TY - JOUR
T1 - Ethanol, acetaldehyde, and estradiol affect growth and differentiation of Rhesus monkey embryonic stem cells
AU - VandeVoort, Catherine A.
AU - Hill, Dana L.
AU - Chaffin, Charles L.
AU - Conley, Alan J
PY - 2011/8
Y1 - 2011/8
N2 - 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 4weeks. Results: Although control ESCs remained unchanged, abnormal morphology of ESCs in the ethanol and acetaldehyde treatment groups was observed before 2weeks 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.
AB - 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 4weeks. Results: Although control ESCs remained unchanged, abnormal morphology of ESCs in the ethanol and acetaldehyde treatment groups was observed before 2weeks 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.
KW - Embryo development
KW - Fetal alcohol syndrome
KW - Primate
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U2 - 10.1111/j.1530-0277.2011.01490.x
DO - 10.1111/j.1530-0277.2011.01490.x
M3 - Article
C2 - 21438889
AN - SCOPUS:79960647291
VL - 35
SP - 1534
EP - 1540
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
SN - 0145-6008
IS - 8
ER -