妊娠12~19 d,空白对照组和DBP染毒组分别给予橄榄油1 ml/d和DBP 500 mg/(kg·d)灌胃,于性发育期(PND45)取出睾丸标本,透射电镜观察睾丸细胞结构,HE染色观察各级生精细胞发育情况,TUNEL法检测睾丸细胞凋亡情况,免疫组化和Western印迹观察凋亡调控蛋白Bcl-2、Bcl-XL、Bax和p53的表达。结果:电镜观察见DBP染毒后性发育期子代大鼠睾丸细胞凋亡增加和细胞空泡化,HE染色见各级生精细胞明显减少,TUNEL检测结果显示DBP染毒组细胞凋亡指数明显高于空白对照组(12.00±5.22 vs 3.17±1.47,P0.01),免疫组化和Western印迹提示DBP染毒组促凋亡蛋白Bax和p53的表达较空白对照组显著升高(P0.05)。结论:DBP孕期染毒导致性发育期雄性子代大鼠睾丸生殖细胞和支持细胞凋亡增加及细胞空泡化,促凋亡蛋白Bax和p53的表达明显增高。     

邻苯二甲酸二乙基己酯对新生小鼠睾丸及Leydig细胞影响的实验研究

目的:探讨邻苯二甲酸二乙基己酯(DEHP)对新生小鼠睾丸及Leyd ig细胞形态结构及功能的影响。方法:DEHP分别以低、中、高3组剂量[100、200、500 mg/(kg.d)]灌胃作用于怀孕12 d到产后3 d(GD12~PND3)的KM母鼠,观察DEHP对新生雄性仔鼠体重、睾丸重量、Leyd ig细胞形态结构和3β-羟基类固醇脱氢酶(3-βHSD)活性、酶反应面积的影响。结果:DEHP作用于母鼠后,其雄性子代幼鼠体重和睾丸重量减轻,睾丸Leyd ig细胞形态、超微结构发生改变;高剂量组Leyd ig细胞数量明显增多;低、中剂量组睾酮合成关键酶3β-HSD酶活性下降,酶反应面积减小,但高剂量组在仔鼠出生后15 d时酶活性降低[(吸光度值(0.154±0.011)vs空白对照组(0.222±0.013),P<0.01],而酶反应面积增大[(6 303.0±745.6)μm2vs空白对照组(5 091.4±214.4)μm2,P<0.01)]。结论:DEHP能影响新生雄性小鼠体重、睾丸重量、Leyd ig细胞的形态结构和3β-HSD活性,具有抗雄激素效应。     

Coadministration of active phthalates results in disruption of foetal testicular function in rats

The reproductive effects of the coadministration of di-2-(ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) were studied in both foetal and adult male rat offspring exposed in utero . Pregnant Wistar rats were treated by oral gavage from gestation day 13 to 21 with vehicle control, 150 mg DEHP/kg body weight (bw)/day, 100 mg DBP/kg bw/ or a combination of the two compounds (DEHP 150 + DBP 100 mg/kg bw/day). An additional group of dams received 500 mg DBP/kg bw/day. A significant decrease in foetal testicular testosterone levels was observed in animals exposed to 500 mg DBP/kg/day or the phthalate mixture. Similarly, histological analysis of the foetal testis revealed that the coadministration of DEHP and DBP was able to increase the diameter of seminiferous cords and induce gonocyte multinucleation at doses that individually had no significant effects on these variables. However, in the phthalate mixture group, no significant changes were observed in anogenital distance and nipple retention, variables that are used to indicate possible anti-androgenic effects. Also, the adult endpoints investigated, that included reproductive organ weights and the number of spermatids per testis, were unaffected by any treatment regimen. Overall, coadministration of DEHP and DBP in utero significantly reduced testicular testosterone levels and resulted in misshapen seminiferous cords and gonocyte multinucleation in rat foetal testis. Our results also confirm that these foetal endpoints seem to be the most sensitive markers of prenatal phthalate exposure.     

氰戊菊酯对大鼠精子及生殖激素的影响

目的探讨氰戊菊酯(Fen)对雄性大鼠精子计数、活力以及生殖激素的影响。方法成年雄性SD大鼠,分别以0、20、40、80mg/kg剂量的Fen连续灌胃染毒15和30d,按常规方法进行精子计数和精子活力检测,应用放射免疫法和化学发光免疫法测定大鼠血清卵泡刺激素(FSH)、黄体生成素(LH)、睾酮(T)、雌二醇(E2)和睾丸匀浆中T、E2水平。结果Fen染毒15d时,与0mg/kg组相比,40mg/kg剂量组精子数量明显减少(P<0.01),20和40mg/kg组睾丸匀浆中T水平显著降低(P<0.01,P<0.05),血清LH、FSH水平随染毒剂量的增加而升高,且FSH水平和染毒剂量有显著的剂量-效应关系(P<0.05);Fen染毒至30d时,各组间精子数量差异不显著,与0mg/kg组相比,40mg/kg剂量组(a+b)级精子活力显著降低(P<0.05),血清LH、FSH水平随染毒剂量的增加而升高,但差异不显著。结论Fen对雄性大鼠有明显的生殖毒性作用,能够改变血清和睾丸中的生殖激素水平。     

