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Title: Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

Abstract

Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryomore » at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this stage is so vulnerable to the development of neural tube defect, and growth restriction, the findings previously observed in fetal alcohol syndrome.« less

Authors:
 [1];  [2];  [3];  [2]; ;  [1];  [2]
  1. Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland)
  2. (Finland)
  3. Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Kuopio (Finland)
Publication Date:
OSTI Identifier:
22416336
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 446; Journal Issue: 1; 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; ANIMAL TISSUES; BLOOD VESSELS; CELL PROLIFERATION; CONCENTRATION RATIO; DNA; EMBRYOS; ETHANOL; HOMEOSTASIS; INTRAPERITONEAL INJECTION; METABOLISM; MICE; PLACENTA; PROTEINS; PUTRESCINE; RNA; SPROUTING; SYNTHESIS; UPTAKE

Citation Formats

Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi, Medical Research Center, Oulu University Hospital, Oulu, Alhonen, Leena, School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio, Salonurmi, Tuire, Savolainen, Markku J., and Medical Research Center, Oulu University Hospital, Oulu. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.02.079.
Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi, Medical Research Center, Oulu University Hospital, Oulu, Alhonen, Leena, School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio, Salonurmi, Tuire, Savolainen, Markku J., & Medical Research Center, Oulu University Hospital, Oulu. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome. United States. doi:10.1016/J.BBRC.2014.02.079.
Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi, Medical Research Center, Oulu University Hospital, Oulu, Alhonen, Leena, School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio, Salonurmi, Tuire, Savolainen, Markku J., and Medical Research Center, Oulu University Hospital, Oulu. Fri . "Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome". United States. doi:10.1016/J.BBRC.2014.02.079.
@article{osti_22416336,
title = {Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome},
author = {Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi and Medical Research Center, Oulu University Hospital, Oulu and Alhonen, Leena and School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio and Salonurmi, Tuire and Savolainen, Markku J. and Medical Research Center, Oulu University Hospital, Oulu},
abstractNote = {Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this stage is so vulnerable to the development of neural tube defect, and growth restriction, the findings previously observed in fetal alcohol syndrome.},
doi = {10.1016/J.BBRC.2014.02.079},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 446,
place = {United States},
year = {Fri Mar 28 00:00:00 EDT 2014},
month = {Fri Mar 28 00:00:00 EDT 2014}
}
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