围生期低剂量邻苯二甲酸二-(2-乙基)己酯对子代雄性大鼠发育及性激素水平的影响
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摘要
目的探讨围生期低剂量邻苯二甲酸二-(2-乙基)己酯(DEHP)暴露对子代成年雄性小鼠发育及血清睾丸中雌激素(E2)和睾酮(T)水平的影响。方法将20只妊娠6 d的昆明小鼠随机分为对照组、1、10、100μg/kg DEHP染毒组,每组各5只,分别灌胃玉米油、1、10、100μg/kg DEHP溶液,1次/d,染毒至哺乳期出生后21 d(PDN21)结束。仔鼠断乳后每周称量1次至PDN84时,每组随机选取10只雄性仔鼠,摘取脾脏、肝脏、肾脏、胸腺并测定其重量,并计算脏器系数;同时测定各组小鼠血清和睾丸匀浆组织中E2和T水平。结果 100μg/kg DEHP染毒组子代成年雄性小鼠在PDN0、49、56、63、70、77时的体重均显著低于对照组,差异有统计学意义(P<0.05);各组子代成年雄性小鼠PDN84时的体重比较,差异无统计学意义(P>0.05)。肝脏和胸腺重量及其脏器系数方面,三组子代成年雄性小鼠与对照组比较,差异无统计学意义(P>0.05);100μg/kg DEHP染毒组子代成年雄性小鼠的脾脏重量及其脏器系数显著高于对照组,肾脏重量及脏器系数明显低于对照组,差异有统计学意义(P<0.05)。各DEHP染毒组子代成年雄性小鼠血清中的E_2水平随着染毒剂量的增加而减少,而血清中的T水平呈上升趋势。100μg/kg DEHP染毒组子代成年雄性小鼠睾丸组织匀浆液中的E_2水平显著低于对照组,差异有统计学意义(P<0.05)。其他组子代成年雄性小鼠的E_2水平与对照组比较,差异无统计学意义(P>0.05);各DEHP染毒组子代成年雄性小鼠睾丸组匀浆中的T水平与对照组比较,差异无统计学意义(P>0.05)。结论围生期低剂量DEHP暴露对子代成年雄性小鼠的发育和睾丸组织中的E2水平具有持续的毒性作用。
Objective To investigate the effect of perinatal exposure to low-dose Di-(2-ethyl)hexyl phthalate(DEHP)on the development and the levels of estrogen(E2) and testosterone(T) in serum testis of offspring adult male mice.Methods Altogether 20 Kunming mice with 6 days of pregnancy were randomly divided into control group, 1, 10 and100 μg/kg DEHP infected groups, with 5 mice in each group, and corn oil, 1, 10, 100 μg/kg DEHP solution were given respectively once a day to the end of 21 days after birth to lactation(PDN21). Ten male mice were randomly selected and were weighed once a week to PDN84 after weaning from each group. The spleen, liver, kidney and thymus were extracted and weighed, and the organ coefficient was calculated. The levels of E2 and T in serum and testicular homogenate tissues were detected. Results The body weight of adult male mice at PDN0, 49, 56, 63, 70 and 77 in the100 μg/kg DEHP group was significantly lower than that in the control group, and the difference was statistically significant(P <0.05). There was no significant difference in body weight between adult male mice at PDN84(P >0.05).There were no significant differences in weight and organ coefficient of liver and thymus between the three groups of adult male mice and the control group(P>0.05). The spleen weight and organ coefficient of the adult male mice in the100 μg/kg DEHP group were significantly higher than those in the control group, the kidney weight and organ coefficient were significantly lower than those in the control group, and the differences were statistically significant(P<0.05). The level of E_2 in the serum of adult male mice of each DEHP group decreased with the increasement of the DEHP dose, while the T level in serum increased. The level of E_2 in the testis homogenate of adult male mice in the 100 μg/kg DEHP group was significantly lower than that in the control group, and the difference was statistically significant(P<0.05). The E_2 levels of adult male mice in other DEHP groups were not significantly different from those in the control group(P>0.05). There was no significant difference in the T level between the testes of adult male mice in the DEHP groups and the control group(P>0.05). Conclusion Low dose DEHP exposure during perinatal period has a continuous toxic effect on the development of adult male offspring and the level of E_2 in testicular tissue.
