孕激素醋酸甲地孕酮和雌激素乙炔雌二醇复合暴露对斑马鱼的生殖毒性  

Reproductive toxicity caused by co-exposure of zebrafish to progestin megestrol acetate and estrogen 17α-ethinylestradiol

作　　者：庄太凤[1] 韩建[2] 刘丽玉[3] 华江环[4,5] 

机构地区：[1]首都医科大学附属北京妇产医院,北京100026 [2]山东省科学院生物研究所,济南250014 [3]北京理工大学材料学院,北京100081 [4]湖北中医药大学基础医学院,武汉430065 [5]中国科学院水生生物研究所,淡水生态与生物技术国家重点实验室,武汉430072

出　　处：《环境化学》2017年第7期1440-1450,共11页Environmental Chemistry

基　　金：山东省自然科学基金三院联合基金(ZR2015YL013)资助~~

摘　　要：水生生物往往暴露于多种环境激素(如孕激素、雌激素)的混合物中,然而关于多种环境激素对鱼类的联合作用效应的研究较少.孕激素醋酸甲地孕酮(MTA)和雌激素乙炔雌二醇(EE2)是应用广泛的高活性药物,普遍存在于水环境中,二者均能引起鱼类的生殖毒性效应.本文研究了环境相关浓度的MTA和EE2复合暴露对斑马鱼的生殖毒性效应.将斑马鱼成鱼暴露于MTA(33,100 ng·L^(-1))、EE2(5,15 ng·L^(-1))以及二者的混合物(MTA+EE2:33+5 ng·L^(-1),100+15 ng·L^(-1))21 d,结果显示,EE2(15 ng·L^(-1))单独及与MTA(100 ng·L^(-1))复合暴露显著降低斑马鱼的产卵量;MTA、EE2单独及复合暴露均显著降低雌鱼血浆中雌二醇(E2)、睾酮(T)及雄鱼血浆中11-酮基睾酮(11-KT)的含量;EE2单独及与MTA复合暴露导致斑马鱼卵巢的组织学变化(抑制卵子发生,诱导卵泡闭锁),但对精巢影响较小.此外,复合暴露组中斑马鱼的产卵量、血浆性激素含量、性腺组织学变化与EE2单独暴露组相比均无显著差异.本研究表明,MTA和EE2复合暴露可引起斑马鱼的生殖毒性,其中EE2发挥主要毒性作用.本研究结果对于水环境中多种激素复合暴露的风险评估具有重要意义.Despite potential exposure of aquatic organisms to mixtures of environmental hormones （e.g., progestins, estrogens）, very little is known about their binary activity in fish. Synthetic progestin megestrol acetate （MTA） and estrogen 17α-ethinylestradiol （EE2） are widely used pharmaceutical agents with high bioactivity, and have been frequently detected in the aquatic environment. They both can cause reproductive toxicity in fish. In the present study, we investigated the combined reproductive effects of MTA and EE2 at environmentally relevant concentrations on zebrafish. Adult zebrafish were exposed to MTA （33 or 100 ng·L-1）, EE2 （5 or 15 ng·L-1） or a mixture of both （MTA ＋ EE2： 33 ＋ 5 ng·L-1, 100 ＋ 15 ng·L-1） for 21 d. Results demonstrated that the egg production was significantly reduced by exposure to 15 ng·L-1 EE2 alone or combined exposure to 100 ng·L-1 MTA and 15 ng·L-1 EE2. Plasma concentrations of estradiol （E2） and testosterone （T） in females and 11-ketotestosterone （11-KT） in males were all significantly decreased after exposure to EE2 or MTA or the mixtures of both chemicals. Besides, exposure to EE2 or the mixtures led to histological alterations in the ovaries （inhibition of oogenesis, induction of atresia）, but little effects were found on the testes. In addition, no significant difference was found in egg production, plasma concentrations of sex hormones and gonadal histological alterations in co-exposure groups when compared with those in EE2 single exposure groups. The present study suggests that co-exposure to environmentally relevant concentrations of MTA and EE2 could result in reproductive toxicity in zebrafish, and EE2 plays a predominant role in causing the dysfunctions. The present study has important implications for environmental risk assessment of combined exposure to environmental hormones present in aquatic environment.

关 键 词：醋酸甲地孕酮 乙炔雌二醇 复合暴露 生殖毒性 斑马鱼 

分 类 号：X171.5[环境科学与工程—环境科学]