{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:00:07Z","timestamp":1790434807420,"version":"4.1.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health"},{"name":"Human Development (NICHD) of the National Institutes of Health","award":["R00HD107262"],"award-info":[{"award-number":["R00HD107262"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants associated with placenta-mediated pregnancy complications, including preeclampsia, fetal growth restriction, and preterm birth. The syncytiotrophoblast (STB), which forms the placental barrier at the maternal\u2013fetal interface and is directly exposed to maternal blood, is a primary site of PFAS exposure. Although PFAS induce STB apoptosis, the upstream stress-signaling pathways involved remain poorly defined. Here, we investigated stress-responsive signaling mechanisms mediating PFAS-induced STB cell death. STB differentiated from human trophoblast stem cells were exposed to vehicle or an environmentally relevant mixture of 5 PFAS (perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorohexane sulfonate, perfluorononanoic acid, and perfluorodecanoic acid; 0.0138 to 34.5\u2009\u00b5M) for 3 or 6\u2009h. Cytotoxicity, apoptosis, mitochondrial membrane potential, and stress-signaling pathway activation were assessed by lactate dehydrogenase release, immunoblotting, JC-10 assay, and reverse transcription-quantitative PCR. PFAS mixtures did not induce cytotoxicity at 3\u2009h but significantly increased cytotoxicity at 6\u2009h at 34.5\u2009\u00b5M, coinciding with the induction of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, and NOXA. The pan-caspase inhibitor z-VAD-FMK prevented cytotoxicity, indicating caspase-dependent apoptosis. PFAS exposure reduced mitochondrial membrane potential and activated the integrated stress response (ISR), as evidenced by eukaryotic initiation factor 2\u03b1 phosphorylation, activating transcription factor 4 (ATF4) induction, and increased ATF4 target gene expression. In parallel, c-Jun N-terminal kinase (JNK) signaling was activated, as evidenced by JNK phosphorylation and induction of immediate-early genes (JUN, FOS, EGR1). Pharmacologic inhibition of the ISR modestly attenuated PFAS-induced cytotoxicity, whereas pharmacologic inhibition of JNK rescued cytotoxicity and apoptotic signaling. Together, these findings identify JNK-driven stress signaling as the dominant mediator of PFAS-induced STB apoptosis, with a secondary contribution from the ISR.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag060","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T11:44:20Z","timestamp":1779277460000},"source":"Crossref","is-referenced-by-count":0,"title":["Stress-activated pathways mediate PFAS effects on human placental syncytiotrophoblast cells"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2645-7431","authenticated-orcid":false,"given":"Keisuke","family":"Kozai","sequence":"first","affiliation":[{"name":"Fetal Health Center, Children\u2019s Mercy , Kansas City, MO 64108,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9672-4158","authenticated-orcid":false,"given":"Kaela M","family":"Varberg","sequence":"additional","affiliation":[{"name":"Fetal Health Center, Children\u2019s Mercy , Kansas City, MO 64108,","place":["United States"]},{"name":"Department of Pediatrics, University of Missouri Kansas City , Kansas City, MO 64108,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"issue":":","key":"2026092610252753200_kfag060-B1","doi-asserted-by":"publisher","first-page":"e202503523","DOI":"10.26508\/lsa.202503523","article-title":"The Janus framework of the integrated stress response: from homeostasis to maladaptation","volume":"9","author":"Altintas","year":"2026","journal-title":"Life Sci Alliance"},{"key":"2026092610252753200_kfag060-B2","doi-asserted-by":"publisher","DOI":"10.1007\/s40572-024-00464-5","article-title":"Effects of early-life pfas exposure on child neurodevelopment: a review of the evidence and research