{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:08:50Z","timestamp":1790777330986,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,6]],"date-time":"2006-01-06T00:00:00Z","timestamp":1136505600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold>Ethanol exposure during gastrulation and early neurulation induces apoptosis within certain embryonic cell populations, leading to craniofacial and neurological defects. There is currently little information about the initial kinetics of ethanol\u2010induced apoptosis, and interest in the ability of endogenous survival factors to moderate apoptosis is growing. Ethanol alters intracellular signaling, leading to cell death in chick embryos, suggesting that apoptosis could occur rapidly and that signaling pathways activated by survival factors might reduce apoptosis.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold>Pregnant mice were intubated with 1, 2, or 4 g\/kg ethanol on day 7.5 of embryogenesis (E7.5) 1, 3, or 6, hours before harvesting gastrulation\u2010stage embryos. Control animals received maltose\/dextran. Blood alcohol concentrations (BAC) were determined by gas chromatography. E7.5 embryos isolated from untreated dams were cultured in vitro for 1 or 3 hr with 0 or 400 mg% ethanol and 0 or 5 nM heparin\u2010binding epidermal growth factor (EGF)\u2010like growth factor (HB\u2010EGF). Apoptosis was quantified using fluorescence microscopy to detect annexin V binding and DNA fragmentation [<jats:italic>t<\/jats:italic>erminal deoxynucleotidyl transferase\u2010mediated d<jats:italic>U<\/jats:italic>TP\u2010X<jats:italic>n<\/jats:italic>ick<jats:italic>e<\/jats:italic>nd<jats:italic>l<\/jats:italic>abeling (TUNEL)] in whole\u2010mount or sectioned embryos.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>Both annexin V binding and TUNEL were elevated (<jats:italic>p<\/jats:italic>&lt;0.05) in embryos exposed in utero to 1 g\/kg ethanol for 3 hours, increasing linearly with time and ethanol concentration. Apoptosis increased (<jats:italic>p<\/jats:italic>&lt;0.05) in all germ cell layers. Mice treated with 4 g\/kg sustained BAC of 400 mg% for nearly 3 hours, significantly increasing apoptosis within the first hour. Cultured embryos exposed to 400 mg% ethanol displayed 2\u2010 to 3\u2010fold more TUNEL than vehicle\u2010treated embryos (<jats:italic>p<\/jats:italic>&lt;0.05); however, exogenous HB\u2010EGF prevented apoptosis.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold>Ethanol rapidly produced apoptosis in gastrulation\u2010stage embryos, consistent with induction by intracellular signaling. The ethanol\u2010induced apoptotic pathway was blocked by the endogenous survival factor, HB\u2010EGF. Differences in the expression of survival factors within individual embryos could be partly responsible for variations in the teratogenic effects of ethanol among offspring exposed prenatally.<\/jats:p>","DOI":"10.1111\/j.1530-0277.2006.00008.x","type":"journal-article","created":{"date-parts":[[2006,7,8]],"date-time":"2006-07-08T00:33:54Z","timestamp":1152318834000},"page":"127-134","source":"Crossref","is-referenced-by-count":32,"title":["Rapid Induction of Apoptosis in Gastrulating Mouse Embryos by Ethanol and Its Prevention by HB\u2010EGF"],"prefix":"10.1111","volume":"30","author":[{"given":"Brian A.","family":"Kilburn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po Jen","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George R.","family":"Flentke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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