{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:45:46Z","timestamp":1788439546770,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica (PAPIIT)","award":["IN201422"],"award-info":[{"award-number":["IN201422"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Mono(2-ethylhexyl) phthalate (MEHP), a bioactive metabolite of di(2-ethylhexyl) phthalate (DEHP), has been detected in the placenta and urine of pregnant women and is linked to adverse pregnancy outcomes. However, its effects on mitochondrial homeostasis in trophoblast cells remain incompletely understood. This study examined the impact of MEHP (0.5\u2013200 \u00b5M) on mitochondrial function, dynamics, and biogenesis in human HTR-8\/SVneo trophoblast cells. MEHP (\u22655 \u00b5M) reduced MTT conversion without compromising membrane integrity, suggesting early metabolic or redox imbalance. A dose-dependent loss of mitochondrial membrane potential was observed, with increased reactive oxygen species (ROS) generation only at 200 \u00b5M. MEHP modulated the expression of mitochondrial dynamics genes, with a more pronounced mitofusin 1 (MFN1) induction at low doses and increased mitochondrial DNA content, suggesting a compensatory response to mild stress. Conversely, high doses more strongly induced fission and mitochondrial 1 (FIS1) expression, suggesting mitochondrial fragmentation. Both concentrations induced the expression of the mitochondrial biogenesis regulators peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1\u03b1) and nuclear factor erythroid 2\u2013related factor 2 (Nrf2), while sirtuin 1 (SIRT1) expression and activity declined progressively with dose. These results demonstrate that MEHP disrupts mitochondrial homeostasis in trophoblast cells at concentrations spanning the estimated human exposure range. The dose-dependent effects, from adaptive responses to overt dysfunction, may help explain the associations between MEHP exposure and placental pathology observed in epidemiological studies.<\/jats:p>","DOI":"10.3390\/toxics13090770","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T15:10:46Z","timestamp":1757603446000},"page":"770","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mono(2-ethylhexyl) Phthalate Disrupts Mitochondrial Function, Dynamics and Biogenesis in Human Trophoblast Cells at Human Exposure Range Concentrations"],"prefix":"10.3390","volume":"13","author":[{"given":"Luis","family":"Mart\u00ednez-Razo","sequence":"first","affiliation":[{"name":"Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"},{"name":"Servicio de Gen\u00e9tica, Hospital General de M\u00e9xico Dr. Eduardo Liceaga, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2659-6864","authenticated-orcid":false,"given":"Nadia","family":"Rivero-Segura","sequence":"additional","affiliation":[{"name":"Direcci\u00f3n de Investigaci\u00f3n, Instituto Nacional de Geriatr\u00eda, Mexico City 10200, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ericka","family":"Almeida-Aguirre","sequence":"additional","affiliation":[{"name":"Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael","family":"Mancilla-Herrera","sequence":"additional","affiliation":[{"name":"Departamento de Infectolog\u00eda e Inmunolog\u00eda, Instituto Nacional de Perinatolog\u00eda Isidro Espinosa de los Reyes, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5070-938X","authenticated-orcid":false,"given":"Ruth","family":"Rinc\u00f3n-Heredia","sequence":"additional","affiliation":[{"name":"Unidad de Imagenolog\u00eda, Instituto de Fisiolog\u00eda Celular, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04500, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4135-7933","authenticated-orcid":false,"given":"Alejandra","family":"Mart\u00ednez-Ibarra","sequence":"additional","affiliation":[{"name":"Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Cerb\u00f3n","sequence":"additional","affiliation":[{"name":"Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1007\/s40572-015-0065-9","article-title":"Trends in Exposure to Chemicals in Personal Care and Consumer Products","volume":"2","author":"Calafat","year":"2015","journal-title":"Curr. 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