gaps","volume":"12","author":"Ames","year":"2025","journal-title":"Curr Envir Health Rpt"},{"key":"2026092610252753200_kfag060-B3","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.247353","article-title":"Mitochondrial dysfunction triggers a catabolic response in chondrocytes via ROS-mediated activation of the JNK\/AP1 pathway","volume":"133","author":"Ansari","year":"2020","journal-title":"J Cell Sci"},{"key":"2026092610252753200_kfag060-B4","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54954","article-title":"MARCH5 mediates NOXA-dependent MCL1 degradation driven by kinase inhibitors and integrated stress response activation","volume":"9","author":"Arai","year":"2020","journal-title":"Elife"},{"key":"2026092610252753200_kfag060-B5","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1038\/s41467-020-15051-z","article-title":"Electron transport chain activity is a predictor and target for venetoclax sensitivity in multiple myeloma","volume":"11","author":"Bajpai","year":"2020","journal-title":"Nat Commun"},{"key":"2026092610252753200_kfag060-B6","doi-asserted-by":"publisher","first-page":"8158","DOI":"10.1021\/acs.est.9b07102","article-title":"Identifying risk factors for levels of per- and polyfluoroalkyl substances (PFAS) in the placenta in a high-risk pregnancy cohort in North Carolina","volume":"54","author":"Bangma","year":"2020","journal-title":"Environ Sci Technol"},{"key":"2026092610252753200_kfag060-B7","doi-asserted-by":"publisher","first-page":"27006","DOI":"10.1289\/EHP6233","article-title":"Evaluation of maternal, embryo, and placental effects in CD-1 mice following gestational exposure to perfluorooctanoic acid (PFOA) or hexafluoropropylene oxide dimer acid (HFPO-DA or Genx)","volume":"128","author":"Blake","year":"2020","journal-title":"Environ Health Perspect"},{"key":"2026092610252753200_kfag060-B8","doi-asserted-by":"publisher","first-page":"152565","DOI":"10.1016\/j.tox.2020.152565","article-title":"Early life exposure to per- and polyfluoroalkyl substances (PFAS) and latent health outcomes: a review including the placenta as a target tissue and possible driver of peri- and postnatal effects","volume":"443","author":"Blake","year":"2020","journal-title":"Toxicology"},{"key":"2026092610252753200_kfag060-B9","doi-asserted-by":"publisher","first-page":"881347","DOI":"10.3389\/ftox.2022.881347","article-title":"A high-throughput toxicity screen of 42 per- and polyfluoroalkyl substances (PFAS) and functional assessment of migration and gene expression in human placental trophoblast cells","volume":"4","author":"Blake","year":"2022","journal-title":"Front Toxicol"},{"key":"2026092610252753200_kfag060-B10","doi-asserted-by":"publisher","first-page":"107004","DOI":"10.1289\/EHP9091","article-title":"Maternal levels of perfluoroalkyl substances (PFAS) during early pregnancy in relation to preeclampsia subtypes and biomarkers of preeclampsia risk","volume":"129","author":"Bommarito","year":"2021","journal-title":"Environ Health Perspect"},{"key":"2026092610252753200_kfag060-B11","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1002\/ieam.258","article-title":"Perfluoroalkyl and polyfluoroalkyl substances in the environment: terminology, classification, and origins","volume":"7","author":"Buck","year":"2011","journal-title":"Integr Environ Assess Manag"},{"key":"2026092610252753200_kfag060-B12","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.placenta.2021.05.002","article-title":"Syncytiotrophoblast stress in early onset preeclampsia: the issues perpetuating the syndrome","volume":"113","author":"Carrasco-Wong","year":"2021","journal-title":"Placenta"},{"key":"2026092610252753200_kfag060-B13","doi-asserted-by":"publisher","first-page":"123597","DOI":"10.1016\/j.envres.2025.123597","article-title":"Association between gestational PFAS exposure biomarkers and risk of preeclampsia in the ECHO cohort","volume":"292","author":"Cathey","year":"2026","journal-title":"Environ Res"},{"key":"2026092610252753200_kfag060-B14","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1741-7007-12-34","article-title":"Mitochondria as signaling organelles","volume":"12","author":"Chandel","year":"2014","journal-title":"BMC Biol"},{"key":"2026092610252753200_kfag060-B15","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1039\/d0em00355g","article-title":"The high persistence of PFAS is sufficient for their management as a chemical class","volume":"22","author":"Cousins","year":"2020","journal-title":"Environ Sci Process Impacts"},{"key":"2026092610252753200_kfag060-B16","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/s0092-8674(00)00116-1","article-title":"Signal transduction by the JNK group of map kinases","volume":"103","author":"Davis","year":"2000","journal-title":"Cell"},{"key":"2026092610252753200_kfag060-B17","doi-asserted-by":"publisher","first-page":"6245","DOI":"10.1038\/onc.2008.301","article-title":"JNK signaling in apoptosis","volume":"27","author":"Dhanasekaran","year":"2008","journal-title":"Oncogene"},{"key":"2026092610252753200_kfag060-B18","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1096\/fj.04-1505com","article-title":"Mitochondrial signals initiate the activation of c-Jun N-terminal kinase (JNK) by hypoxia-reoxygenation","volume":"18","author":"Dougherty","year":"2004","journal-title":"Faseb J"},{"key":"2026092610252753200_kfag060-B19","doi-asserted-by":"publisher","first-page":"113508","DOI":"10.1016\/j.ecoenv.2022.113508","article-title":"Perfluorooctanoic acid exposure increases both proliferation and apoptosis of human placental trophoblast cells mediated by er stress-induced ros or upr pathways","volume":"236","author":"Du","year":"2022","journal-title":"Ecotoxicol Environ Saf"},{"key":"2026092610252753200_kfag060-B20","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/s41586-020-2076-4","article-title":"A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol","volume":"579","author":"Fessler","year":"2020","journal-title":"Nature"},{"key":"2026092610252753200_kfag060-B21","doi-asserted-by":"publisher","first-page":"57002","DOI":"10.1289\/EHP5444","article-title":"Early life exposure to perfluoroalkyl substances (PFAS) and ADHD: a meta-analysis of nine European population-based studies","volume":"128","author":"Forns","year":"2020","journal-title":"Environ Health Perspect"},{"key":"2026092610252753200_kfag060-B22","doi-asserted-by":"publisher","first-page":"3740","DOI":"10.1016\/j.molcel.2023.09.026","article-title":"Mitochondrial DNA breaks activate an integrated stress response to reestablish homeostasis","volume":"83","author":"Fu","year":"2023","journal-title":"Mol Cell"},{"key":"2026092610252753200_kfag060-B23","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1017\/S2040174412000529","article-title":"Placental transport in response to altered maternal nutrition","volume":"4","author":"Gaccioli","year":"2013","journal-title":"J Dev Orig Health Dis"},{"key":"2026092610252753200_kfag060-B24","doi-asserted-by":"publisher","first-page":"116812","DOI":"10.1016\/j.envres.2023.116812","article-title":"Association between prenatal exposure to per- and polyfluoroalkyl substances and neurodevelopment in children: evidence based on birth cohort","volume":"236","author":"Gao","year":"2023","journal-title":"Environ Res"},{"key":"2026092610252753200_kfag060-B25","doi-asserted-by":"publisher","first-page":"855348","DOI":"10.3389\/fpubh.2022.855348","article-title":"Association between exposure to per- and polyfluoroalkyl substances and birth outcomes: a systematic review and meta-analysis","volume":"10","author":"Gui","year":"2022","journal-title":"Front Public Health"},{"key":"2026092610252753200_kfag060-B26","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/s41586-020-2078-2","article-title":"Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway","volume":"579","author":"Guo","year":"2020","journal-title":"Nature"},{"key":"2026092610252753200_kfag060-B27","doi-asserted-by":"publisher","first-page":"133873","DOI":"10.1016\/j.chemosphere.2022.133873","article-title":"Concentrations