{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T15:06:24Z","timestamp":1767971184297,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2705205"],"award-info":[{"award-number":["2022YFC2705205"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2701101"],"award-info":[{"award-number":["2021YFC2701101"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Despite widespread human exposure to tin, its health effects remain poorly understood. This study examined the role of tin in neural tube defects (NTDs) through a case\u2013control study and animal experiments. Tin levels in maternal serum and placentas were analyzed in 200 NTD cases and 400 controls to explore potential associations. Elevated tin concentrations in maternal serum were associated with an increased risk of NTDs, with an odds ratio of 2.31 (95% CI, 1.13\u20134.75), with similar associations found for placental tin and tributyltin (TBT) exposure. In animal experiments, pregnant mice exposed to 10\u201340\u2009mg\/kg TBT exhibited a 25.5%\u201327.6% incidence of fetal NTDs. Maternal TBT exposure increased oxidative stress and apoptosis in embryonic neural tissues. Antibody microarray analysis prioritized MAPK signaling as the dominant perturbed pathway. Subsequent western blot and RT\u2010qPCR analysis convergently validated TBT\u2010induced MAPK hyperactivation. Vitamin E supplementation had antagonistic effects, reducing these harmful outcomes. These findings suggest that prenatal tin exposure is a significant risk factor for NTDs. The teratogenic effect of TBT appears to be mediated by enhanced oxidative stress, activation of MAPK signaling, and apoptosis in the developing neural tube, processes that can be mitigated by Vitamin E supplementation. Thus, tin exposure during pregnancy is associated with an increased risk of fetal NTDs, and animal models demonstrate that TBT can induce these defects through specific biological pathways. This research highlights the need for further investigation into tin exposure and its potential health impacts on fetal development.<\/jats:p>","DOI":"10.1002\/tox.24566","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T09:52:14Z","timestamp":1756806734000},"page":"141-150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Association to Mechanism: Excessive Exposure to Tin During Pregnancy May Cause Fetal Neural Tube Defects"],"prefix":"10.1002","volume":"41","author":[{"given":"Yongyan","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Reproductive and Child Health\/National Health Commission Key Laboratory of Reproductive Health Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre  Beijing China"},{"name":"Department of Obstetrics and Gynecology Center for Reproductive Medicine, Peking University Third Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingnan","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health\/National Health Commission Key Laboratory of Reproductive Health Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health\/National Health Commission Key Laboratory of Reproductive Health Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengrong","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health\/National Health Commission Key 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