邻苯二甲酸二-(2-乙基)己酯致小鼠隐睾睾丸和附睾的组织病理学改变

目的 :探讨邻苯二甲酸二 (2 乙基 )己酯 (DEHP)引起的小鼠隐睾睾丸和附睾的组织病理学改变。　方法 :妊娠KM小鼠 4 0只 ,随机分成 5组 ,分别为正常对照组 8只、玉米油对照组 8只、己烯雌酚 (DES)组 8只、DEHP低剂量组 [DEHP 10 0mg/ (kg·d) ]9只和DEHP高剂量组 [DEHP 5 0 0mg/ (kg·d) ]7只。自妊娠第 12d开始到分娩后 3d ,分别持续经口给予DEHP 10 0mg/ (kg·d)、5 0 0mg/ (kg·d)和DES 10 0 μg/ (kg·d)及玉米油 ,观察仔代雄小鼠的隐睾发生率及隐睾睾丸和附睾的组织病理学改变。　结果 :DEHP 5 0 0mg/ (kg·d)组染毒小鼠的隐睾发生率显著增高 ,睾丸和附睾的体积明显减小、重量减轻 ;睾丸生精上皮发育明显异常 ,精曲小管变薄、萎缩 ,间质细胞异常增生 ,电镜下其隐睾精曲小管上皮和间质细胞均出现明显的超微结构改变。同时附睾管腔中的精子数显著减少甚至缺乏。　结论 :高剂量 [5 0 0mg/ (kg·d) ]DEHP可能具有与DES类似的作用 ,是一种诱发隐睾的重要因子。小鼠在孕期及哺乳期接触DEHP后可引起雄性仔鼠性分化异常 ,诱导隐睾发生、睾丸生精上皮损害和生精过程障碍 ,从而对雄性仔鼠生育力产生不利影响。以上作用存在明确的量 效关系。     

Evaluation of spermatogenesis and fertility in F1 male rats after in utero and neonatal exposure to extremely low frequency electromagnetic fields

Aim: To determine whether in utero and neonatal exposure to a 60Hz extremely low frequency electromagnetic field (EMF) results in spermatotoxicity and reproductive dysfunction in the F1 offspring of rats. Methods: Age-matched,pregnant Sprague-Dawley rats were exposed continuously (21h/day) to a 60 Hz EMF at field strengths of 0 (sham control), 5, 83.3 or 500 μT from day 6 of gestation through to day 21 of lactation. The experimentally generated magnetic field was monitored continuously (uninterrupted monitoring over the period of the study) throughout the study. Results: No exposure-related changes were found in exposed or sham-exposed animals with respect to the anogenital distance, preputial separation, testis weight, testicular histology, sperm count, daily sperm production,sperm motility, sperm morphology and reproductive capacity of F1 offspring. Conclusion: Exposure of Sprague-Dawley rats to a 60Hz EMF at field strengths of up to 500μT from day 6 of gestation to day 21 of lactation did not produce any detectable alterations in offspring spermatogenesis and fertility.     

Effects of perfluorooctanoic acid exposure during pregnancy on the reproduction and development of male offspring mice

This study was conducted to explore the effects of maternal exposure to perfluorooctanoic acid (PFOA) on reproduction and development of male offspring mice. Pregnant mice were given 1, 2.5 or 5 mg/kg BW PFOA daily by gavage during gestation. The results showed that the survival number of offspring mice at weaning was significantly decreased. There were no differences in the testicular index of offspring mice between PFOA exposure groups and non‐PFOA group. Maternal exposure to PFOA reduced the level of testosterone in the male offspring mice on PND 21 (p < 0.01) but increased in 1 mg/kg group and decreased in 2.5 and 5 mg/kg groups on PND 70 (p < 0.01). There were different degrees of damage to testis in a dose‐dependent manner, and the number of Leydig cells markedly decreased (p < 0.01) in 2.5 and 5 mg/kg PFOA groups on PND 21 and PND 70. The expression of Dlk1‐Dio3 imprinted gene cluster showed a decreasing trend, where Glt2, Rian and Dio3 gene expressions were significantly reduced (p < 0.05) on PND 21. Therefore, PFOA exposure during pregnancy reduces the number of survival offspring mice, damages testis, disrupts reproductive hormones and reduces the mRNA expressions of the Dlk1‐Dio3 imprinted cluster in testis.     

