PMID- 24931007 OWN - NLM STAT- MEDLINE DCOM- 20150414 LR - 20240321 IS - 1530-0277 (Electronic) IS - 0145-6008 (Print) IS - 0145-6008 (Linking) VI - 38 IP - 7 DP - 2014 Jul TI - Dysmorphogenic effects of first trimester-equivalent ethanol exposure in mice: a magnetic resonance microscopy-based study. PG - 2008-14 LID - 10.1111/acer.12464 [doi] AB - BACKGROUND: The first trimester of human development and the equivalent developmental period in animal models is a time when teratogenic ethanol (EtOH) exposure induces the major structural birth defects that fall within fetal alcohol spectrum disorder (FASD). Previous FASD research employing an acute high dose maternal intraperitoneal EtOH treatment paradigm has identified sensitive periods for a number of these defects. Extending this work, this investigation utilized high resolution magnetic resonance microscopy (MRM)-based analyses to examine the dysmorphology resulting from maternal dietary EtOH intake occurring during selected first trimester-equivalent time periods. METHODS: Female C57Bl/6J mice were acclimated to a liquid 4.8% EtOH (v/v)-containing diet, then bred while on standard chow. Dams were again provided the EtOH-containing liquid diet for a period that extended either from the beginning of gestational day (GD) 7 to the end of GD 11 or from the beginning of GD 12 to the end of GD 16. On GD 17, a subset of fetuses was selected for MRM-based analyses. Group comparisons were made for litter characteristics and gross dysmorphology, as well as whole and regional brain volumes. RESULTS: EtOH-induced stage of exposure-dependent structural brain abnormalities were observed. The GD 7 to 11 EtOH-exposed group presented with a significant decrease in cerebellar volume and an increase in septal volume, while GD 12 to 16 EtOH treatment resulted in a reduction in right hippocampal volume accompanied by enlarged pituitaries. Additionally, the GD 12 to 16 EtOH exposure caused a high incidence of edema/fetal hydrops. CONCLUSIONS: These results illustrate the teratogenic impact of maternal dietary EtOH intake occurring at time periods approximately equivalent to weeks 3 through 6 (GD 7 to 11 in mice) and weeks 7 through 12 (GD 12 to 16 in mice) of human gestation, further documenting EtOH's stage of exposure-dependent neuroteratogenic end points and highlighting the vulnerability of selected brain regions during the first trimester. Additionally they suggest that clinical attention should be paid to fetal hydrops as a likely component of FASD. CI - Copyright (c) 2014 by the Research Society on Alcoholism. FAU - Parnell, Scott E AU - Parnell SE AD - Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, North Carolina; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, North Carolina. FAU - Holloway, Hunter E AU - Holloway HE FAU - Baker, Lorinda K AU - Baker LK FAU - Styner, Martin A AU - Styner MA FAU - Sulik, Kathleen K AU - Sulik KK LA - eng GR - P41 EB015897/EB/NIBIB NIH HHS/United States GR - P30-HD03110/HD/NICHD NIH HHS/United States GR - U54 HD079124/HD/NICHD NIH HHS/United States GR - P30 HD003110/HD/NICHD NIH HHS/United States GR - U01-AA021651/AA/NIAAA NIH HHS/United States GR - K99 AA018697/AA/NIAAA NIH HHS/United States GR - K99/R00-AA018697/AA/NIAAA NIH HHS/United States GR - P60-AA011605/AA/NIAAA NIH HHS/United States GR - U01-AA017124/AA/NIAAA NIH HHS/United States GR - P60 AA011605/AA/NIAAA NIH HHS/United States GR - U54 EB005149/EB/NIBIB NIH HHS/United States GR - P41-EB015897/EB/NIBIB NIH HHS/United States GR - U01 AA017124/AA/NIAAA NIH HHS/United States GR - U01 AA021651/AA/NIAAA NIH HHS/United States GR - U54-EB005149-01/EB/NIBIB NIH HHS/United States GR - R00 AA018697/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140613 PL - England TA - Alcohol Clin Exp Res JT - Alcoholism, clinical and experimental research JID - 7707242 RN - 3K9958V90M (Ethanol) SB - IM MH - Abnormalities, Drug-Induced/diagnosis/*pathology MH - Animals MH - Brain/*abnormalities/*drug effects MH - Ethanol/*toxicity MH - Female MH - Hydrops Fetalis/chemically induced/pathology MH - Magnetic Resonance Imaging MH - Male MH - Mice MH - Neuroimaging MH - Pituitary Gland/abnormalities MH - Pregnancy MH - *Pregnancy Trimester, First/drug effects PMC - PMC4107075 MID - NIHMS586695 OTO - NOTNLM OT - Brain OT - Ethanol OT - Fetal Alcohol Spectrum Disorder OT - Magnetic Resonance Microscopy OT - Mouse EDAT- 2014/06/17 06:00 MHDA- 2015/04/15 06:00 PMCR- 2015/07/01 CRDT- 2014/06/17 06:00 PHST- 2013/12/16 00:00 [received] PHST- 2014/04/09 00:00 [accepted] PHST- 2014/06/17 06:00 [entrez] PHST- 2014/06/17 06:00 [pubmed] PHST- 2015/04/15 06:00 [medline] PHST- 2015/07/01 00:00 [pmc-release] AID - 10.1111/acer.12464 [doi] PST - ppublish SO - Alcohol Clin Exp Res. 2014 Jul;38(7):2008-14. doi: 10.1111/acer.12464. Epub 2014 Jun 13.