PMID- 26171567 OWN - NLM STAT- MEDLINE DCOM- 20160718 LR - 20181113 IS - 1872-9738 (Electronic) IS - 0892-0362 (Print) IS - 0892-0362 (Linking) VI - 51 DP - 2015 Sep-Oct TI - Low and moderate prenatal ethanol exposures of mice during gastrulation or neurulation delays neurobehavioral development. PG - 1-11 LID - S0892-0362(15)30012-X [pii] LID - 10.1016/j.ntt.2015.07.003 [doi] AB - Human and animal studies show significant delays in neurobehavioral development in offspring after prolonged prenatal exposure to moderate and high ethanol doses resulting in high blood alcohol concentration (BECs). However, none have investigated the effects of lower ethanol doses given acutely during specific developmental time periods. Here, we sought to create a mouse model for modest and circumscribed human drinking during the 3rd and 4th weeks of pregnancy. We acutely treated mice during embryo gastrulation on gestational day (GD) 7 or neurulation on GD8 with a low or moderate ethanol dose given via gavage that resulted in BECs of 107 and 177 mg/dl, respectively. We assessed neonatal physical development (pinnae unfolding, and eye opening); weight gain from postnatal day (PD) 3-65; and neurobehavioral maturation (pivoting, walking, cliff aversion, surface righting, vertical screen grasp, and rope balance) from PD3 to 17. We used a multiple linear regression model to determine the effects of dose, sex, day of treatment and birth in animals dosed during gastrulation or neurulation, relative to their vehicle controls. We found that ethanol exposure during both time points (GD7 and GD8) resulted in some delays of physical development and significant sensorimotor delays of pivoting, walking, and thick rope balance, as well as additional significant delays in cliff aversion and surface righting after GD8 treatment. We also found that treatment with the low ethanol dose more frequently affected neurobehavioral development of the surviving pups than treatment with the moderate ethanol dose, possibly due to a loss of severely affected offspring. Finally, mice born prematurely were delayed in their physical and sensorimotor development. Importantly, we showed that brief exposure to low dose ethanol, if administered during vulnerable periods of neuroanatomical development, results in significant neurobehavioral delays in neonatal mice. We thus expand concerns about alcohol consumption during the 3rd and 4th weeks of human pregnancy to include occasional light to moderate drinking. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Schambra, Uta B AU - Schambra UB AD - Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. Electronic address: schambra@etsu.edu. FAU - Goldsmith, Jeff AU - Goldsmith J AD - Columbia Mailman School of Public Health, Department of Biostatistics, New York, NY 10023, USA. FAU - Nunley, Kevin AU - Nunley K AD - Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. FAU - Liu, Yali AU - Liu Y AD - Department of Mathematics & Statistics, College of Arts and Sciences, East Tennessee State University, Johnson City, TN 37614, USA. FAU - Harirforoosh, Sam AU - Harirforoosh S AD - Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, USA. FAU - Schambra, Heidi M AU - Schambra HM AD - Department of Rehabilitation & Regenerative Medicine, Columbia University Medical Center, New York, NY 10032, USA. LA - eng GR - K23 NS078052/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150711 PL - United States TA - Neurotoxicol Teratol JT - Neurotoxicology and teratology JID - 8709538 RN - 0 (Central Nervous System Depressants) RN - 3K9958V90M (Ethanol) SB - IM MH - Age Factors MH - Animals MH - Animals, Newborn MH - Body Weight/drug effects MH - Central Nervous System Depressants/blood/*toxicity MH - Developmental Disabilities/*chemically induced MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Ethanol/blood/*toxicity MH - Female MH - Gastrulation/*drug effects MH - Locomotion/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Muscle Strength/drug effects MH - Neurulation/*drug effects MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*chemically induced MH - Reaction Time/drug effects MH - Sensation Disorders/chemically induced PMC - PMC4592804 MID - NIHMS710457 OTO - NOTNLM OT - Gastrulation OT - Low ethanol dose OT - Moderate ethanol dose OT - Mouse OT - Neurobehavioral delays OT - Neurulation OT - Premature birth OT - Sensorimotor development COIS- Conflict of interest statement The authors declare that there are no conflicts of interest. EDAT- 2015/07/15 06:00 MHDA- 2016/07/19 06:00 PMCR- 2016/09/01 CRDT- 2015/07/15 06:00 PHST- 2014/11/12 00:00 [received] PHST- 2015/06/28 00:00 [revised] PHST- 2015/07/05 00:00 [accepted] PHST- 2015/07/15 06:00 [entrez] PHST- 2015/07/15 06:00 [pubmed] PHST- 2016/07/19 06:00 [medline] PHST- 2016/09/01 00:00 [pmc-release] AID - S0892-0362(15)30012-X [pii] AID - 10.1016/j.ntt.2015.07.003 [doi] PST - ppublish SO - Neurotoxicol Teratol. 2015 Sep-Oct;51:1-11. doi: 10.1016/j.ntt.2015.07.003. Epub 2015 Jul 11.