College of Ecological Technology and Engineering, Shanghai Institute of Technology, Shanghai 201418, PR China.
College of Ecological Technology and Engineering, Shanghai Institute of Technology, Shanghai 201418, PR China; Jiaxing Tongji Institute for Environment, Jiaxing, Zhejiang 314051, PR China.
Sci Total Environ. 2023 Nov 10;898:165268. doi: 10.1016/j.scitotenv.2023.165268. Epub 2023 Jul 3.
Di-n-octyl phthalate (DOP) is one important phthalate analog whose toxicities need comprehensive investigation to fully demonstrate phthalates health risks. In the present study, apical effects of DOP on behavior, lifespan and reproduction and the underlying mechanisms were explored in Caenorhabditis elegans for four consecutive generations (F1 to F4) and the trans-generational effects were also measured in the great-grand-children (T4 and T4') of F1 and F4. Multi-generational results showed that DOP caused both stimulation and inhibition on head swing, body bending, reverse, Omega steering, pharyngeal pump and satiety quiescence. The stimulation and inhibition altered over concentrations and across generations, and the alteration was the greatest in reverse locomotion which showed both concentration-dependent hormesis and trans-hormesis. DOP stimulated lifespan and inhibited reproduction, showing trade-off relationships. Significant trans-generational residual effects were found in T4 and T4' where the exposure was completed eliminated. Moreover, both similar and different effects were found in comparisons between F1 and F4, between F1 and T4, between F4 and T4' and also between T4 and T4'. Further analysis showed close connections between effects of DOP on neurotransmitters (including dopamine, acetylcholine, γ-aminobutyric acid and serotonin) and enzymes in lipid metabolism (including lipase, acetyl CoA carboxylase, fatty acid synthetase, carnitine palmitoyl-transferase, glycerol phosphate acyltransferase and acetyl CoA synthetase). Moreover, the close connections were also found between biochemical and apical effects. Notably, the connections were different in multi- and trans-generational effects, which urged further studies to reveal the response strategies underlying the exposure scenarios.
邻苯二甲酸二辛酯（DOP）是一种重要的邻苯二甲酸酯类似物，其毒性需要全面研究，以充分证明邻苯二甲酸酯对健康的风险。在本研究中，连续四代（F1 到 F4）探索了 DOP 对秀丽隐杆线虫行为、寿命和繁殖的顶端效应及其潜在机制，并测量了 F1 和 F4 的曾孙（T4 和 T4'）的跨代效应。多代结果表明，DOP 对头部摆动、身体弯曲、反转、Ω转向、咽泵和饱足静止都有刺激和抑制作用。刺激和抑制作用随浓度和代际而变化，反转运动的变化最大，表现出浓度依赖性和跨激素作用。DOP 刺激寿命并抑制繁殖，表现出权衡关系。在 T4 和 T4'中发现了显著的跨代残留效应，而暴露已经完全消除。此外，在 F1 和 F4、F1 和 T4、F4 和 T4'以及 T4 和 T4'之间的比较中，都发现了类似和不同的效应。进一步的分析表明，DOP 对神经递质（包括多巴胺、乙酰胆碱、γ-氨基丁酸和血清素）和脂质代谢酶（包括脂肪酶、乙酰辅酶 A 羧化酶、脂肪酸合成酶、肉碱棕榈酰转移酶、甘油磷酸酰基转移酶和乙酰辅酶 A 合成酶）的影响之间存在密切联系。此外，生化和顶端效应之间也存在密切联系。值得注意的是，在多代和跨代效应中，这些联系是不同的，这促使进一步的研究揭示暴露场景下的反应策略。
