Gyeongnam Department of Environmental Toxicology and Chemistry, Korea Institute of Toxicology (KIT), Gyeonsangnam-do, 52834, Republic of Korea.
Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe, Saarbrücken, 661c23, Germany.
Environ Pollut. 2020 Oct;265(Pt B):114362. doi: 10.1016/j.envpol.2020.114362. Epub 2020 Mar 11.
This study aimed to investigate the effect of mono-(2-ethylhexyl) phthalate (MEHP), one of the major phthalate metabolites that are widespread in aquatic environments, on reproductive dysfunction, particularly on endocrine activity in adult male and female zebrafish. For 21 days, the zebrafish were exposed to test concentrations of MEHP (0, 2, 10, and 50 μg/mL) that were determined based on the effective concentrations (ECx) for zebrafish embryos. Exposure to 50 μg/mL MEHP in female zebrafish significantly decreased the number of ovulated eggs as well as the hepatic VTG mRNA abundance when those of the control group. Meanwhile, in female zebrafish, the biosynthetic concentrations of 17β-estradiol (E2) and the metabolic ratio of androgen to estrogen were remarkably increased in all MEHP exposed group compared with those in the control group, along with the elevated levels of cortisol. However, no significant difference was observed between these parameters in male zebrafishes. Therefore, exposure to MEHP causes reproductive dysfunction in female zebrafishes and this phenomenon can be attributed to the alteration in endocrine activities. Moreover, the reproductive dysfunction in MEHP-exposed female zebrafishes may be closely associated with stress responses, such as elevated cortisol levels. To further understand the effect of MEHP on the reproductive activities of fish, follow-up studies are required to determine the interactions between endocrine activities and stress responses. Overall, this study provides a response biomarker for assessing reproductive toxicity of endocrine disruptors that can serve as a methodological approach for an alternative to chronic toxicity testing.
本研究旨在探讨邻苯二甲酸单(2-乙基己基)酯(MEHP)作为一种广泛存在于水生环境中的主要邻苯二甲酸代谢物之一对生殖功能障碍的影响,特别是对成年雌雄斑马鱼的内分泌活动的影响。在 21 天的时间里,斑马鱼暴露于根据对斑马鱼胚胎的有效浓度(ECx)确定的 MEHP 测试浓度(0、2、10 和 50μg/mL)下。与对照组相比,暴露于 50μg/mL MEHP 的雌性斑马鱼的排卵卵数和肝脏 VTG mRNA 丰度显著降低。同时,在雌性斑马鱼中,与对照组相比,所有 MEHP 暴露组的 17β-雌二醇(E2)的生物合成浓度和雄激素与雌激素的代谢比值均显著增加,同时皮质醇水平升高。然而,在雄性斑马鱼中,这些参数之间没有观察到显著差异。因此,MEHP 的暴露导致雌性斑马鱼生殖功能障碍,这种现象可归因于内分泌活动的改变。此外,MEHP 暴露的雌性斑马鱼的生殖功能障碍可能与应激反应密切相关,例如皮质醇水平升高。为了进一步了解 MEHP 对鱼类生殖活动的影响,需要进行后续研究以确定内分泌活动和应激反应之间的相互作用。总的来说,本研究为评估内分泌干扰物的生殖毒性提供了一个反应生物标志物,可以作为替代慢性毒性测试的方法。