邻苯二甲酸二(2-乙基己)酯和邻苯二甲酸单乙基己基酯对幼年期及青年期海洋青鳉(Oryzias melastigma)的内分泌干扰效应

Endocrine-disrupting effects of DEHP and MEHP on the fry and juvenile stage medaka( Oryzias melastigma)

本研究从邻苯二甲酸二(2-乙基己)酯(DEHP)和邻苯二甲酸单乙基己酯(MEHP)对幼鱼期及青年期海洋青鳉(Oryzias melastigma)的生殖发育毒性效应出发,从雌激素受体(ER)、过氧化物增殖激活受体(PPAR)及芳香烃受体(AhR)通路探讨DEHP和MEHP致毒机制.本实验将孵化后1周的幼鱼分别暴露于溶剂对照、低浓度DEHP(0.1 mg·L-1)、高浓度DEHP(0.5 mg·L-1)、低浓度MEHP(0.1 mg·L-1)和高浓度MEHP(0.5 mg·L-1)23 d、53 d,组织病理学结果显示,DEHP和MEHP导致雌性青鳉肝损伤,表现为肝糖原降低,肝细胞质水肿变性;DEHP和MEHP促进了性成熟,表现为促进雌性青鳉卵巢中卵细胞的发育.荧光定量PCR结果显示,DEHP和MEHP显著影响了ER、PPAR及AhR通路,并且对青年期的影响强于幼鱼期,DEHP对ER、PPAR及AhR通路的影响较MEHP强.所以DEHP及MEHP可能通过ER、PPAR和AhR通路影响了肝脏发育,造成了肝损伤,促进雌性青鳉卵巢发育,对ER、PPAR和AhR通路影响显示出发育阶段特异性.

Our study investigated the reproductive and developmental effects of DEHP and MEHP on the fry and juvenile stage medaka （ Oryzias melastigma）. To analyze the mechanisms of toxicity of DEHP and MEHP, we examined the transcriptional responses of estrogen receptor （ ER）, aryl hydrocarbon receptor （AhR） and peroxisome proliferator-activated receptor （PPAR） pathway related genes on medaka. The medaka larvae （One week post hatching） were exposed to DEHP （0.1 mg·L^-1 or0.5 mg·L^-1） and MEHP （0.1 mg·L^-1 or 0.5 mg·L^-1） for 23 days and 53 days, respectively. Histological results showed DEHP and MEHP caused liver damage. Decrease in glycogen content and cytoplasmic hydropic degenerations were observed. DEHP and MEHP promoted sexual maturity of female medaka by promoting the development of ovaries. RT-PCR results of fry and juvenile stage medaka showed DEHP and MEHP exhibited transcriptional responses on the examined genes related to ER, PPAR and AhR pathways. The effects on juvenile stage medaka were more severe than that on fry stage medaka, and the effects of DEHP on these pathways were more obvious than that of MEHP. In conclusion, DEHP and MEHP caused liver damage and promoted the development of oocytes, which may work through activation of ER, PPAR and AhR pathways; and the effects of DEHP and MEHP on these pathways showed stage specific effects.