{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:22:54Z","timestamp":1791501774989,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020477","name":"Edward Via College of Osteopathic Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020477","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Quaternary ammonium compounds (QACs) are common chemicals used for their antimicrobial, antistatic, and surfactant properties. Two common QACs, alkyldimethylbenzyl ammonium chloride (ADBAC or BAC) and didecyldimethyl ammonium chloride (DDAC), cause neural tube defects (NTDs) in mice and are proinflammatory in both mice and humans. The maternal immune system plays an integral role in normal fetal development with cytokine mediators in the placenta directing both placental and fetal development. This study was conducted to determine whether maternal systemic or placental inflammation was involved in QAC\u2010induced NTDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Pregnant CD\u20101 mice received either a single gavage dose on gestational day (GD) 8.5; two gavage doses, one on GD 7.5 and the other on GD 8.5; or were dosed in the feed prior to mating and throughout breeding and gestation. Maternal whole blood, maternal bone marrow\u2010derived macrophages, placentas, GD 10.5 embryos, and GD 17.5 fetuses were collected for NTD, cytokine and QAC analysis. Cytokines IL\u20106, IL\u201010, IL\u201012, PlGF, and TNF\u2010\u03b1 were determined by ELISA. ADBAC and DDAC concentrations were determined by UPLC\u2013MS\/MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ADBAC and DDAC concentrated in placental tissue. Placentas from exposed pregnancies demonstrated increased production of inflammatory IL\u201010, IL\u20106, and TNF\u2010\u03b1 in embryo\u2013placental units with NTDs. Inflammatory IL\u201010, anti\u2010inflammatory IL\u201010, IL\u20106, and TNF\u2010\u03b1 were increased in macrophages isolated from QAC\u2010exposed mothers, and plasma IL\u20106, and TNF\u2010\u03b1 were correlated with NTDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The placenta is the target tissue for ADBAC and DDAC\u2010induced teratogenicity. Both placental inflammation and maternal systemic inflammation are likely involved in QAC\u2010induced NTD formation in mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.2539","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:42:46Z","timestamp":1762342966000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Maternal and Placental Inflammation Influence Formation of Neural Tube Defects in Quaternary Ammonium Compound Exposed Mice"],"prefix":"10.1002","volume":"117","author":[{"given":"Justin","family":"Kula","sequence":"first","affiliation":[{"name":"Edward Via College of Osteopathic Medicine Virginia Campus  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan P.","family":"Seguin","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy University of Washington  Seattle 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