Supported by NIH grants RR00169, AA014173, and AA019595.
Ethanol, Acetaldehyde, and Estradiol Affect Growth and Differentiation of Rhesus Monkey Embryonic Stem Cells
Article first published online: 25 MAR 2011
Copyright © 2011 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 35, Issue 8, pages 1534–1540, August 2011
How to Cite
VandeVoort, C. A., Hill, D. L., Chaffin, C. L. and Conley, A. J. (2011), Ethanol, Acetaldehyde, and Estradiol Affect Growth and Differentiation of Rhesus Monkey Embryonic Stem Cells. Alcoholism: Clinical and Experimental Research, 35: 1534–1540. doi: 10.1111/j.1530-0277.2011.01490.x
- Issue published online: 22 JUL 2011
- Article first published online: 25 MAR 2011
- Received for publication May 14, 2010; accepted January 6, 2011.
- Fetal Alcohol Syndrome;
- Embryo Development
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.