{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T12:13:47Z","timestamp":1756901627203,"version":"3.44.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Korea Ministry of Environment","award":["2480000070"],"award-info":[{"award-number":["2480000070"]}]},{"name":"Korea Institute of Toxicology, Republic of Korea","award":["KK-2502-01","KK-2504"],"award-info":[{"award-number":["KK-2502-01","KK-2504"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bisphenol A (BPA), widely used in plastics and resins, has raised health concerns for its endocrine-disrupting effects. BPA analogues such as bisphenol S (BPS) and bisphenol F (BPF) emerged as alternatives but exhibit similar risks. Despite regulations on BPA in many countries, alternatives remain insufficiently controlled. Although the safety of BPS and BPF has not been sufficiently verified, these compounds have already been detected in various environmental sources and human urine, raising serious concerns. While bisphenols are expected to have various adverse effects, research remains limited. This study investigates the adverse effects of bisphenols mixture on rats from fetal stage to young adulthood by analyzing transcriptomes in multiple tissues\u2014liver, kidney, thyroid gland, and reproductive organs\u2014and by gender, to identify key genes affected by bisphenol exposure. Dams were orally administered test substances from gestational day 6 to lactation day 6, and F1 pups received the same substances at half the concentration from postnatal day 7 to day 63. Transcriptome analysis of the collected tissues identified core genes related to high-density lipoprotein metabolism and hormone secretion, providing insights into mechanisms through which BPA may disrupt hormonal balance. Furthermore, the study suggests that combined exposure to BPA, BPS, and BPF produces distinct effects compared to BPA alone, with pronounced impacts on the thyroid and reproductive organs, despite individual concentrations being below the no-observed-adverse-effect-level. These findings highlight the potential cumulative impact of endocrine disrupting chemicals in the body.<\/jats:p>","DOI":"10.1093\/toxres\/tfaf120","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T20:39:24Z","timestamp":1755549564000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrated transcriptome analysis of rats exposed to bisphenol mixtures from the fetal to developmental stage"],"prefix":"10.1093","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-5510","authenticated-orcid":false,"given":"Soontag","family":"Jung","sequence":"first","affiliation":[{"name":"Laboratory of Developmental and Reproductive Toxicology , Korea Institute of Toxicology, Yuseonggu, Daejeon 34114 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixian","family":"Quah","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental and Reproductive Toxicology , Korea Institute of Toxicology, Yuseonggu, Daejeon 34114 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Onju","family":"Ham","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental and Reproductive Toxicology , Korea Institute of Toxicology, Yuseonggu, Daejeon 34114 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental and Reproductive Toxicology , Korea Institute of Toxicology, Yuseonggu, Daejeon 34114 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Seong","family":"Jeong","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental and Reproductive Toxicology , Korea Institute of Toxicology, Yuseonggu, Daejeon 34114 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woojin","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental and Reproductive Toxicology , Korea Institute of Toxicology, Yuseonggu, Daejeon 34114 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7109-6423","authenticated-orcid":false,"given":"Seung-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental and Reproductive Toxicology , Korea Institute of Toxicology, Yuseonggu, Daejeon 34114 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wook-Joon","family":"Yu","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental and Reproductive Toxicology , Korea Institute of Toxicology, Yuseonggu, Daejeon 34114 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"volume-title":"Joint FAO\/WHO expert meeting to review toxicological and health aspects of bisphenol a: final report, including report of stakeholder meeting on bisphenol a, 1\u20135 November 2010","year":"2011","author":"WHO","key":"2025081816391636600_ref1"},{"key":"2025081816391636600_ref2","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1515\/reveh-2019-0034","article-title":"A review on sources and health impacts of bisphenol a","volume":"35","author":"Abraham","year":"2020","journal-title":"Rev Environ Health"},{"key":"2025081816391636600_ref3","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0303-7207(98)00084-7","article-title":"Bisphenol a interacts with the estrogen receptor \u03b1 in a distinct manner from estradiol","volume":"142","author":"Gould","year":"1998","journal-title":"Mol Cell Endocrinol"},{"key":"2025081816391636600_ref4","doi-asserted-by":"publisher","first-page":"4252","DOI":"10.1210\/endo.139.10.6216","article-title":"Interaction of estrogenic chemicals and phytoestrogens with Estrogen receptor \u03b2","volume":"139","author":"Kuiper","year":"1998","journal-title":"Endocrinology."