title: Ethanol-induced impairment of polyamine homeostasis--a potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu, Finland; Medical Research Center, Oulu University Hospital, Oulu, Finland. Electronic address: saeid.haghighi@oulu.fi.
authors.forename: Saeid
authors.initials: S
authors.lastname: Haghighi Poodeh
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Kuopio, Finland; School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Alhonen
authors.affiliation: Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu, Finland; Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Tuire
authors.initials: T
authors.lastname: Salonurmi
authors.affiliation: Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu, Finland; Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Savolainen
mesh_terms: D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism*; D004195:Disease Models, Animal; D047108:Embryonic Development / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D005865:Gestational Age; D006257:Head; D006706:Homeostasis / Q000187:drug effects; D051379:Mice; D009436:Neural Tube Defects / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D010641:Phenotype; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014018:Tissue Distribution; D015017:Yolk Sac / Q000187:drug effects / Q000378:metabolism
chemical_list: D015317:Biogenic Polyamines; D000431:Ethanol
keywords: Ethanol; Growth restriction; Microvascular sprouting; Neural tube defect; PECAM; Polyamine