In utero combined di-(2-ethylhexyl) phthalate and diethyl phthalate exposure cumulatively impairs rat fetal Leydig cell development
In utero combined di-(2-ethylhexyl) phthalate and diethyl phthalate exposure cumulatively impairs rat fetal Leydig cell development
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子宫内邻苯二甲酸二(2-乙基己基)酯和邻苯二甲酸二乙酯的联合暴露会累积损害大鼠胎儿 Leydig 细胞的发育
DOI：
10.1016/j.tox.2018.01.002
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发表时间：
2018-02-15
期刊：
影响因子：
4.5
通讯作者：
Ge, Ren-Shan
中科院分区：
文献类型：
--
作者：
Hu, Guoxin;Li, Junwei;Ge, Ren-Shan
邻苯二甲酸二酯，包括邻苯二甲酸二（2-乙基己基）酯（DEHP）和邻苯二甲酸二乙酯（DEP），是人类普遍暴露的化学品。人类同时暴露于多种环境化学物质，包括DEHP和DEP。关于每种化学品在同时暴露时如何相互作用的信息很少。本研究探讨了大鼠联合暴露于DEP和DEHP对胎儿Leydig细胞发育的影响。结果表明，妊娠期（GD 12 -20）暴露于DEP + DEHP对胎儿Leydig细胞的发育产生协同和/或剂量累加效应。观察到的胎儿Leydig细胞（聚集和细胞大小）和星星表达的最低不良作用水平（LOAEL）为10 mg/kg，低于单独接触这些化学品时的水平。此外，响应曲线的数学建模支持剂量添加模型优于积分添加模型。总体而言，这些数据表明，当作为混合物给药时，具有相似作用机制的单个邻苯二甲酸酯可对雄性生殖系统发育产生累积、剂量累加和有时协同效应。
Phthalate diesters, including di-(2-ethylhexyl) phthalate (DEHP) and diethyl phthalate (DEP), are chemicals to which humans are ubiquitously exposed. Humans are exposed simultaneously to multiple environmental chemicals, including DEHP and DEP. There is little information available about how each chemical may interact to each other if they were exposed at same time. The present study investigated effects of the combinational exposure of rats to DEP and DEHP on fetal Leydig cell development. The results showed that the gestational (GD12-20) exposure of DEP + DEHP resulted in synergistic and/or dose-additive effects on the development of fetal Leydig cell. The lowest observed adverse-effect levels (LOAEL) for fetal Leydig cell (aggregation and cell size), and StAR expressions were of 10 mg/kg and, lower than when these chemicals were exposed alone. Also, mathematical modeling the response curves supports the dose-addition model over integrated-addition model. Overall, these data demonstrate that individual phthalate with a similar mechanism of action can elicit cumulative, dose additive, and sometimes synergistic, effects on the development of male reproductive system when administered as a mixture.