UMR CNRS 8638 Chimie Toxicologie Analytique et Cellulaire, Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l'Observatoire, 75006 Paris, France.
UMR-S 1139 Physiopathologie et Pharmaco-Toxicologie Placentaire Humaine, Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l'Observatoire, 75006 Paris, France.
Biochimie. 2018 Jun;149:1-8. doi: 10.1016/j.biochi.2018.03.002. Epub 2018 Mar 19.
During pregnancy, exposure to environmental contaminants can lead to adverse effects on fetal growth and development, especially by targeting the placenta. Di(2-ethylhexyl)phthalate (DEHP), the most abundant chemical used in plastic materials, is known to induce toxicity on animals reproductive system and is suspected to give rise to similar effect in humans. Toxicity of DEHP is due to its main metabolite, MEHP, which is also known to disturb lipid synthesis in several organs. Moreover, mono-(2-ethylhexyl)phtalate (MEHP) is a high affinity ligand of the peroxisome proliferator-activated receptor PPARγ which is essential for placental development and lipid metabolism. In order to investigate possible lipid disruptions induced by MEHP, in the JEG-3 human trophoblast cell line, a differential lipidomic analysis was carried out by UPLC-MS on both exposed and control cells. Our results showed that MEHP induced an important change of JEG-3 cells lipidome, especially in glycerolipids and glycerophospholipids, with a marked accumulation of triacylglycerols. For the first time, our results highlighted adverse effects of MEHP on human placental cells lipidome and thus, its potential effect on placental physiology.
在怀孕期间，暴露于环境污染物会对胎儿的生长和发育产生不良影响，特别是通过作用于胎盘。邻苯二甲酸二（2-乙基己基）酯（DEHP）是塑料材料中使用最广泛的化学物质，已知其对动物生殖系统具有毒性，并怀疑对人类具有类似的影响。DEHP 的毒性是由于其主要代谢物 MEHP 引起的，MEHP 还已知会扰乱几个器官的脂质合成。此外，单（2-乙基己基）邻苯二甲酸酯（MEHP）是过氧化物酶体增殖物激活受体 PPARγ 的高亲和力配体，PPARγ 对于胎盘发育和脂质代谢至关重要。为了研究 MEHP 可能引起的脂质紊乱，在 JEG-3 人滋养层细胞系中，通过 UPLC-MS 对暴露和对照细胞进行了差异脂质组学分析。我们的结果表明，MEHP 诱导 JEG-3 细胞脂质组发生重要变化，特别是甘油酯和甘油磷脂，三酰基甘油明显积累。这是首次强调 MEHP 对人胎盘细胞脂质组的不良影响，以及其对胎盘生理学的潜在影响。
