title: Maternal and neonatal plasma microRNA biomarkers for fetal alcohol exposure in an ovine model.
abstract: BACKGROUND
  Plasma or circulating miRNAs (cir miRNAs) have potential diagnostic value as biomarkers for a range of diseases. Based on observations that ethanol (EtOH) altered intracellular miRNAs during development, we tested the hypothesis that plasma miRNAs were biomarkers for maternal alcohol exposure, and for past in utero exposure, in the neonate.
  
  
  METHODS
  Pregnant sheep were exposed to a binge model of EtOH consumption resulting in an average peak blood alcohol content of 243 mg/dl, for a third-trimester-equivalent period from gestational day 4 (GD4) to GD132. MiRNA profiles were assessed by quantitative PCR analysis in plasma, erythrocyte, and leukocytes obtained from nonpregnant ewes, and plasma from pregnant ewes 24 hours following the last binge EtOH episode, and from newborn lambs, at birth on ~GD147.
  
  
  RESULTS
  Pregnant ewe and newborn lamb cir miRNA profiles were similar to each other and different from nonpregnant female plasma, erythrocyte, or leukocyte miRNAs. Significant changes in cir miRNA profiles were observed in the EtOH-exposed ewe and, at birth, in the in utero, EtOH-exposed lamb. Cir miRNAs including miR-9, -15b, -19b, and -20a were sensitive and specific measures of EtOH exposure in both pregnant ewe and newborn lamb. Additionally, EtOH exposure altered guide-to-passenger strand cir miRNA ratios in the pregnant ewe, but not in the lamb.
  
  
  CONCLUSIONS
  Shared profiles between pregnant dam and neonate suggest possible maternal-fetal miRNA transfer. Cir miRNAs are biomarkers for alcohol exposure during pregnancy, in both mother and neonate, and may constitute an important shared endocrine biomarker that is vulnerable to the maternal environment.
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, and Women's Health in Neuroscience Program, Texas A&M Health Science Center, College of Medicine, Bryan, Texas.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Balaraman
authors.forename: E Raine
authors.initials: ER
authors.lastname: Lunde
authors.forename: Onkar
authors.initials: O
authors.lastname: Sawant
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Cudd
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Washburn
authors.forename: Rajesh C
authors.initials: RC
authors.lastname: Miranda
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000737:chemistry; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000097:blood* / Q000175:diagnosis; D007962:Leukocytes / Q000737:chemistry; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D011247:Pregnancy / Q000097:blood / Q000187:drug effects; D012756:Sheep; D059467:Transcriptome / Q000187:drug effects
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D000431:Ethanol
keywords: Fetal Alcohol Exposure; Maternal Alcohol Exposure; Passenger Strand miRNA; Plasma miRNAs; miRNA*