{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T14:20:55Z","timestamp":1773066055528,"version":"3.50.1"},"reference-count":73,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T00:00:00Z","timestamp":1663372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["ID2007896"],"award-info":[{"award-number":["ID2007896"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["ID1135886"],"award-info":[{"award-number":["ID1135886"]}],"id":[{"id":"10.13039\/501100000925","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":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nicotinamide adenine dinucleotide (NAD+) depletion is associated with numerous diseases in humans. Recently it was revealed that genetic blockage of the NAD+ synthesis pathway in humans causes birth defects in multiple organ systems and miscarriage. Additionally, mice with NAD+ deficiency created through dietary restriction of tryptophan and vitamin B3 were shown to have congenital anomalies affecting virtually every organ system along with miscarriage. Perturbations in NAD+\/NADH affect mechanisms of teratogenesis presented by Wilson and others, including genetic alterations, altered energy sources, and lack of precursors and substrates needed for biosynthesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Medical literature was evaluated to demonstrate how perturbations in NAD+\/NADH affect mechanisms of teratogenesis. In addition, literature describing several different teratogens of various types (infectious, physical, maternal health factors, drugs) was reviewed showing the impact of these teratogens on NAD+ and NAD+\/NADH ratios.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Many teratogens affect NAD+ by altering its metabolism, decreasing its intracellular availability, or decreasing its production, which in turn is a plausible mechanism for the creation of birth defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Looking at teratogens through the lens of their impact on NAD+ could provide valuable insight into the mechanism by which some teratogens cause birth defects and miscarriage.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2089","type":"journal-article","created":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T09:40:05Z","timestamp":1663407605000},"page":"1313-1323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Viewing teratogens through the lens of nicotinamide adenine dinucleotide (<scp>NAD<\/scp>+)"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1020-888X","authenticated-orcid":false,"given":"Paul R.","family":"Mark","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics Helen DeVos Children's Hospital, Spectrum Health  Grand Rapids Michigan USA"},{"name":"Department of Pediatrics and Human Development College of Human Medicine, Michigan State University  Grand Rapids Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2069-7349","authenticated-orcid":false,"given":"Sally L.","family":"Dunwoodie","sequence":"additional","affiliation":[{"name":"Developmental and Regenerative Biology Division Victor Chang Cardiac Research Institute  Sydney New South Wales Australia"},{"name":"School of Clinical Medicine Faculty of Medicine and Health  Sydney New South Wales Australia"},{"name":"Faculty of Science University of New South Wales  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61847"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1834"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002981"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agu010"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2002.10719191"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2307\/3576299"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9091950"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0301-472x(03)00083-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000345205"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1743"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9391261"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1161"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1916588117"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2020.07.002"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.115219"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13303"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j2249"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.139.3550.110"},{"key":"e_1_2_8_20_1","volume-title":"Understanding genetics: A District of Columbia guide for patients and health professionals","author":"Genetic Alliance; District of Columbia Department of Health","year":"2010"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00495-12"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1696"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1404269111"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.015138"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/35077232"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1630"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1011-1344(01)00211-1"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.2307\/3576192"},{"key":"e_1_2_8_29_1","first-page":"4233","article-title":"Mechanism of alteration of poly (adenosine diphosphate\u2010ribose) metabolism by hyperthermia","volume":"48","author":"Jonsson G. 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