Université de Paris, CNRS CiTCoM, 75006 Paris, France.
Laboratoires Léa Nature, Recherche & Développement, 17180 Périgny, France.
Cells. 2022 Jan 31;11(3):495. doi: 10.3390/cells11030495.
In pregnant women, the lungs, skin and placenta are exposed daily to endocrine-disrupting chemicals (EDCs). EDCs induce multiple adverse effects, not only on endocrine organs, but also on non-endocrine organs, with the P2X7 cell death receptor being potentially the common key element. Our objective was first to investigate mechanisms of EDCs toxicity in both endocrine and non-endocrine cells through P2X7 receptor activation, and second, to compare the level of activation in lung, skin and placental cells. In addition, apoptosis in placental cells was studied because the placenta is the most exposed organ to EDCs and has essential endocrine functions. A total of nine EDCs were evaluated on three human cell models. We observed that the P2X7 receptor was not activated by EDCs in lung non-endocrine cells but was activated in skin and placenta cells, with the highest activation in placenta cells. P2X7 receptor activation and apoptosis are pathways shared by all tested EDCs in endocrine placental cells. P2X7 receptor activation along with apoptosis induction could be key elements in understanding endocrine placental and skin disorders induced by EDCs.
在孕妇中，肺部、皮肤和胎盘每天都会接触到内分泌干扰化学物质（EDCs）。EDCs 不仅会对内分泌器官，还会对非内分泌器官产生多种不良影响，P2X7 细胞死亡受体可能是潜在的共同关键因素。我们的目标首先是通过 P2X7 受体的激活来研究 EDCs 在内分泌和非内分泌细胞中的毒性机制，其次是比较肺、皮肤和胎盘细胞中的激活水平。此外，我们还研究了胎盘细胞的细胞凋亡，因为胎盘是最容易受到 EDC 暴露的器官，并且具有重要的内分泌功能。总共评估了 9 种 EDC 在 3 个人类细胞模型上的作用。我们观察到，P2X7 受体在肺非内分泌细胞中不受 EDC 激活，但在皮肤和胎盘细胞中被激活，其中胎盘细胞的激活程度最高。P2X7 受体的激活和细胞凋亡是所有测试的 EDC 在内分泌胎盘细胞中共同的途径。P2X7 受体的激活和诱导细胞凋亡可能是理解 EDC 引起的内分泌胎盘和皮肤紊乱的关键因素。