of per- and polyfluoroalkyl substances (PFAS) in human placental tissues and associations with birth outcomes","volume":"295","author":"Hall","year":"2022","journal-title":"Chemosphere"},{"key":"2026092610252753200_kfag060-B28","doi-asserted-by":"publisher","first-page":"108383","DOI":"10.1016\/j.reprotox.2023.108383","article-title":"Perfluorooctanoic acid induces cell death in TM3 cells via the ER stress-mitochondrial apoptosis pathway","volume":"118","author":"Han","year":"2023","journal-title":"Reprod Toxicol"},{"key":"2026092610252753200_kfag060-B29","doi-asserted-by":"publisher","first-page":"10715","DOI":"10.1021\/acs.est.4c14478","article-title":"A critical review of populations with occupational exposure to per- and polyfluoroalkyl substances: external exposome, internal exposure levels, and health effects","volume":"59","author":"He","year":"2025","journal-title":"Environ Sci Technol"},{"key":"2026092610252753200_kfag060-B30","doi-asserted-by":"publisher","first-page":"110901","DOI":"10.1016\/j.jbc.2025.110901","article-title":"Dissecting stress-activated protein kinase (SAPK)-signaling pathways using multiplex gene knockout HeLa cells","volume":"301","author":"Ito","year":"2025","journal-title":"J Biol Chem"},{"key":"2026092610252753200_kfag060-B31","doi-asserted-by":"publisher","first-page":"3479","DOI":"10.1007\/s00018-019-03104-6","article-title":"Human placenta and trophoblast development: key molecular mechanisms and model systems","volume":"76","author":"Knofler","year":"2019","journal-title":"Cell Mol Life Sci"},{"key":"2026092610252753200_kfag060-B32","doi-asserted-by":"publisher","first-page":"6158","DOI":"10.1038\/sj.onc.1203173","article-title":"Diverse functions of JNK signaling and c-Jun in stress response and apoptosis","volume":"18","author":"Leppa","year":"1999","journal-title":"Oncogene"},{"key":"2026092610252753200_kfag060-B33","doi-asserted-by":"publisher","first-page":"e039949","DOI":"10.1161\/JAHA.124.039949","article-title":"Prenatal per- and polyfluoroalkyl substance exposures and longitudinal blood pressure measurements in children aged 3 to 18 years: findings from a racially and ethnically diverse us birth cohort","volume":"14","author":"Li","year":"2025","journal-title":"J Am Heart Assoc"},{"key":"2026092610252753200_kfag060-B34","doi-asserted-by":"publisher","first-page":"115939","DOI":"10.1016\/j.ecoenv.2024.115939","article-title":"Association of prenatal exposure to perfluorinated and polyfluoroalkyl substances with childhood neurodevelopment: a systematic review and meta-analysis","volume":"271","author":"Liu","year":"2024","journal-title":"Ecotoxicol Environ Saf"},{"key":"2026092610252753200_kfag060-B35","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/sj.cr.7290262","article-title":"Role of JNK activation in apoptosis: a double-edged sword","volume":"15","author":"Liu","year":"2005","journal-title":"Cell Res"},{"key":"2026092610252753200_kfag060-B36","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.envint.2019.01.010","article-title":"Concentrations of perfluoroalkyl substances (PFASS) in human embryonic and fetal organs from first, second, and third trimester pregnancies","volume":"124","author":"Mamsen","year":"2019","journal-title":"Environ Int"},{"key":"2026092610252753200_kfag060-B37","doi-asserted-by":"publisher","first-page":"097018","DOI":"10.1289\/EHP1330","article-title":"Prenatal exposure to perfluoroalkyl substances and cardiometabolic risk in children from the Spanish INMA birth cohort study","volume":"125","author":"Manzano-Salgado","year":"2017","journal-title":"Environ Health Perspect"},{"key":"2026092610252753200_kfag060-B38","doi-asserted-by":"publisher","first-page":"1112253","DOI":"10.3389\/fnmol.2023.1112253","article-title":"A stay of execution: Atf4 regulation and potential outcomes for the integrated stress response","volume":"16","author":"Neill","year":"2023","journal-title":"Front Mol