{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:45:48Z","timestamp":1740138348685,"version":"3.37.3"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T00:00:00Z","timestamp":1511308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD071408","HL128628"],"award-info":[{"award-number":["HD071408","HL128628"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007746","name":"W.K. Kellogg Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007746","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Maternal alcohol abuse leading to fetal alcohol spectrum disorder (<jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content>) includes fetal growth restriction (<jats:styled-content style=\"fixed-case\">FGR<\/jats:styled-content>). Ethanol (EtOH) induces apoptosis of human placental trophoblast cells, possibly disrupting placentation and contributing to <jats:styled-content style=\"fixed-case\">FGR<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content>. EtOH facilitates apoptosis in several embryonic tissues, including human trophoblasts, by raising intracellular Ca<jats:sup>2+<\/jats:sup>. We previously found that acute EtOH exposure increases trophoblast apoptosis due to signaling from both intracellular and extracellular Ca<jats:sup>2+<\/jats:sup>. Therefore, nifedipine, a Ca<jats:sup>2+<\/jats:sup> channel blocker that is commonly administered to treat preeclampsia and preterm labor, was evaluated for cytoprotective properties in trophoblast cells exposed to alcohol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human first\u2010trimester chorionic villous explants and the human trophoblast cell line <jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>\u20108\/<jats:styled-content style=\"fixed-case\">SV<\/jats:styled-content>neo (HTR) were pretreated with 12.5 to 50\u00a0<jats:styled-content style=\"fixed-case\">nM<\/jats:styled-content> of the Ca<jats:sup>2+<\/jats:sup> channel blocker nifedipine for 1\u00a0hour before exposure to 50\u00a0<jats:styled-content style=\"fixed-case\">mM<\/jats:styled-content> EtOH for an additional hour. Intracellular Ca<jats:sup>2+<\/jats:sup> concentrations were monitored in real time by epifluorescence microscopy, using fluo\u20104\u2010<jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content>. Apoptosis was assessed by <jats:italic>t<\/jats:italic>erminal deoxynucleotidyl transferase <jats:styled-content style=\"fixed-case\">d<jats:italic>U<\/jats:italic>TP <\/jats:styled-content><jats:italic>n<\/jats:italic>ick <jats:italic>e<\/jats:italic>nd <jats:italic>l<\/jats:italic>abeling (<jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content>), accumulation of cytoplasmic cytochrome <jats:italic>c<\/jats:italic>, and cleavage rates of caspase 3 and caspase 9.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The increase in intracellular Ca<jats:sup>2+<\/jats:sup> upon exposure to EtOH in both villous explants and <jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content> cells was completely blocked (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) when pretreated with nifedipine, accompanied by inhibition of EtOH\u2010induced release of cytochrome <jats:italic>c<\/jats:italic>, caspase activities, and <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study indicates that nifedipine can interrupt the apoptotic pathway downstream of EtOH exposure and could provide a novel strategy for future interventions in women with fetuses at risk for <jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13534","type":"journal-article","created":{"date-parts":[[2017,10,19]],"date-time":"2017-10-19T12:56:38Z","timestamp":1508417798000},"page":"53-60","source":"Crossref","is-referenced-by-count":3,"title":["Nifedipine Prevents Apoptosis of Alcohol\u2010Exposed First\u2010Trimester Trophoblast Cells"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3850-543X","authenticated-orcid":false,"given":"Alan D.","family":"Bolnick","sequence":"first","affiliation":[{"name":"Departments of Obstetrics &amp; Gynecology Wayne State University School of Medicine Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay M.","family":"Bolnick","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics &amp; Gynecology Wayne State University School of Medicine Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid\u2010Reza","family":"Kohan\u2010Ghadr","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics &amp; Gynecology Wayne State University School of Medicine Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian A.","family":"Kilburn","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics &amp; Gynecology Wayne State University School of Medicine Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hertz","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics &amp; Gynecology Wayne State University School of Medicine Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Dai","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics &amp; Gynecology Wayne State University School of Medicine Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Drewlo","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics &amp; Gynecology Wayne State University School of Medicine Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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