{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:14:02Z","timestamp":1759961642476},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,8,3]],"date-time":"2005-08-03T00:00:00Z","timestamp":1123027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2005,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Methylnitrosourea (MNU), an alkylating agent derived from creatinine metabolism, is cytotoxic, genotoxic, and mutagenic. Midgestational exposure to MNU leads to distal limb defects in mice. Previous studies have shown that nonspecific maternal immune stimulation protects against MNU\u2010induced teratogenesis. A role for immune\u2010mediated placental improvement in this effect remains uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The immune system of timed\u2010pregnant C57BL\/6N and CD\u20101 mice was stimulated by GD 7 intraperitoneal (IP) injection with the cytokine interferon\u2010\u03b3 (IFN\u2010\u03b3). A teratogenic dose of MNU was then administered by IP injection on the morning of GD 9 to disrupt distal limb formation. Fetal limb length, body length, digital deformities, and placental integrity were evaluated on GD 14.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The incidence of syndactyly, polydactyly, and interdigital webbing in MNU\u2010exposed mice was decreased by maternal IFN\u2010\u03b3 treatment. In C57BL\/6N mice, these defects were reduced by 47, 100, and 63%, respectively, as compared to previous reports on CD\u20101 mice, by 39, 71, and 20%, respectively. Administration of IFN\u2010\u03b3 significantly diminished MNU\u2010induced endothelial and trophoblast placental damage in both strains of mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>These findings support a possible link between maternal immunity, placental integrity, and fetal distal limb development. Further, these results suggest that IFN\u2010\u03b3 might act through placental improvement to indirectly protect against MNU\u2010induced fetal limb malformations. Birth Defects Research (Part A), 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20176","type":"journal-article","created":{"date-parts":[[2005,8,3]],"date-time":"2005-08-03T21:51:22Z","timestamp":1123105882000},"page":"597-604","source":"Crossref","is-referenced-by-count":7,"title":["Placental improvement and reduced distal limb defects by maternal interferon\u2010\u03b3 injection in methylnitrosourea\u2010exposed mice"],"prefix":"10.1002","volume":"73","author":[{"given":"Chelsea Lee","family":"Laudermilch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven David","family":"Holladay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan Phillip","family":"Sponenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey Kirk","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Lee","family":"Ward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Renee","family":"Prater","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,8,3]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00333418"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/80.1.154"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.05.004"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114473"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00986.x"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni846"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02441.x"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.200116116"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9926(200012)62:6<413::AID-TERA8>3.0.CO;2-B"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-5769(01)00183-7"},{"key":"e_1_2_5_12_1","article-title":"Teratogen induced birth defects in mice: role of maternal immune stimulation","author":"Hrubec TC","year":"2005","journal-title":"Curr Topics Toxicol"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8456301"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/scdb.2000.0158"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-4310(97)01011-3"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.5.1325"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00288343"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20082"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10137"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1081\/IMM-200047389"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.1108"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6866(1999)19:3<171::AID-TCM1>3.0.CO;2-S"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1530\/ror.0.0030052"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9926(200012)62:6<420::AID-TERA9>3.0.CO;2-8"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-5769(02)00094-2"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-5769(03)00093-6"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5431.1259"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0463.2001.090504.x"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2003.10.050"}],"container-title":["Birth Defects Research Part A: Clinical and Molecular Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdra.20176","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.20176","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T02:15:07Z","timestamp":1697163307000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.20176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8,3]]},"references-count":28,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2005,9]]}},"alternative-id":["10.1002\/bdra.20176"],"URL":"https:\/\/doi.org\/10.1002\/bdra.20176","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,8,3]]}}}