Neurosci"},{"key":"2026092610252753200_kfag060-B39","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.stem.2017.11.004","article-title":"Derivation of human trophoblast stem cells","volume":"22","author":"Okae","year":"2018","journal-title":"Cell Stem Cell"},{"key":"2026092610252753200_kfag060-B40","doi-asserted-by":"publisher","first-page":"37006","DOI":"10.1289\/EHP10723","article-title":"Birth outcomes in relation to prenatal exposure to per- and polyfluoroalkyl substances and stress in the environmental influences on child health outcomes (ECHO) program","volume":"131","author":"Padula","year":"2023","journal-title":"Environ Health Perspect"},{"key":"2026092610252753200_kfag060-B41","doi-asserted-by":"publisher","first-page":"106853","DOI":"10.1016\/j.envint.2021.106853","article-title":"Prenatal and postnatal exposure to PFAS and cardiometabolic factors and inflammation status in children from six European cohorts","volume":"157","author":"Papadopoulou","year":"2021","journal-title":"Environ Int"},{"key":"2026092610252753200_kfag060-B42","doi-asserted-by":"publisher","first-page":"122745","DOI":"10.1016\/j.envres.2025.122745","article-title":"Sex-dependent relationships between PFAS and placental transcriptomics identified by weighted gene co-expression analysis","volume":"286","author":"Perez","year":"2025","journal-title":"Environ Res"},{"key":"2026092610252753200_kfag060-B43","doi-asserted-by":"publisher","first-page":"120868","DOI":"10.1016\/j.envres.2025.120868","article-title":"Sex-specific effects of in utero exposure to per- and polyfluoroalkyl substances on placental development","volume":"270","author":"Perez","year":"2025","journal-title":"Environ Res"},{"key":"2026092610252753200_kfag060-B44","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.molmed.2014.01.005","article-title":"Mitochondrial pathology: stress signals from the energy factory","volume":"20","author":"Raimundo","year":"2014","journal-title":"Trends Mol Med"},{"key":"2026092610252753200_kfag060-B45","doi-asserted-by":"publisher","first-page":"S907","DOI":"10.1016\/j.ajog.2020.09.047","article-title":"Syncytiotrophoblast stress in preeclampsia: the convergence point for multiple pathways","volume":"226","author":"Redman","year":"2022","journal-title":"Am J Obstet Gynecol"},{"key":"2026092610252753200_kfag060-B46","doi-asserted-by":"publisher","first-page":"16774","DOI":"10.1021\/acs.est.4c06017","article-title":"Neurotoxic effects of mixtures of perfluoroalkyl substances (PFAS) at environmental and human blood concentrations","volume":"58","author":"Rios-Bonilla","year":"2024","journal-title":"Environ Sci Technol"},{"key":"2026092610252753200_kfag060-B47","doi-asserted-by":"publisher","first-page":"107151","DOI":"10.1016\/j.jbc.2024.107151","article-title":"The integrated stress response in metabolic adaptation","volume":"300","author":"Ryoo","year":"2024","journal-title":"J Biol Chem"},{"key":"2026092610252753200_kfag060-B48","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1093\/aje\/kwx332","article-title":"Early-pregnancy plasma concentrations of perfluoroalkyl substances and birth outcomes in project viva: confounded by pregnancy hemodynamics?","volume":"187","author":"Sagiv","year":"2018","journal-title":"Am J Epidemiol"},{"key":"2026092610252753200_kfag060-B49","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1038\/s41418-025-01618-0","article-title":"Targeting prohibitins activates the ISR through DELE1-HRI by impairing protein import into the mitochondrial matrix","volume":"33","author":"Sanchez-Vera","year":"2026","journal-title":"Cell Death Differ"},{"key":"2026092610252753200_kfag060-B50","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1128\/MCB.19.4.2435","article-title":"Mitogen-activated protein kinases: specific messages from ubiquitous messengers","volume":"19","author":"Schaeffer","year":"1999","journal-title":"Mol Cell Biol"},{"key":"2026092610252753200_kfag060-B51","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1111\/j.1600-0897.2010.00837.x","article-title":"Placental