},{"key":"2025081816391636600_ref5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.reprotox.2007.07.010","article-title":"Human exposure to bisphenol a (BPA)","volume":"24","author":"Vandenberg","year":"2007","journal-title":"Reprod Toxicol"},{"key":"2025081816391636600_ref6","doi-asserted-by":"publisher","first-page":"2839","DOI":"10.1093\/humrep\/17.11.2839","article-title":"Determination of bisphenol a concentrations in human biological fluids reveals significant early prenatal exposure","volume":"17","author":"Ikezuki","year":"2002","journal-title":"Hum Reprod"},{"key":"2025081816391636600_ref7","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/S0890-6238(02)00051-5","article-title":"Maternal serum and amniotic fluid bisphenol a concentrations in the early second trimester","volume":"16","author":"Yamada","year":"2002","journal-title":"Reprod Toxicol"},{"key":"2025081816391636600_ref8","article-title":"NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol a","volume":"22","author":"Shelby","year":"2008","journal-title":"Ntp cerhr mon"},{"key":"2025081816391636600_ref9","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1177\/2165079915623790","article-title":"Bisphenol a: understanding the controversy","volume":"64","author":"Metz","year":"2016","journal-title":"Workplace Health Saf"},{"key":"2025081816391636600_ref10","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1289\/ehp.0901716","article-title":"Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to Bisphenol a","volume":"118","author":"Vandenberg","year":"2010","journal-title":"Environ Health Perspect"},{"key":"2025081816391636600_ref11","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/toxsci\/kfi074","article-title":"Comparative study of the endocrine-disrupting activity of Bisphenol a and 19 related compounds","volume":"84","author":"Kitamura","year":"2005","journal-title":"Toxicol Sci"},{"key":"2025081816391636600_ref12","doi-asserted-by":"publisher","first-page":"5438","DOI":"10.1021\/acs.est.5b05387","article-title":"Bisphenol analogues other than BPA: environmental occurrence, human exposure, and toxicity-a review","volume":"50","author":"Chen","year":"2016","journal-title":"Environ Sci Technol"},{"volume-title":"Aggregated risk assessment for bisphenols: bisphenol a, bisphenol F, bisphenol S","author":"NIFDS","key":"2025081816391636600_ref13"},{"key":"2025081816391636600_ref14","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1289\/ehp.1408989","article-title":"Bisphenol S and F: a systematic review and comparison of the hormonal activity of Bisphenol a substitutes","volume":"123","author":"Rochester","year":"2015","journal-title":"Environ Health Perspect"},{"key":"2025081816391636600_ref15","doi-asserted-by":"publisher","first-page":"152235","DOI":"10.1016\/j.tox.2019.06.006","article-title":"A scoping review of the health and toxicological activity of bisphenol a (BPA) structural analogues and functional alternatives","volume":"424","author":"Pelch","year":"2019","journal-title":"Toxicology."},{"key":"2025081816391636600_ref16","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.jchromb.2013.11.009","article-title":"Automated on-line column-switching high performance liquid chromatography isotope dilution tandem mass spectrometry method for the quantification of bisphenol a, bisphenol F, bisphenol S, and 11 other phenols in urine","volume":"944","author":"Zhou","year":"2014","journal-title":"J Chromatogr B"},{"key":"2025081816391636600_ref17","doi-asserted-by":"publisher","first-page":"121818","DOI":"10.1016\/j.envpol.2023.121818","article-title":"Cumulative and potential synergistic effects of seven different bisphenols on human granulosa cells in vitro?","volume":"330","author":"Lebachelier de la Riviere","year":"2023","journal-title":"Environ Pollut"},{"key":"2025081816391636600_ref18","doi-asserted-by":"publisher","first-page":"120908","DOI":"10.1016\/j.jhazmat.2019.120908","article-title":"Evaluation of single and combined toxicity of bisphenol a and its analogues using a highly-sensitive micro-biosensor","volume":"381","author":"Zhu","year":"2020","journal-title":"J Hazard Mater"},{"key":"2025081816391636600_ref19","doi-asserted-by":"publisher","first-page":"144286","DOI":"10.1016\/j.scitotenv.2020.144286","article-title":"Identification of synergistic and antagonistic actions of environmental pollutants: Bisphenols a, S and F in the presence of DEP, DBP, BADGE and BADGE\u00b72HCl in three component mixtures","volume":"767","author":"Jatkowska","year":"2021","journal-title":"Sci Total Environ"},{"key":"2025081816391636600_ref20","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3390\/ijerph17010112","article-title":"Bisphenols as a legacy pollutant, and their effects on organ vulnerability","volume":"17","author":"Kim","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"2025081816391636600_ref21","doi-asserted-by":"publisher","first-page":"2654","DOI":"10.3390\/ijerph17082654","article-title":"Bisphenols as environmental