Maternal And Neonatal Plasma MicroRNA Biomarkers For Fetal Alcohol Exposure In An Ovine Model
Autor: | Shannon E. Washburn, Rajesh C. Miranda, Sridevi Balaraman, E. Raine Lunde, Timothy A. Cudd, Onkar B. Sawant |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Male
medicine.medical_specialty Erythrocytes Medicine (miscellaneous) Physiology Biology Toxicology Article Transcriptome Pregnancy Internal medicine microRNA medicine Leukocytes Endocrine system Animals reproductive and urinary physiology Sheep Ethanol medicine.disease Psychiatry and Mental health Disease Models Animal MicroRNAs Endocrinology Animals Newborn In utero Fetal Alcohol Spectrum Disorders Gestation Biomarker (medicine) Blood alcohol content Female Biomarkers |
Popis: | 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. |
Databáze: | OpenAIRE |
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