敌敌畏、乐果和马拉硫磷混合染毒对雄性小鼠生殖功能的影响
Synergistic effect of dichlorovos,dimethoate and malathion mixture on reproduction toxicity in male mice
摘要目的 研究敌敌畏、乐果和马拉硫磷混合染毒后对雄性小鼠生殖功能影响的特点和可能机制。方法 将105只雄性ICR小鼠按体重分层随机分成7组,每组15只,即对照组(0 mg/kg),敌敌畏、乐果和马拉硫磷混合低( 10.8 mg/kg)、中(21.5mg/kg)、高剂量组(43.0 mg/kg),以及敌敌畏组(5.1 mg/kg)、乐果组(12.6 mg/kg)和马拉硫磷组(25.3 mg/kg),经口连续灌胃染毒35 d,每天1次。染毒第36天后处死动物。测量小鼠体重、精子活力,观察精子数量及精子畸形率,检测血清中性激素[包括睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)等]的水平,并观察睾丸及附睾的病理及电镜下改变。结果 染毒后第14天,混合高剂量组小鼠体重[(22.40±3.07)g]低于对照组[(26.73±2.82)g](P<0.05);染毒后第28天,混合中剂量组小鼠体重[(30.00±4.93)g]亦低于对照组[(33.13±3.29)g](P <0.05)。混合中、高剂量组精子数[分别为(321.17±18.19)×106/g附睾重、(225.00±19.67)×106/g附睾重]和精子活力[分别为(64.67±9.91)%、(57.83±9.66)%]均低于对照组[分别为( 373.33±14.65)× 106/g附睾重、(75.17±7.68)%](P值均<0.05);精子畸形率[分别为(43.33 ±8.66)‰、(55.00±13.80)‰]高于对照组[(32.67±8.17)‰](P值均<0.05);与对照组相比[FSH、E2、LH、T分别为(1.41±0.20)、(17.32±2.72)、(8.75±1.32)、(3.45±0.80)nmol/L],混合中、高剂量组小鼠血清中FSH[分别为(3.14±0.62)、(3.85±0.37) nmol/L]、E2[分别为(36.81±6.68)、(43.76±9.82)nmol/L]水平升高(P值均<0.01),LH[分别为(5.21 ±1.23)、(4.27±1.09) nmol/L]、T[分别为(1.37±0.38)、(0.73±0.18)nmol/L]水平降低(P值均<0.01)。混合高剂量组小鼠睾丸成熟精子数减少,并可见结构异常的精子头、精子尾。结论 敌敌畏、乐果和马拉硫磷混合联合染毒可直接损害小鼠睾丸及附睾的结构和功能,而导致生殖细胞生成过程异常;并导致下丘脑-垂体-性腺轴性激素的分泌紊乱。
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abstractsObjective To evaluate the reproduction toxicity of the mixture composed of dichlorovos,dimethoate and malathion synergistic effect on male mice, and further explore its possible mechanisms. Methods The 105 male mice were divided into 7 groups,including control (0 mg/kg) ,mix low (10.8 mg/kg),mix medium (21.5 mg/kg),mix high doee (43.0 mg/kg) ,dichlorovos (5.1 mg/kg),dimethoate (12.6 mg/kg) and malathion (25.3 mg/kg) group. The oral gavage for successive 35 days,and the mice were sacrificed on the 36th day. The body weight,and the quantity,activity and morphology of sperms were examined. The levels of sexual hormone were measured, including testosterone (T), follicle stimulating hormone ( FSH ), luteinizing hormone ( LH ) and estradiol ( E2 ). Pathological changes of testicle and epididymis were observed by morphology, pathology and electron microscope. ResultsAfter 14 days exposure,the body weights of the mice were lower in the mix-high dose group ( ( 22.40 ± 3.07 ) g ) than those in control group ( (26.73 ± 2.82 ) g ) ( P < 0.05 ). After 28 days exposure, the body weights of the mice were also lower in the mix-medium dose group ( ( 30.00 ± 4.93 ) g) than those in control group ((33.13 ±3.29)g) (P <0.05). The sperm counts and sperm motility decreased significantly as the toxic concentration arised. Comparing to control group ( ( 373.33 ± 14.65 ) × 106/g weight of epididymis and (75.17 ±7.68)% ) ,the spermatozoa count and sperm motility had decreased in mix-medium and mix-high dose groups ((321.17 ± 18.19) × 106/g weight of epididymis, (225.00 ± 19.67) × 106/g weight of epididymis, and ( 64.67 ± 9.91 ) %, ( 57.83 ± 9.66 ) % ), and the sperm abnormality rates were higher in mix-medium and mix-high groups ((43.33 ± 8.66)‰ and (55.00 ± 13.80)‰) comparing to those in control group ( (32.67 ±8.17) ‰). Compared to those in control group ( FSH( 1.41 ±0.20) ,E2( 17.32 ±2.72), LH ( 8.75 ± 1.32 ) and T ( 3.45 ± 0.80 ) nmol/L ) , the serum level of FSH ( 3.14 ± 0.62 ) and ( 3.85 ± 0.37 ) nmol/L, E2 ( 36.81 ± 6.68) and (43.76 ± 9.82) nmol/L in mix-medium and mix-high dose group increased ( P < 0.01 ), while the level of LH ( 5.21 ± 1.23 ) and ( 4.27 ± 1.09 ) nmol/L and T (1.37±0.38) and (0.73 ± 0.18) nmol/L decreased (P< 0.01).The morphological and ultramicrostructure results of testicle and epididymis indicated that the mature sperm numbers were decreased,and the cacoplastic sperm head and the tail of spermatozoon were observed in mix-high dose groups. Conclusion The dichlorovos, dimethoate and malathion mixture had synergistic reproductive toxicity to the testicle and epididymis structure and function, and thus leading to the process of generation cell cytopoiesis abnormalities, simultaneously the hypothalamus-pituitary-gonad axis were also affected and thus resulted in parasecretion.
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