title: Ethanol, acetaldehyde, and estradiol affect growth and differentiation of rhesus monkey embryonic stem cells.
abstract: BACKGROUND
  The timing of the origins of fetal alcohol syndrome has been difficult to determine, in part because of the challenge associated with in vivo studies of the peri-implantation stage of embryonic development. Because embryonic stem cells (ESCs) are derived from blastocyst stage embryos, they are used as a model for early embryo development.
  
  
  METHODS
  Rhesus monkey ESC lines (ORMES-6 and ORMES-7) were treated with 0, 0.01, 0.1, or 1.0% ethanol, 1.0% ethanol with estradiol, or 0.00025% acetaldehyde with or without estradiol for 4 weeks.
  
  
  RESULTS
  Although control ESCs remained unchanged, abnormal morphology of ESCs in the ethanol and acetaldehyde treatment groups was observed before 2 weeks of treatment. Immunofluorescence staining of key pluripotency markers (TRA-1-81 and alkaline phosphatase) indicated a loss of ESC pluripotency in the 1.0% ethanol group. ORMES-7 was more sensitive to effects of ethanol than ORMES-6.
  
  
  CONCLUSIONS
  Estradiol appeared to increase sensitivity to ethanol in the ORMES-6 and ORMES-7 cell line. The morphological changes and labeling for pluripotency, proliferation, and apoptosis demonstrated that how ethanol affects these early cells that develop in culture, their differentiation state in particular. The effects of ethanol may be mediated in part through metabolic pathways regulating acetaldehyde formation, and while potentially accentuated by estradiol in some individuals, how remains to be determined.
authors: California National Primate Research Center, Davis, CA 95616, USA. cavandevoort@ucdavis.edu
authors: Catherine A
authors: CA
authors: VandeVoort
authors: Dana L
authors: DL
authors: Hill
authors: Charles L
authors: CL
authors: Chaffin
authors: Alan J
authors: AJ
authors: Conley
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001755:Blastocyst / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000378:metabolism / Q000633:toxicity*; D035061:Control Groups; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004958:Estradiol / Q000378:metabolism / Q000633:toxicity*; D004967:Estrogens / Q000378:metabolism / Q000633:toxicity*; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D008253:Macaca mulatta
chemical_list: D002492:Central Nervous System Depressants; D004967:Estrogens; D000431:Ethanol; D004958:Estradiol; D000079:Acetaldehyde