apoptosis in health and disease","volume":"64","author":"Sharp","year":"2010","journal-title":"Am J Reprod Immunol"},{"key":"2026092610252753200_kfag060-B52","doi-asserted-by":"publisher","first-page":"3431","DOI":"10.1113\/jphysiol.2009.172403","article-title":"Understanding placental nutrient transfer\u2014why bother? New biomarkers of fetal growth","volume":"587","author":"Sibley","year":"2009","journal-title":"J Physiol"},{"key":"2026092610252753200_kfag060-B53","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1093\/biolre\/ioy049","article-title":"Hemochorial placentation: development, function, and adaptations","volume":"99","author":"Soares","year":"2018","journal-title":"Biol Reprod"},{"key":"2026092610252753200_kfag060-B54","doi-asserted-by":"publisher","first-page":"2176","DOI":"10.1074\/jbc.M808844200","article-title":"Mitochondrial complex III-generated oxidants activate ASK1 and JNK to induce alveolar epithelial cell death following exposure to particulate matter air pollution","volume":"284","author":"Soberanes","year":"2009","journal-title":"J Biol Chem"},{"key":"2026092610252753200_kfag060-B55","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41366-023-01420-3","article-title":"Prenatal exposure to per- and polyfluoroalkyl substances and early childhood adiposity and cardiometabolic health in the healthy start study","volume":"48","author":"Starling","year":"2024","journal-title":"Int J Obes (Lond)"},{"key":"2026092610252753200_kfag060-B56","doi-asserted-by":"publisher","first-page":"106821","DOI":"10.1016\/j.ntt.2019.106821","article-title":"Ros-mediated JNK pathway critically contributes to PFOS-triggered apoptosis in SH-SY5Y cells","volume":"75","author":"Sun","year":"2019","journal-title":"Neurotoxicol Teratol"},{"key":"2026092610252753200_kfag060-B57","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41370-018-0094-1","article-title":"A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASS) and present understanding of health effects","volume":"29","author":"Sunderland","year":"2019","journal-title":"J Expo Sci Environ Epidemiol"},{"key":"2026092610252753200_kfag060-B58","doi-asserted-by":"publisher","first-page":"2871","DOI":"10.1128\/MCB.23.8.2871-2882.2003","article-title":"c-Jun NH(2)-terminal kinase is essential for the regulation of AP-1 by tumor necrosis factor","volume":"23","author":"Ventura","year":"2003","journal-title":"Mol Cell Biol"},{"key":"2026092610252753200_kfag060-B59","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1093\/biolre\/iox012","article-title":"Placental transporter localization and expression in the human: the importance of species, sex, and gestational age differences","volume":"96","author":"Walker","year":"2017","journal-title":"Biol Reprod"},{"key":"2026092610252753200_kfag060-B60","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s001090050063","article-title":"Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways","volume":"74","author":"Whitmarsh","year":"1996","journal-title":"J Mol Med (Berl)"},{"key":"2026092610252753200_kfag060-B61","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1038\/s41390-019-0720-1","article-title":"Maternal serum levels of perfluoroalkyl substances in early pregnancy and offspring birth weight","volume":"87","author":"Wikstrom","year":"2020","journal-title":"Pediatr Res"},{"key":"2026092610252753200_kfag060-B62","doi-asserted-by":"publisher","first-page":"3321","DOI":"10.1016\/j.molcel.2022.07.012","article-title":"Stressed to death: mitochondrial stress responses connect respiration and apoptosis in cancer","volume":"82","author":"Winter","year":"2022","journal-title":"Mol Cell"},{"key":"2026092610252753200_kfag060-B63","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1093\/annhyg\/mes023","article-title":"Retrospective exposure assessment of perfluorooctanoic acid serum concentrations at a fluoropolymer manufacturing plant","volume":"56","author":"Woskie","year":"2012","journal-title":"Ann Occup