{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:03:32Z","timestamp":1790647412319,"version":"4.1.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Michigan Center on Lifestage Environmental Exposures and Disease P30 Center","award":["NIEHS T32"],"award-info":[{"award-number":["NIEHS T32"]}]},{"name":"Michigan Center on Lifestage Environmental Exposures and Disease P30 Center","award":["ES007062"],"award-info":[{"award-number":["ES007062"]}]},{"name":"Michigan Center on Lifestage Environmental Exposures and Disease P30 Center","award":["NIEHS R01"],"award-info":[{"award-number":["NIEHS R01"]}]},{"name":"Michigan Center on Lifestage Environmental Exposures and Disease P30 Center","award":["ES028802"],"award-info":[{"award-number":["ES028802"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2002<\/jats:title>\n                    <jats:p>Exposure to per and polyfluoroalkyl substances (PFAS) is linked to various cardiovascular diseases (CVDs), but effects of developmental PFAS exposures on the human heart remain unclear. Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), the objective of this study was to investigate the effects of PFAS exposure during cardiac differentiation on gene expression and function of cardiomyocytes. We exposed 2 hiPSC lines (1 male and 1 female donor) to perfluorooctanoic acid (PFOA), a common and ubiquitous PFAS (0.05, 0.5, 5, 50, 100, 150, 200\u2009\u03bcM), followed by assessment of cellular number and pluripotency marker expression. PFOA exposure for 72\u2009h had no significant effects on hiPSC pluripotency, and modest inhibition of proliferation was observed only at the highest concentration. hiPSCs were then differentiated into ventricular cardiomyocytes in the continued presence or absence of PFOA using an established protocol. Optical mapping studies revealed dose and cell line-specific effects of PFOA on cardiomyocyte voltage and calcium dynamics that were still present 10\u2009d after cessation of exposure. Patch-clamping studies demonstrated small but significant reductions in repolarizing IKr currents with 5\u2009\u00b5M PFOA exposure in cardiomyocytes from both donors. Using RNA-seq, we found that exposure to PFOA led to significant changes in transcriptional pathways related to lipids and lipoproteins in the female hiPSC-CM, and developmental pathways and calcium homeostasis in the male hiPSC-CM. These findings provide direct experimental evidence that transient developmental exposure to PFOA can durably reprogram human cardiomyocyte gene expression and function, supporting a developmental origin of PFAS-associated cardiovascular disease risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact Statement<\/jats:title>\n                    <jats:p>These studies demonstrate that exposure to environmentally relevant levels of PFOA during the differentiation of hiPSCs into cardiomyocytes alters cardiac gene expression and function, with effects that persist beyond cessation of exposure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/toxsci\/kfag107","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T11:43:56Z","timestamp":1787399036000},"source":"Crossref","is-referenced-by-count":0,"title":["Acute exposure to perfluorooctanoic acid during cardiomyogenesis disrupts transcriptional and electrophysiological profiles in differentiated myocytes"],"prefix":"10.1093","volume":"209","author":[{"given":"Tomoko","family":"Ishikawa","sequence":"first","affiliation":[{"name":"Department of Environmental Health Sciences, School of Public Health, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, School of Public Health, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anagha","family":"Tapaswi","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, School of Public Health, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley E","family":"Sala-Hamrick","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, School of Public Health, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd J","family":"Herron","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical School, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]},{"name":"Greenstone Biosciences , Palo Alto, CA 94304,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-491X","authenticated-orcid":false,"given":"Eric N","family":"Jimenez Vazquez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhilasha","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical School, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]},{"name":"Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin A","family":"Colacino","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, School of Public Health, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]},{"name":"Department of Nutritional Sciences, School of Public Health, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3324-3773","authenticated-orcid":false,"given":"Andre","family":"Monteiro Da Rocha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical School, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0003-4513","authenticated-orcid":false,"given":"Laurie K","family":"Svoboda","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, School of Public Health, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]},{"name":"Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, MI 48109,","place":["United 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