Ethanol, Acetaldehyde, and Estradiol Affect Growth and Differentiation of Rhesus Monkey Embryonic Stem Cells

California National Primate Research Center, Davis, CA 95616, USA.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 03/2011; 35(8):1534-40. DOI: 10.1111/j.1530-0277.2011.01490.x
Source: PubMed


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.
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.
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.
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.

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    • "Rhesus monkey ESCs (rESCs) have become an important tool used in molecular biology research. They can be used to explore complicated disease mechanisms in vitro [25, 26] and can also be used in transplantation studies to model diseases in situ [3]. One of the great advantages of rhesus monkey ESCs is that they share many characteristics with human ESCs, including cellular morphology, surface marker expression, and developmental potential [10], as well as greater than 90% DNA homology [27–30], which allows for better mimicry of the human system. "
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