Hyg"},{"key":"2026092610252753200_kfag060-B64","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1084\/jem.182.2.367","article-title":"Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death","volume":"182","author":"Zamzami","year":"1995","journal-title":"J Exp Med"},{"key":"2026092610252753200_kfag060-B65","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/0014-5793(96)00280-3","article-title":"Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis","volume":"384","author":"Zamzami","year":"1996","journal-title":"FEBS Lett"},{"key":"2026092610252753200_kfag060-B66","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1084\/jem.181.5.1661","article-title":"Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo","volume":"181","author":"Zamzami","year":"1995","journal-title":"J Exp Med"},{"key":"2026092610252753200_kfag060-B67","doi-asserted-by":"publisher","first-page":"e70105","DOI":"10.1002\/cph4.70105","article-title":"The integrated stress response in cancer: paradox and therapeutic promise","volume":"16","author":"Zhang","year":"2026","journal-title":"Compr Physiol"},{"key":"2026092610252753200_kfag060-B68","doi-asserted-by":"publisher","first-page":"127002","DOI":"10.1289\/EHP12597","article-title":"Associations of prenatal per- and polyfluoroalkyl substance (pfas) exposures with offspring adiposity and body composition at 16-20 years of age: project viva","volume":"131","author":"Zhang","year":"2023","journal-title":"Environ Health Perspect"},{"key":"2026092610252753200_kfag060-B69","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.placenta.2015.02.008","article-title":"Reduction of progesterone, estradiol and hcg secretion by perfluorooctane sulfonate via induction of apoptosis in human placental syncytiotrophoblasts","volume":"36","author":"Zhang","year":"2015","journal-title":"Placenta"},{"key":"2026092610252753200_kfag060-B70","doi-asserted-by":"publisher","first-page":"114256","DOI":"10.1016\/j.ecoenv.2022.114256","article-title":"Perfluorooctane sulfonate exposure induces preeclampsia-like syndromes by damaging trophoblast mitochondria in pregnant mice","volume":"247","author":"Zhao","year":"2022","journal-title":"Ecotoxicol Environ Saf"},{"key":"2026092610252753200_kfag060-B71","doi-asserted-by":"publisher","first-page":"3864","DOI":"10.1021\/es4057467","article-title":"Highly elevated serum concentrations of perfluoroalkyl substances in fishery employees from tangxun lake, China","volume":"48","author":"Zhou","year":"2014","journal-title":"Environ Sci Technol"},{"key":"2026092610252753200_kfag060-B72","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/jat.3119","article-title":"Involvement of mitogen-activated protein kinase and NF-\u03ba\u03b2 signaling pathways in perfluorooctane sulfonic acid-induced inflammatory reaction in BV2 microglial cells","volume":"35","author":"Zhu","year":"2015","journal-title":"J Appl Toxicol"},{"key":"2026092610252753200_kfag060-B73","doi-asserted-by":"publisher","first-page":"154352","DOI":"10.1016\/j.tox.2025.154352","article-title":"A meta-analysis-based adverse outcome pathway for the reproductive toxicity induced by per- and poly-fluoroalkyl substances in animals","volume":"520","author":"Zhu","year":"2026","journal-title":"Toxicology"}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfag060\/68371046\/kfag060.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/209\/6\/kfag060\/68371046\/kfag060.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/209\/6\/kfag060\/68371046\/kfag060.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:25:32Z","timestamp":1790432732000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/doi\/10.1093\/toxsci\/kfag060\/8690978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":73,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,5]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfag060","relation":{},"ISSN":["1096-0929"],"issn-type":[{"value":"1096-0929","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,5,22]]},"article-number":"kfag060"}}