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Our previous studies demonstrated e-cigarettes can delay gestation. Limited studies have examined in vivo effects on the placenta.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We exposed adult pregnant C57BL\/6J female mice to flavored e-cigarettes with and without nicotine (VAPE NIC &amp; VAPE). We measured implantation success (<jats:italic>N<\/jats:italic>\u2009=\u200910 SHAM, <jats:italic>N<\/jats:italic>\u2009=\u200917 VAPE, <jats:italic>N<\/jats:italic>\u2009=\u200913 VAPE NIC), erythrocyte presence (<jats:italic>N<\/jats:italic>\u2009=\u200929 SHAM, <jats:italic>N<\/jats:italic>\u2009=\u200929 VAPE, <jats:italic>N<\/jats:italic>\u2009=\u200926 VAPE NIC) and embryo elongation (<jats:italic>N<\/jats:italic>\u2009=\u200925 SHAM, <jats:italic>N<\/jats:italic>\u2009=\u200929 VAPE, <jats:italic>N<\/jats:italic>\u2009=\u200922 VAPE NIC) per implant site at day 6.5 at 13-21 weeks of age. Fetal and placental weight (<jats:italic>N<\/jats:italic>\u2009=\u200911 SHAM, <jats:italic>N<\/jats:italic>\u2009=\u200914 VAPE, <jats:italic>N<\/jats:italic>\u2009=\u200912 VAPE NIC) was evaluated at day 12.5 in mice aged 15\u201339 weeks, while placental gene expression was separately analyzed by offspring sex (<jats:italic>N<\/jats:italic>\u2009=\u20097 total, <jats:italic>N<\/jats:italic>\u2009=\u20093 sex-specific).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Here we show that e-cigarettes cause similar embryo elongation and in the absence of nicotine, exhibit elevated implant site blood cell accumulation which may contribute to fetal demise. With nicotine, e-cigarettes elicit a reduction in embryo to placental weight ratios. Genes involved in hypoxia, reactive oxygen species response, and placental growth including hypoxia inducible factor 1, alpha subunit (<jats:italic>Hif1a<\/jats:italic>), prostaglandin-endoperoxide synthase 2 (<jats:italic>Ptgs2<\/jats:italic>), glutathione peroxidase family members 2 and 3 (<jats:italic>Gpx2<\/jats:italic>\/<jats:italic>Gpx3<\/jats:italic>), thioredoxin reductase 1 (<jats:italic>Txnrd1<\/jats:italic>), and mitogen-activated protein kinase 1 (<jats:italic>Mapk1<\/jats:italic>) exhibit marked decreases in placental tissue depending on fetal sex and nicotine presence.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our findings conclude flavored e-cigarettes modulate in vivo implantation and placentation mechanisms depending on the presence of nicotine. This work presents a measure of concern for flavored e-cigarette use during pregnancy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1038\/s43856-025-01094-0","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T08:14:16Z","timestamp":1756368856000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Flavored e-cigarettes modulate embryo development, fetal growth, and potentiate early fetal demise without nicotine"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0473-9422","authenticated-orcid":false,"given":"Margeaux W.","family":"Marbrey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel M.","family":"Cripps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rennica","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan M.","family":"Kistner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aanvi","family":"Somany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6749-7838","authenticated-orcid":false,"given":"Elizabeth S.","family":"Douglas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7033-9232","authenticated-orcid":false,"given":"Kathleen M.","family":"Caron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"1094_CR1","doi-asserted-by":"crossref","unstructured":"Kramarow, E. 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