triggers of thyroid dysfunction: clues and evidence","volume":"17","author":"Gorini","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"2025081816391636600_ref22","doi-asserted-by":"publisher","first-page":"155","DOI":"10.5772\/62455","volume-title":"Environmental health risk-hazardous factors to living species","author":"Erkekoglu","year":"2016"},{"key":"2025081816391636600_ref23","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1093\/toxsci\/68.1.121","article-title":"Three-generation reproductive toxicity study of dietary Bisphenol a in CD Sprague-Dawley rats","volume":"68","author":"Tyl","year":"2002","journal-title":"Toxicol Sci"},{"key":"2025081816391636600_ref24","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1080\/10915810600961531","article-title":"Nonclinical vehicle use in studies by multiple routes in multiple species","volume":"25","author":"Gad","year":"2006","journal-title":"Int J Toxicol"},{"key":"2025081816391636600_ref25","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1093\/bioinformatics\/btn482","article-title":"Combining partial correlation and an information theory approach to the reversed engineering of gene co-expression networks","volume":"24","author":"Reverter","year":"2008","journal-title":"Bioinformatics."},{"key":"2025081816391636600_ref26","doi-asserted-by":"publisher","first-page":"8227314","DOI":"10.1155\/2022\/8227314","article-title":"Adverse effects of Bisphenol a on the liver and its underlying mechanisms: evidence from In vivo and In vitro studies","volume":"2022","author":"Abdulhameed","year":"2022","journal-title":"Biomed Res Int"},{"key":"2025081816391636600_ref27","doi-asserted-by":"publisher","first-page":"16231","DOI":"10.1007\/s11356-020-08041-7","article-title":"The effects of melatonin on possible damage that will occur on adipocytokines and liver tissue by coadministration of fructose and bisphenol a (BPA)","volume":"27","author":"Ak\u00e7ay","year":"2020","journal-title":"Environ Sci Pollut Res"},{"key":"2025081816391636600_ref28","doi-asserted-by":"publisher","first-page":"3220","DOI":"10.1039\/C8FO00248G","article-title":"Oleuropein and hydroxytyrosol rich extracts from olive leaves attenuate liver injury and lipid metabolism disturbance in bisphenol A-treated rats","volume":"9","author":"Mahmoudi","year":"2018","journal-title":"Food Funct"},{"key":"2025081816391636600_ref29","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1093\/ckj\/sfaa071","article-title":"Bisphenol S is a haemodialysis-associated xenobiotic that is less toxic than bisphenol a","volume":"14","author":"Mas","year":"2020","journal-title":"Clin Kidney J"},{"key":"2025081816391636600_ref30","doi-asserted-by":"publisher","first-page":"109684","DOI":"10.1016\/j.ecoenv.2019.109684","article-title":"Bisphenol a analogs in patients with chronic kidney disease and dialysis therapy","volume":"185","author":"Shen","year":"2019","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025081816391636600_ref31","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12940-017-0259-8","article-title":"Prenatal bisphenol a exposure and dysregulation of infant hypothalamic-pituitary-adrenal axis function: findings from the APrON cohort study","volume":"16","author":"Giesbrecht","year":"2017","journal-title":"Environ Health"},{"key":"2025081816391636600_ref32","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3961\/jpmph.20.310","article-title":"Associations between thyroid hormone levels and urinary concentrations of Bisphenol a, F, and S in 6-year-old children in Korea","volume":"54","author":"Jang","year":"2021","journal-title":"J Prev Med Public Health"},{"key":"2025081816391636600_ref33","doi-asserted-by":"publisher","first-page":"168","DOI":"10.3390\/nu14010168","article-title":"The impact of Bisphenol a on thyroid function in neonates and children: a systematic review of the literature","volume":"14","author":"Koutaki","year":"2022","journal-title":"Nutrients."},{"key":"2025081816391636600_ref34","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1080\/15376516.2019.1652873","article-title":"Exposure of BPA and its alternatives like BPB, BPF, and BPS impair subsequent reproductive potentials in adult female Sprague Dawley rats","volume":"30","author":"Ijaz","year":"2020","journal-title":"Toxicol Mech Methods"},{"key":"2025081816391636600_ref35","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.reprotox.2015.12.004","article-title":"The effects of in utero bisphenol a exposure on the ovaries in multiple generations of mice","volume":"60","author":"Berger","year":"2016","journal-title":"Reprod Toxicol"},{"key":"2025081816391636600_ref36","doi-asserted-by":"publisher","first-page":"124935","DOI":"10.1016\/j.chemosphere.2019.124935","article-title":"Bisphenol a disturbs transcription of steroidogenic genes in ovary of rare minnow Gobiocypris rarus via the abnormal DNA and histone methylation","volume":"240","author":"Liu","year":"2020","journal-title":"Chemosphere."