Effects of 17beta-estradiol and xenoestrogens on mouse embryonic stem cells.
Xenoestrogens such as 4-tert-octylphenol (OP) and 4-nonylphenol (NP) can adversely affect the reproductive and immune systems from their estrogenic effects in target cells. In this study, we investigated the effects of xenoestrogens on the expression of undifferentiation markers in mouse embryonic stem (ES) cells and of cardiomyocyte differentiation markers in mouse embryoid body (EB) cells induced to differentiate into cardiomyocytes from ES cells. The expressions of undifferentiation markers (Oct4, Sox2, Zfp206, and Rex-1) and cardiomyocyte differentiation markers (alpha-MHC, beta-MHC, ANF, and MLC-2V) were determined by semi- and quantitative real-time PCR. Treatment with E(2) or OP and NP induced an increase in Oct4 expression at the transcriptional level in a dose- and time-dependent manner. However, no difference was observed in the expression of Sox2, Zfp206 or Rex-1 genes in ES cells, suggesting that E(2) may be an Oct4 enhancer in ES cells. Induction of Oct4 expression by E(2) and xenoestrogens (OP and NP) did not change the methylation pattern of the Oct4-promoter and was not affected by treatment with a demethylating agent, 5-azacytidine. Taken together, these results suggest that E(2) and xenoestrogens may impact on the undifferentiation process of ES and EB cells, and retain ES cells in an undifferentiated state.
Jung
Eui-Man
EM
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Choi
Kyung-Chul
KC
Yu
Frank H
FH
Jeung
Eui-Bae
EB
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D004968:Estrogens, Non-Steroidal; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D004958:Estradiol; D000469:Alkaline Phosphatase; D001374:Azacitidine