{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:29:22Z","timestamp":1787027362144,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Bisphenol S (BPS) is among the most commonly used substitutes for Bisphenol A (BPA), an endocrine disrupting chemical used as a plasticizer in the manufacture of polycarbonate plastics and epoxy resins. Bisphenols interfere with estrogen receptor (ER) signaling, which modulates vascular function through stimulation of nitric oxide (NO) production\n                    <jats:italic>via<\/jats:italic>\n                    endothelial nitric oxide synthase (eNOS). BPS can cross into the placenta and accumulates in the fetal compartment to a greater extent than BPA, potentially interfering with key developmental events. Little is known regarding the developmental impact of exposure to BPA substitutes, particularly with respect to the vasculature.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    To determine if prenatal BPS exposure influences vascular health in adulthood.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    At the time of mating, female C57BL\/6\u00a0dams were administered BPS (250\u00a0nM) or vehicle control in the drinking water, and exposure continued during lactation. At 12-week of age, mesenteric arteries were excised from male and female offspring and assessed for responses to an endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) vasodilator. Endothelium-dependent dilation was measured in the presence or absence of L-NAME, an eNOS inhibitor. To further explore the role of NO and ER signaling, wire myography was used to assess ACh responses in aortic rings after acute exposure to BPS in the presence or absence of L-NAME or an ER antagonist.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Increased ACh dilation and increased sensitivity to Phe were observed in microvessels from BPS-exposed females, while no changes were observed in male offspring. Differences in ACh-induced dilation between control or BPS-exposed females were eliminated with L-NAME. Increased dilatory responses to ACh after acute BPS exposure were observed in aortic rings from female mice only, and differences were eliminated with inhibition of eNOS or inhibition of ER.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Prenatal BPS exposure leads to persistent changes in endothelium-dependent vascular function in a sex-specific manner that appears to be modulated by interaction of BPS with ER signaling.\n                  <\/jats:p>","DOI":"10.3389\/ftox.2022.933572","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T03:09:16Z","timestamp":1665630556000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspring"],"prefix":"10.3389","volume":"4","author":[{"given":"Liam T.","family":"Connors","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Lei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manvir","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radha D.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Easson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia B.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid R.","family":"Habibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Cole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"138759","DOI":"10.1016\/j.scitotenv.2020.138759","article-title":"Adipogenic effects of prenatal exposure to bisphenol S (BPS) in adult F1 male mice","volume":"728","author":"Ahn","year":"2020","journal-title":"Sci. Total Environ."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1289\/ehp.1001993","article-title":"Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring","volume":"118","author":"Alonso-Magdalena","year":"2010","journal-title":"Environ. Health Perspect."},{"key":"B3","volume-title":"Updated safety assessment of Bisphenol A (BPA) for use in food contact applications","author":"Aungst","year":"2014"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e33814","DOI":"10.1371\/journal.pone.0033814","article-title":"Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult male mice","volume":"7","author":"Batista","year":"2012","journal-title":"PLoS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1097\/MOP.0b013e3283445675","article-title":"Bisphenol A and children's health.","volume":"23","author":"Braun","year":"2011","journal-title":"Curr. Opin. Pediatr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"626448","DOI":"10.3389\/fphar.2020.626448","article-title":"Plasticizers and cardiovascular health: Role of adipose tissue dysfunction","volume":"11","author":"Callaghan","year":"2021","journal-title":"Front. Pharmacol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1210\/mend.16.5.0827","article-title":"ERbeta has nongenomic action in caveolae","volume":"16","author":"Chambliss","year":"2002","journal-title":"Mol. Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1530\/REP-13-0377","article-title":"Low-dose effects of bisphenol A on early sexual development in male and female rats","volume":"147","author":"Christiansen","year":"2014","journal-title":"Reproduction"},{"key":"B9","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1161\/hh0402.105096","article-title":"Estradiol alters nitric oxide production in the mouse aorta through the alpha-but not beta-estrogen receptor","volume":"90","author":"Darblade","year":"2002","journal-title":"Circ. Res"},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.2139\/ssrn.4211200","volume-title":"Exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol S exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposure","author":"Easson","year":"2022"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3978","DOI":"10.2903\/j.efsa.2015.3978","article-title":"Scientific Opinion on the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs","volume":"13","year":"2015","journal-title":"EFSA J"},{"key":"B12","doi-asserted-by":"publisher","first-page":"15948","DOI":"10.1038\/s41598-019-52350-y","article-title":"Bisphenol S rapidly depresses heart function through estrogen receptor-\u03b2 and decreases phospholamban phosphorylation in a sex-dependent manner","volume":"9","author":"Ferguson","year":"2019","journal-title":"Sci. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1111\/j.1365-2605.2005.00563.x","article-title":"Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters","volume":"29","author":"Foster","year":"2006","journal-title":"Int. J. Androl."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e211","DOI":"10.1097\/MD.0000000000000211","article-title":"Bisphenol A and hormone-associated cancers: Current progress and perspectives","volume":"94","author":"Gao","year":"2015","journal-title":"Medicine"},{"key":"B15","doi-asserted-by":"publisher","first-page":"8399","DOI":"10.3390\/ijerph110808399","article-title":"Impact of bisphenol A on the cardiovascular system - epidemiological and experimental evidence and molecular mechanisms","volume":"11","author":"Gao","year":"2014","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B16","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1152\/ajpheart.00272.2015","article-title":"Physiological response of cardiac tissue to bisphenol a: Alterations in ventricular pressure and contractility","volume":"309","author":"Gillum Posnack","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.chemosphere.2018.12.109","article-title":"Toxicokinetics of bisphenol A, bisphenol S, and bisphenol F in a pregnancy sheep model","volume":"220","author":"Gingrich","year":"2019","journal-title":"Chemosphere"},{"key":"B18","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1002\/bdrb.20275","article-title":"Bisphenol A: Developmental toxicity from early prenatal exposure","volume":"89","author":"Golub","year":"2010","journal-title":"Birth Defects Res. B Dev. Reprod. Toxicol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.envint.2018.08.019","article-title":"Bisphenol S instead of Bisphenol A: Toxicokinetic investigations in the ovine materno-feto-placental unit","volume":"120","author":"Grandin","year":"2018","journal-title":"Environ. Int."},{"key":"B20","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1046\/j.1525-1373.2000.22402.x","article-title":"Reproductive malformation of the male offspring following maternal exposure to estrogenic chemicals","volume":"224","author":"Gupta","year":"2000","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1152\/physiolgenomics.00039.2007","article-title":"Effect of ovariectomy on cardiac gene expression: Inflammation and changes in SOCS gene expression","volume":"32","author":"Hamilton","year":"2008","journal-title":"Physiol. Genomics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1161\/01.res.87.8.677","article-title":"Membrane estrogen receptor engagement activates endothelial nitric oxide synthase via the PI3-kinase-Akt pathway in human endothelial cells","volume":"87","author":"Haynes","year":"2000","journal-title":"Circ. Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"5457","DOI":"10.1007\/s11356-014-2570-z","article-title":"Anogenital distance and its application in environmental health research","volume":"21","author":"Liu","year":"2014","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"B24","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s12902-018-0310-y","article-title":"Bisphenol A exposure and type 2 diabetes mellitus risk: A meta-analysis","volume":"18","author":"Hwang","year":"2018","journal-title":"BMC Endocr. Disord."},{"key":"B25","doi-asserted-by":"publisher","first-page":"H330","DOI":"10.1152\/ajpheart.00841.2016","article-title":"Rapid estrogen receptor-\u03b1 signaling mediated by ERK activation regulates vascular tone in male and ovary-intact female mice","volume":"314","author":"Kim","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.pharmthera.2012.03.007","article-title":"Estrogen and the cardiovascular system","volume":"135","author":"Knowlton","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"375","DOI":"10.2486\/indhealth.40.375","article-title":"Effects of in utero and lactational exposure to bisphenol A on somatic growth and anogenital distance in F1 rat offspring","volume":"40","author":"Kobayashi","year":"2002","journal-title":"Ind. Health"},{"key":"B28","doi-asserted-by":"publisher","first-page":"152234","DOI":"10.1016\/j.tox.2019.06.005","article-title":"Bisphenol S alters development of the male mouse mammary gland and sensitizes it to a peripubertal estrogen challenge","volume":"424","author":"Kolla","year":"2019","journal-title":"Toxicology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1016\/j.scitotenv.2017.10.042","article-title":"Bisphenol A distribution in serum, urine, placenta, breast milk, and umbilical cord serum in a birth panel of mother\u2013neonate pairs","volume":"626","author":"Lee","year":"2018","journal-title":"Sci. Total Environ."},{"key":"B30","doi-asserted-by":"publisher","first-page":"6860","DOI":"10.1021\/es301334j","article-title":"Bisphenol S in urine from the United States and seven Asian countries: Occurrence and human exposures","volume":"46","author":"Liao","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1161\/01.res.81.3.355","article-title":"Estrogen upregulates endothelial nitric oxide synthase gene expression in fetal pulmonary artery endothelium","volume":"81","author":"MacRitchie","year":"1997","journal-title":"Circ. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"25","DOI":"10.4274\/jcrpe.4817","article-title":"High prenatal exposure to bisphenol A reduces anogenital distance in healthy male newborns","volume":"10","author":"Mammadov","year":"2018","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.reprotox.2006.10.002","article-title":"Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure","volume":"23","author":"Murray","year":"2007","journal-title":"Reprod. Toxicol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"114036","DOI":"10.1016\/j.envpol.2020.114036","article-title":"The mixture effects of bisphenol derivatives on estrogen receptor and androgen receptor","volume":"260","author":"Park","year":"2020","journal-title":"Environ. Pollut."},{"key":"B35","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/toxsci\/kfz173","article-title":"Characterization of estrogenic and androgenic activities for bisphenol A-like chemicals (BPs): In vitro estrogen and androgen receptors transcriptional activation, gene regulation, and binding profiles","volume":"178","author":"Pelch","year":"2019","journal-title":"Toxicol. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1097\/FJC.0b013e31828bc88a","article-title":"Subtype-specific estrogen receptor-mediated vasodilator activity in the cephalic, thoracic and abdominal vasculature of female rat","volume":"62","author":"Reslan","year":"2013","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"3636","DOI":"10.1007\/s11356-018-3823-z","article-title":"Bisphenol S exposure affects gene expression related to intestinal glucose absorption and glucose metabolism in mice","volume":"26","author":"Rezg","year":"2019","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"B38","doi-asserted-by":"publisher","first-page":"E22","DOI":"10.3390\/toxics5030022","article-title":"Occupational exposure to bisphenol A (BPA): A reality that still needs to Be unveiled.","volume":"5","author":"Ribeiro","year":"2017","journal-title":"Toxics"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4190","DOI":"10.1038\/s41598-020-61014-1","article-title":"Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3\/CamKII dependent pathway","volume":"10","author":"Sanchez-esteban","year":"2020","journal-title":"Sci. Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"4719","DOI":"10.1096\/fj.14-252460","article-title":"Oral administration of bisphenol A induces high blood pressure through angiotensin II\/CaMKII-dependent uncoupling of eNOS","volume":"28","author":"Saura","year":"2014","journal-title":"FASEB J."},{"key":"B41","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s00204-018-2350-5","article-title":"Anogenital distance as a toxicological or clinical marker for fetal androgen action and risk for reproductive disorders","volume":"93","author":"Schwartz","year":"2018","journal-title":"Arch. Toxicol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1093\/toxsci\/kfz124","article-title":"Prenatal exposure to bisphenol A, E, and S induces transgenerational effects on female reproductive functions in mice","volume":"170","author":"Shi","year":"2019","journal-title":"Toxicol. Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.reprotox.2019.02.009","article-title":"Bisphenol-S promotes endocrine-disrupting effects similar to those promoted by bisphenol-A in the prostate of adult gerbils","volume":"85","author":"Silva","year":"2019","journal-title":"Reprod. Toxicol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.envint.2018.08.055","article-title":"Maternal exposure to bisphenol A and anogenital distance throughout infancy: A longitudinal study from shanghai, China","volume":"121","author":"Sun","year":"2018","journal-title":"Environ. Int."},{"key":"B45","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1093\/humrep\/deu363","article-title":"First trimester phthalate exposure and anogenital distance in newborns","volume":"30","author":"Swan","year":"2015","journal-title":"Hum. Reprod."},{"key":"B46","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1476-069X-12-26","article-title":"Mixtures of xenoestrogens disrupt estradiol-induced non-genomic signaling and downstream functions in pituitary cells","volume":"12","author":"Vi\u00f1as","year":"2013","journal-title":"Environ. Health"},{"key":"B47","doi-asserted-by":"publisher","first-page":"14737","DOI":"10.1074\/jbc.r110.191791","article-title":"Non-nuclear estrogen receptor signaling in the endothelium","volume":"286","author":"Wu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B48","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/rmb2.12006","article-title":"Molecular mechanism of estrogen\u2013estrogen receptor signaling","volume":"16","author":"Ya\u015far","year":"2017","journal-title":"Reprod. Med. Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"125805","DOI":"10.1016\/j.chemosphere.2019.125805","article-title":"Prenatal exposure to bisphenol a and its analogues (bisphenol F and S) and ultrasound parameters of fetal growth","volume":"246","author":"Zhou","year":"2020","journal-title":"Chemosphere"}],"container-title":["Frontiers in Toxicology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2022.933572\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T03:09:22Z","timestamp":1665630562000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2022.933572\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,13]]},"references-count":49,"alternative-id":["10.3389\/ftox.2022.933572"],"URL":"https:\/\/doi.org\/10.3389\/ftox.2022.933572","relation":{},"ISSN":["2673-3080"],"issn-type":[{"value":"2673-3080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,13]]},"article-number":"933572"}}