{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T23:06:03Z","timestamp":1781996763014,"version":"3.54.5"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21 ES028963"],"award-info":[{"award-number":["R21 ES028963"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32 ES007326"],"award-info":[{"award-number":["T32 ES007326"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Iodoacetic acid (IAA) is a water disinfection byproduct (DBP) formed by reactions between oxidizing disinfectants and iodide. In vitro studies have indicated that IAA is one of the most cyto- and genotoxic DBPs. In humans, DBPs have been epidemiologically associated with reproductive dysfunction. In mouse ovarian culture, IAA exposure significantly inhibits antral follicle growth and reduces estradiol production. Despite this evidence, little is known about the effects of IAA on the other components of the reproductive axis: the hypothalamus and pituitary. We tested the hypothesis that IAA disrupts expression of key neuroendocrine factors and directly induces cell damage in the mouse pituitary. We exposed adult female mice to IAA in drinking water in vivo and found 0.5 and 10\u2009mg\/l IAA concentrations lead to significantly increased mRNA levels of kisspeptin (Kiss1) in the arcuate nucleus although not affecting Kiss1 in the anteroventral periventricular nucleus. Both 10\u2009mg\/l IAA exposure in vivo and 20\u2009\u03bcM IAA in vitro reduced follicle stimulating hormone (FSH\u03b2)-positive cell number and Fshb mRNA expression. IAA did not alter luteinizing hormone (LH\u03b2) expression in vivo although exposure to 20\u2009\u03bcM IAA decreased expression of Lhb and glycoprotein hormones, alpha subunit (Cga) mRNA in vitro. IAA also had toxic effects in the pituitary, inducing DNA damage and P21\/Cdkn1a expression in vitro (20\u2009\u03bcM IAA) and DNA damage and Cdkn1a expression in vivo (500\u2009mg\/l). These data implicate IAA as a hypothalamic-pituitary-gonadal axis toxicant and suggest the pituitary is directly affected by IAA exposure.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab106","type":"journal-article","created":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T16:51:15Z","timestamp":1630169475000},"page":"46-56","source":"Crossref","is-referenced-by-count":18,"title":["Iodoacetic Acid, a Water Disinfection Byproduct, Disrupts Hypothalamic, and Pituitary Reproductive Regulatory Factors and Induces Toxicity in the Female Pituitary"],"prefix":"10.1093","volume":"184","author":[{"given":"Rachel V L","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E","family":"Weis","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andressa V","family":"Gonsioroski","sequence":"additional","affiliation":[{"name":"Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi A","family":"Flaws","sequence":"additional","affiliation":[{"name":"Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9258-4653","authenticated-orcid":false,"given":"Lori T","family":"Raetzman","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"key":"2021103112183017400_kfab106-B1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nrc2657","article-title":"P21 in cancer: Intricate networks and multiple activities","volume":"9","author":"Abbas","year":"2009","journal-title":"Nat. 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