氰戊菊酯对雄性大鼠生殖内分泌系统的影响

目的 :研究氰戊菊酯 (Fen)对雄性生殖内分泌系统的损害作用及其机制。　方法 :将不同剂量的Fen(0、2 .4、12、6 0mg/kg) ,每日分别对雄性成年SD大鼠连续灌胃 ,染毒 15、30d ,应用RIA法测定大鼠血清中FSH、LH、T和睾丸匀浆中T的水平 ,同步测定睾丸标志酶ACP、γ GT的活性 ,并采用精子头计数法观测每日精子生成量 (Spr)的变化。　结果 :与对照组相比 ,染毒 15d时 ,血清中FSH水平在≤ 12mg/kg剂量组均明显升高 (P <0 .0 1) ,血清中LH含量在 12mg/kg剂量组显著增加 (P <0 .0 1) ,而睾丸匀浆中T在≥ 12mg/kg剂量组中表现为显著下降 (P<0 .0 1) ;染毒至 30d时 ,血清中FSH水平在≥ 12mg/kg剂量范围继续呈现显著增加 (P <0 .0 1) ,睾丸匀浆中T在2 .4mg/kg剂量组则降低 (P <0 .0 5 )。ACP活性在染毒 15d时 2 .4mg/kg剂量组表现为升高 (P <0 .0 5 ) ,继续染毒至 30d时 6 0mg/kg剂量组则显著减低 (P <0 .0 5 ) ;γ GT活性则始终随染毒剂量的增加而降低 (P <0 .0 5 )。Spr与染毒剂量有明显的剂量依赖关系 ,在≥ 12mg/kg剂量范围显著减少 (P <0 .0 1)。 　结论 :Fen对雄性大鼠有明显的生殖毒性 ,可影响其血清及睾丸性激素水平和酶活性 ,这可能与Fen对支持细胞和生精上皮的损害有关     

Embryonic exposure to dimethoate and/or deltamethrin impairs sexual development and programs reproductive success in adult male offspring mice

Pesticides can be toxic to desirable plants and animals, including humans. The aim of this study was to investigate the reproductive effects of low doses of pesticides on male offspring of exposed pregnant mice. Three groups of five female mice were treated daily by oral gavage with dimethoate (5 mg kg(-1) per day), deltamethrin (5 mg kg(-1) per day) and their mixture at 5 mg kg(-1) per day from day 3 to day 21 of pregnancy. Fertility, sexual behaviour and a number of reproductive endpoints, such as organ weights, sperm evaluations and testicular histology, were examined on four adult male offspring of exposed pregnant mice. When compared with control, a dose of deltamethrin 5 mg kg j(-1) causes a decrease in the absolute and relative weight of the testes of exposed mice and it affects their fertility by reducing the density, mobility and vitality of sperm and increasing the number of abnormal forms of these cells (P ≤ 0.01). The same results were obtained in mice exposed to a dose of 5 mg kg j(-1) combination of dimethoate and deltamethrin. This study demonstrated that deltamethrin and combination of dimethoate and deltamethrin caused a decrease in the absolute and relative weight of the testes, which affected the sperm parameters of male offspring of exposed mice to a low dose of these pesticides during pregnancy.     

Abolition of prenatal lipopolysaccharide‐induced reproductive disorders in rat male offspring by fulvestrant

During prenatal and early postnatal periods of development, multiple environmental factors have profound and long‐lasting effects on the immune and reproductive functions. The aim of this study was to investigate the effects of maternal lipopolysaccharide (LPS) exposure (50 mg/kg, i.p.) at day 12 of pregnancy and estradiol antagonist treatment (fulvestrant, 1.5 mg/kg, s.c. in neck) at postnatal days 5–14 (PND5–14) with high estradiol levels on reproductive parameters in adult rat males. Serum steroid concentrations were measured in male offspring at PND80 by ELISA. Body, testis weights and ano‐genital distance (AGD) were recorded at different stages of postnatal development. Testis was also processed to cytohistological studies at PND80. Our results demonstrate that body weight was decreased from PND14 to 30 after prenatal LPS treatment and was increased after fulvestrant treatment. AGD was decreased after prenatal LPS treatment and was increased after fulvestrant injections. Testis weight, testosterone level, seminiferous tubule diameter, and number of Sertoli and spermatid cells were also decreased in rats exposed prenatally to LPS and were restored to the normal control level after fulvestrant treatment. According to results, we can conclude that the development of sexual disorders in males after prenatal immune stress is potentiated by estradiol during the pre‐pubertal period.