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Title: Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3more » month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ; ; ;  [1] ;  [1]
  1. Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China)
  2. Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan (China)
  3. Division of Neurosurgery, Changhua Christian Hospital, Changhua 500, Taiwan (China)
  4. Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China)
Publication Date:
OSTI Identifier:
22416793
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 453; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADULTS; ALKALINE PHOSPHATASE; BONE MARROW; BRAIN; COMPARATIVE EVALUATIONS; DISEASES; ETHANOL; GENES; HOMEOSTASIS; HUMAN POPULATIONS; LYSINE; PARTURITION; PREGNANCY; RATS; RECEPTORS; SKELETON; STEM CELLS; TRABECULAR BONE; TRANSCRIPTION FACTORS