Objective To investigate the effect of perinatal exposure to low-dose Di-(2-ethyl)hexyl phthalate(DEHP)on the development and the levels of estrogen(E2) and testosterone(T) in serum testis of offspring adult male mice.Methods Altogether 20 Kunming mice with 6 days of pregnancy were randomly divided into control group, 1, 10 and100 μg/kg DEHP infected groups, with 5 mice in each group, and corn oil, 1, 10, 100 μg/kg DEHP solution were given respectively once a day to the end of 21 days after birth to lactation(PDN21). Ten male mice were randomly selected and were weighed once a week to PDN84 after weaning from each group. The spleen, liver, kidney and thymus were extracted and weighed, and the organ coefficient was calculated. The levels of E2 and T in serum and testicular homogenate tissues were detected. Results The body weight of adult male mice at PDN0, 49, 56, 63, 70 and 77 in the100 μg/kg DEHP group was significantly lower than that in the control group, and the difference was statistically significant(P <0.05). There was no significant difference in body weight between adult male mice at PDN84(P >0.05).There were no significant differences in weight and organ coefficient of liver and thymus between the three groups of adult male mice and the control group(P>0.05). The spleen weight and organ coefficient of the adult male mice in the100 μg/kg DEHP group were significantly higher than those in the control group, the kidney weight and organ coefficient were significantly lower than those in the control group, and the differences were statistically significant(P<0.05). The level of E_2 in the serum of adult male mice of each DEHP group decreased with the increasement of the DEHP dose, while the T level in serum increased. The level of E_2 in the testis homogenate of adult male mice in the 100 μg/kg DEHP group was significantly lower than that in the control group, and the difference was statistically significant(P<0.05). The E_2 levels of adult male mice in other DEHP groups were not significantly different from those in the control group(P>0.05). There was no significant difference in the T level between the testes of adult male mice in the DEHP groups and the control group(P>0.05). Conclusion Low dose DEHP exposure during perinatal period has a continuous toxic effect on the development of adult male offspring and the level of E_2 in testicular tissue.
引文
[1]付国庆,石玉琴,朱丽姗,等.邻苯二甲酸二乙基己酯对小鼠初级精母细胞氧化应激及凋亡的影响[J].环境与健康杂志,2015,5(4):312-316.
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[10]董晋,董新文,赵跃,等.长期暴露的邻苯二甲酸二(2-乙基己基)酯在雌性大鼠体内的代谢及对肝脏的影响[J].癌变·畸变·突变,2017,29(3):211-215.
[11]刘艳华,刘秋芳,潘亮,等.邻苯二甲酸二(2-乙基)己酯(DEHP)胚胎期暴露对子代大鼠神经行为发育的影响[J].毒理学杂志,2011,25(6):414-417.
[12]黄晨.Chemerin及其受体CMKLR1在实验性小鼠妊娠期糖尿病中作用机制的研究[D].北京:中国科学院大学,2018.
[13]王宇,李登辉,于海洋,等.邻苯二甲酸二乙基己酯与双酚A混合染毒对大鼠睾丸损伤及与氧化应激关系研究[J].毒理学杂志,2018,32(1):29-35.
[14]郑海红,陈翔义,陈玲,等.DEHP对新生雄性仔鼠毒性作用的实验研究[J].医学研究杂志,2012,41(1):28-33.
[15]张伟,高玉杰,张鸿毅,等.邻苯二甲酸二(2-乙基)己酯对两代雄性大鼠生殖毒性的研究[J].西南国防医药,2008,18(4):487-491.
[16]胡帅尔,张紫红,王风岩,等.邻苯二甲酸二(2-乙基)对大鼠的亚慢性毒性研究[J].环境与健康杂志,2015,7(32):632-634.
