{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T23:31:48Z","timestamp":1768865508433,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,3,12]],"date-time":"2009-03-12T00:00:00Z","timestamp":1236816000000},"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 Pt B"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND<\/jats:bold>: Natalizumab is a humanized monoclonal immunoglobulin G4 antibody directed against the human \u03b14 integrin subunit disrupting interaction with its ligands. As \u03b14 integrins and\/or their ligands appear to be involved in reproductive function, the effects of natalizumab on fertility in male and female guinea pigs were investigated. <jats:bold>METHODS<\/jats:bold>: Natalizumab was administered by bolus intravenous injection every other day at doses of 0, 3, 10, and 30\u2009mg\/kg. Males began treatment at least 28 days prior to mating until necropsy (approximately 3 to 5 days after mating). Dosing in females was done from gestational day (GD) of an existing pregnancy to GD 30 of a second pregnancy. <jats:bold>RESULTS<\/jats:bold>: In male guinea pigs, natalizumab treatment had no effect on sperm parameters, reproductive organ weights, organ\u2010weight ratios, or histology of the testis or epididymis. Natalizumab did not affect the ability of treated males to produce pregnancies in untreated females. In female guinea pigs, no treatment\u2010related changes were seen in uterine weights or ovary weights. Pregnancy rates were reduced in females treated with 30\u2009mg\/kg natalizumab, but not those treated with 3 or 10\u2009mg\/kg. Pregnancy rates were 63.3, 66.7, 66.7, and 29.6% for groups treated with 0, 3, 10, and 30\u2009mg\/kg, respectively. Effects observed at 30\u2009mg\/kg were at exposures 36\u2010fold those observed in humans. <jats:bold>CONCLUSIONS<\/jats:bold>: Natalizumab had no effects on male fertility, but did result in a reduction in pregnancy rates in females treated with the high dose of 30\u2009mg\/kg. <jats:italic>Birth Defects Res (Part B)<\/jats:italic>86: 108\u2010116, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.20191","type":"journal-article","created":{"date-parts":[[2009,3,12]],"date-time":"2009-03-12T19:01:24Z","timestamp":1236884484000},"page":"108-116","source":"Crossref","is-referenced-by-count":34,"title":["Effects of natalizumab, an \u03b14 integrin inhibitor, on fertility in male and female guinea pigs"],"prefix":"10.1002","volume":"86","author":[{"given":"Nancy G.","family":"Wehner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Skov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Shopp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith S.","family":"Rocca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,3,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(91)90229-K"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1373.2000.22348.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/HUMREP\/10.6.1571"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1016280"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.12.3460"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2005.03.013"},{"key":"e_1_2_6_8_1","first-page":"951","article-title":"Characterization and role of integrins in mature and immature human oocytes","volume":"10","author":"de Nadai C","year":"1996","journal-title":"Mol Hum Reprod"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623308326095"},{"key":"e_1_2_6_10_1","first-page":"111","volume-title":"Handbook of developmental toxicology","author":"DeSesso JM","year":"1997"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.2307\/2528490"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod56.2.348"},{"key":"e_1_2_6_13_1","first-page":"537","article-title":"Is oncofetal fibronectin a trophoblast glue for human implantation?","volume":"138","author":"Feinberg RF","year":"1991","journal-title":"Am J Pathol"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.1080310309"},{"key":"e_1_2_6_15_1","first-page":"257","article-title":"Influence of the epididymis on integrins and matrix proteins of human spermatozoa","volume":"34","author":"Glander HJ","year":"1994","journal-title":"Acta Chir Hung"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/01485019608987094"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/14.10.2485"},{"key":"e_1_2_6_18_1","unstructured":"ICH Guideline for Industry.1994. 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