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Our previous study confirmed that TPhP could accumulate in the placenta and interference with placental lipid metabolism and steroid hormone synthesis, as well as induce endoplasmic reticulum (ER) stress through PPAR\u03b3 in human placental trophoblast JEG\u20103 cells. However, the molecular mechanism underlying this disruption remains unknown. Our study aimed to identify the role of the PPAR\u03b3\/CD36 pathway in TPhP\u2010induced steroid hormone disruption. We found that TPhP increased lipid accumulation, total cholesterol, low\u2010 and high\u2010density protein cholesterol, progesterone, estradiol, glucocorticoid, and aldosterone levels, and genes related to steroid hormones synthesis, including <jats:italic>3\u03b2HSD1<\/jats:italic>, <jats:italic>17\u03b2HSD1<\/jats:italic>, <jats:italic>CYP11A<\/jats:italic>, <jats:italic>CYP19<\/jats:italic>, and <jats:italic>CYP21<\/jats:italic>. These effects were largely blocked by co\u2010exposure with either a PPAR\u03b3 antagonist GW9662 or knockdown of CD36 using siRNA (siCD36). Furthermore, an ER stress inhibitor 4\u2010PBA attenuated the effect of TPhP on progesterone and glucocorticoid levels, and siCD36 reduced ER stress\u2010related protein levels induced by TPhP, including BiP, PERK, and CHOP. These findings suggest that ER stress may also play a role in the disruption of steroid hormone synthesis by TPhP. As our study has shed light on the PPAR\u03b3\/CD36 pathway's involvement in the disturbance of steroid hormone biosynthesis by TPhP in the JEG\u20103 cells, further investigations of the potential impacts on the placental function and following birth outcome are warranted.<\/jats:p>","DOI":"10.1002\/tox.24186","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T11:03:56Z","timestamp":1709809436000},"page":"3400-3409","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Triphenyl phosphate interferes with the synthesis of steroid hormones through the <scp>PPAR\u03b3<\/scp>\/<scp>CD36<\/scp> pathway in human trophoblast <scp>JEG<\/scp>\u20103 cells"],"prefix":"10.1002","volume":"39","author":[{"given":"Yuting","family":"Chen","sequence":"first","affiliation":[{"name":"Dongguan Key Laboratory of Environmental Medicine, The First Dongguan Affiliated Hospital, School of Public Health 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