[17]辛全兵,主桂莲,王成恩,等.围产期低剂量氯化三丁基锡暴露对子代成年雄性小鼠发育及性激素水平的影响[J].环境与健康杂志,2012,29(9):783-786.
[18]衷筱琴,蔡红平,万红萍,等.邻苯二甲酸二(2-乙基己基)酯对大鼠不同脏器的损伤[J].环境与健康杂志,2009,26(3):212-214.
[2]蒋磊,徐维平,芮贝贝,等.邻苯二甲酸二乙基己酯体内代谢和毒性机制研究进展[J].中国药业,2015,24(5):1-4.
[3]沈炼桔,唐向亮,龙春兰,等.邻苯二甲酸二-(22-乙基己基)酯对血睾屏障完整性的损伤及机制[J].南方医科大学学报,2017,37(9):1178-1182.
[4]Wang YX,You L,Zeng Q,et al.Phthalate exposure and humansemen quality:results from an infertility clinic in China[J].Environ Res,2015,142(5):1-9.
[5]Abd-Ellah MF,Aly HA,Mokhlis HA,et al.Quercetin attenuates di-(2-ethylhexyl)phthalate-induced testicular toxicity in adult rats[J].Hum Exp Toxicol,2016,35(3):232-243.
[6]刘殊,戴红.邻苯二甲酸二(2-乙基)己酯致雄性生殖毒性及其机制的研究进展[J].中外医疗,2015,34(24):193.
[7]成神洲,常薇,郭星,等.邻苯二甲酸二(2-乙基己基)酯对青春前期雄性大鼠的生殖毒性[J].环境与健康杂志,2016,33(9):781-785.
[8]秦逍云,谭琴,徐新云,等.邻苯二甲酸二(2-乙基己)酯对雄性大鼠激素相关基因表达水平的影响[J].癌变·畸变·突变,2015.26(5):365-368.
[9]刘瑾,卢晓丽,吴玲玉,等.邻苯二甲酸二乙基己酯对未成年雌性小鼠血清脂质过氧化及肝功能指标的影响[J].环境与健康杂志,2014,31(6):537-538.
[10]董晋,董新文,赵跃,等.长期暴露的邻苯二甲酸二(2-乙基己基)酯在雌性大鼠体内的代谢及对肝脏的影响[J].癌变·畸变·突变,2017,29(3):211-215.
[11]刘艳华,刘秋芳,潘亮,等.邻苯二甲酸二(2-乙基)己酯(DEHP)胚胎期暴露对子代大鼠神经行为发育的影响[J].毒理学杂志,2011,25(6):414-417.
[12]黄晨.Chemerin及其受体CMKLR1在实验性小鼠妊娠期糖尿病中作用机制的研究[D].北京:中国科学院大学,2018.
[13]王宇,李登辉,于海洋,等.邻苯二甲酸二乙基己酯与双酚A混合染毒对大鼠睾丸损伤及与氧化应激关系研究[J].毒理学杂志,2018,32(1):29-35.
[14]郑海红,陈翔义,陈玲,等.DEHP对新生雄性仔鼠毒性作用的实验研究[J].医学研究杂志,2012,41(1):28-33.
[15]张伟,高玉杰,张鸿毅,等.邻苯二甲酸二(2-乙基)己酯对两代雄性大鼠生殖毒性的研究[J].西南国防医药,2008,18(4):487-491.
[16]胡帅尔,张紫红,王风岩,等.邻苯二甲酸二(2-乙基)对大鼠的亚慢性毒性研究[J].环境与健康杂志,2015,7(32):632-634.
[17]辛全兵,主桂莲,王成恩,等.围产期低剂量氯化三丁基锡暴露对子代成年雄性小鼠发育及性激素水平的影响[J].环境与健康杂志,2012,29(9):783-786.
[18]衷筱琴,蔡红平,万红萍,等.邻苯二甲酸二(2-乙基己基)酯对大鼠不同脏器的损伤[J].环境与健康杂志,2009,26(3):212-214.