{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:09:17Z","timestamp":1763035757069,"version":"3.37.3"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,4,14]],"date-time":"2003-04-14T00:00:00Z","timestamp":1050278400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001786","name":"The University of Adelaide","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001786","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2003,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>During pregnancy, exposure to lipopolysaccharide (LPS) can lead to abortion, preterm delivery, and teratogenicity. The mechanisms underlying these effects are unclear. Both LPS and ethanol are potent inducers of liver metallothionein (MT), a key Zn binding protein. The teratogenic effects of ethanol have been linked to MT\u2010induced changes in maternal\u2010fetal Zn homeostasis, leading to fetal deficiency. This study was designed to assess whether the teratogenic effects of LPS are also related to MT induction and changes in Zn homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Non\u2010pregnant normal (MT+\/+) and MT\u2010null (MT\u2212\/\u2212) mice were injected subcutaneously with 0.5 \u03bcg\/gm LPS and killed over 48 hr. In MT+\/+ mice, liver MT concentrations were elevated from 6 hr, and were maximal at 24 hr (30\u2010fold basal), whereas liver Zn levels were also increased from 6 hr. Plasma Zn concentrations decreased by 80% at 6 hr, and were below normal between 6 and 24 hr. In MT\u2212\/\u2212 mice, plasma Zn levels were increased from basal between 6 and 16 hr. Dams were injected with LPS, saline, or LPS and ZnSO<jats:sub>4<\/jats:sub> (2 \u03bcg\/gm, MT+\/+ only) on Day 8 of gestation (GD8), killed on GD18, and the fetuses examined for malformations.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>External abnormalities were most prevalent in fetuses from MT+\/+ dams exposed to LPS, where 34% of fetuses in each litter were affected. MT+\/+ dams treated with LPS and ZnSO<jats:sub>4<\/jats:sub>, and MT\u2212\/\u2212 dams treated with LPS had litters in which 5.4 and 4.8% of fetuses were abnormal respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The findings of this study strongly support the hypothesis that LPS teratogenicity is mediated at least in part by MT\u2010induced changes in maternal Zn homeostasis, which compromises fetal Zn supply. Birth Defects Research (Part A) 67:240\u2013245, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.10035","type":"journal-article","created":{"date-parts":[[2003,4,16]],"date-time":"2003-04-16T10:44:14Z","timestamp":1050489854000},"page":"240-245","source":"Crossref","is-referenced-by-count":38,"title":["Zinc treatment prevents lipopolysaccharide\u2010induced teratogenicity in mice"],"prefix":"10.1002","volume":"67","author":[{"given":"Luke C.","family":"Carey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulien L.","family":"Berb\u00e9e","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Coyle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey 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