},{"key":"2025081816391636600_ref37","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.mce.2006.04.033","article-title":"Endocrine disruptors and reproductive health: the case of bisphenol-a","volume":"254-255","author":"Maffini","year":"2006","journal-title":"Mol Cell Endocrinol"},{"key":"2025081816391636600_ref38","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1093\/toxsci\/kfu022","article-title":"Toxicity evaluation of Bisphenol a administered by gavage to Sprague Dawley rats from gestation day 6 through postnatal day 90","volume":"139","author":"Delclos","year":"2014","journal-title":"Toxicol Sci"},{"key":"2025081816391636600_ref39","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1210\/er.2011-1050","article-title":"Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses","volume":"33","author":"Vandenberg","year":"2012","journal-title":"Endocr Rev"},{"key":"2025081816391636600_ref40","first-page":"2397","volume-title":"Assessment of new information on Bisphenol S (BPS) submitted in response to the decision 1 under REACH regulation (EC) No 1907\/2006","author":"EFSA","year":"2020"},{"key":"2025081816391636600_ref41","doi-asserted-by":"publisher","first-page":"165711","DOI":"10.1016\/j.scitotenv.2023.165711","article-title":"Bisphenol analogues induce thyroid dysfunction via the disruption of the thyroid hormone synthesis pathway","volume":"900","author":"Hu","year":"2023","journal-title":"Sci Total Environ"},{"key":"2025081816391636600_ref42","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.3390\/ijerph14091044","article-title":"The effect of Bisphenol a on puberty: a critical review of the medical literature","volume":"14","author":"Leonardi","year":"2017","journal-title":"Int J Environ Res Public Health"},{"key":"2025081816391636600_ref43","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s40272-015-0130-8","article-title":"Central precocious puberty: update on diagnosis and treatment","volume":"17","author":"Chen","year":"2015","journal-title":"Paediatr Drugs"},{"key":"2025081816391636600_ref44","doi-asserted-by":"publisher","first-page":"112849","DOI":"10.1016\/j.ecoenv.2021.112849","article-title":"Binding and activity of bisphenol analogues to human peroxisome proliferator-activated receptor \u03b2\/\u03b4","volume":"226","author":"Li","year":"2021","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025081816391636600_ref45","doi-asserted-by":"publisher","first-page":"38","DOI":"10.22037\/uj.v0i0.3954","article-title":"Comparison of the effects of Clofibrate and Silafibrate on sperm parameters quality and sex hormones in male rats","volume":"15","author":"Delashoub","year":"2018","journal-title":"Urol J"},{"key":"2025081816391636600_ref46","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1289\/ehp.00108s3491","article-title":"Critical windows of exposure for children's health: the reproductive system in animals and humans","volume":"108","author":"Pryor","year":"2000","journal-title":"Environ Health Perspect"},{"key":"2025081816391636600_ref47","doi-asserted-by":"publisher","first-page":"11315","DOI":"10.1038\/s41598-018-29732-9","article-title":"Prenatal Bisphenol a exposure is linked to epigenetic changes in glutamate receptor subunit gene Grin2b in female rats and humans","volume":"8","author":"Alavian-Ghavanini","year":"2018","journal-title":"Sci Rep"},{"key":"2025081816391636600_ref48","doi-asserted-by":"publisher","first-page":"9738","DOI":"10.1093\/nar\/gkab697","article-title":"Epigenetic remodelling of enhancers in response to estrogen deprivation and re-stimulation","volume":"49","author":"Sklias","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2025081816391636600_ref49","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.taap.2013.05.015","article-title":"In vitro study on the agonistic and antagonistic activities of bisphenol-S and other bisphenol-a congeners and derivatives via nuclear receptors","volume":"272","author":"Molina-Molina","year":"2013","journal-title":"Toxicol Appl Pharmacol"},{"key":"2025081816391636600_ref50","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fphys.2021.761910","article-title":"KCNQ1 Potassium Channel expressed in human sperm is involved in sperm motility, acrosome reaction, protein tyrosine phosphorylation, and ion homeostasis during capacitation","volume":"12","author":"Gao","year":"2021","journal-title":"Front Physiol"},{"key":"2025081816391636600_ref51","doi-asserted-by":"publisher","first-page":"194829","DOI":"10.1155\/2012\/194829","article-title":"Bisphenol a induces hepatotoxicity through oxidative stress in rat model","volume":"2012","author":"Hassan","year":"2012","journal-title":"Oxidative Med Cell Longev"}],"container-title":["Toxicology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/14\/4\/tfaf120\/64079633\/tfaf120.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/14\/4\/tfaf120\/64079633\/tfaf120.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T20:39:25Z","timestamp":1755549565000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxres\/article\/doi\/10.1093\/toxres\/tfaf120\/8237551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,5]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7,5]]}},"URL":"https:\/\/doi.org\/10.1093\/toxres\/tfaf120","relation":{},"ISSN":["2045-4538"],"issn-type":[{"type":"electronic","value":"2045-4538"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,7,5]]},"article-number":"tfaf120"}}