Maternal and Neonatal Plasma MicroRNA Biomarkers for Fetal Alcohol Exposure in an Ovine Model

Authors

  • Sridevi Balaraman,

    1. Department of Neuroscience and Experimental Therapeutics, and Women's Health in Neuroscience Program, Texas A&M Health Science Center, College of Medicine, Bryan, Texas
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  • E. Raine Lunde,

    1. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College of Veterinary Medicine, College Station, Texas
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  • Onkar Sawant,

    1. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College of Veterinary Medicine, College Station, Texas
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  • Timothy A. Cudd,

    1. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College of Veterinary Medicine, College Station, Texas
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  • Shannon E. Washburn,

    1. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College of Veterinary Medicine, College Station, Texas
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  • Rajesh C. Miranda

    Corresponding author
    1. Department of Neuroscience and Experimental Therapeutics, and Women's Health in Neuroscience Program, Texas A&M Health Science Center, College of Medicine, Bryan, Texas
    • Reprint requests: Rajesh C. Miranda, Department of Neuroscience and Experimental Therapeutics, and Women's Health in Neuroscience Program, Texas A&M Health Science Ctr., College of Medicine, Medical Research and Education Bldg, 8447 State Highway 47, Bryan, TX 77807-3260; Tel.: 979-436-0332; Fax: 979-436-0086; E-mail: miranda@medicine.tamhsc.edu

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Abstract

Background

Plasma or circulating miRNAs (cirmiRNAs) 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 cirmiRNA profiles were similar to each other and different from nonpregnant female plasma, erythrocyte, or leukocyte miRNAs. Significant changes in cirmiRNA profiles were observed in the EtOH-exposed ewe and, at birth, in the in utero, EtOH-exposed lamb. CirmiRNAs 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 cirmiRNA ratios in the pregnant ewe, but not in the lamb.

Conclusions

Shared profiles between pregnant dam and neonate suggest possible maternal-fetal miRNA transfer. CirmiRNAs 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.

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