Endocrine-disrupting chemicals (EDCs) have multiple adverse effects, not only on endocrine organs but also on non-endocrine organs. This is possibly due to a common feature: a receptor called P2X7 on cell surfaces. The receptor is actually a non-specific cation channel that responds, among other things, to extracellular ATP from dying cells as a result of inflammation. P2X7 activation can trigger a variety of cellular responses not normally associated with ion channel function, such as changes in plasma membrane composition and morphology, ectodomain detachment, activation of lipases, kinases, and transcription factors, as well as cytokine release and apoptosis.^{(1, 2)} Therefore, it is also called an apoptosis receptor.

The aim of the present study was to investigate the toxic effect of different EDCs in different cell lines by the common cellular mechanism and to compare the different extent in the cells. For their studies, the team used human lung epithelial cells, keratinocytes as well as villous trophoblastic placental cells to compare the extent of P2X7 receptor activation after incubation with different EDCs. The placenta is a crucial organ during pregnancy and is most exposed to EDCs. Activation of the P2X7 receptor can lead to programmed cell death, resulting in pregnancy disorders such as pre-eclampsia or premature birth.

All three cell lines form functional P2X7 receptors and reacted in different ways to the hormone-active chemicals. The researchers were able to show that the P2X7 receptors were not activated in non-hormone-responsive cells of the lungs, but were active in skin and placental cells. The receptors were most strongly activated in placental cells.

The researchers concluded that P2X7 receptor activation, along with apoptosis induction, may be key elements in understanding endocrine placental and skin diseases triggered by hormone-responsive chemicals.

Source and further information:
Fouyet S, Olivier E, Leproux P, Dutot M, Rat P. Pregnant Women and Endocrine Disruptors: Role of P2X7 Receptor and Mitochondrial Alterations in Placental Cell Disorders. Cells. 2022 Jan 31;11(3):495. doi: 10.3390/cells11030495. PMID: 35159304; PMCID: PMC8834275.

Additional information:
⁽¹⁾ Kopp R, Krautloher A, Ramírez-Fernández A, Nicke A. P2X7 Interactions and Signaling - Making Head or Tail of It. Front Mol Neurosci. 2019 Aug 7;12:183. doi: 10.3389/fnmol.2019.00183. PMID: 31440138; PMCID: PMC6693442.
⁽²⁾ Shokoples BG, Paradis P, Schiffrin EL. P2X7 Receptors: An Untapped Target for the Management of Cardiovascular Disease. Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):186-199. doi: 10.1161/ATVBAHA.120.315116. Epub 2020 Oct 1. PMID: 32998520; PMCID: PMC7752223.