Murine embryonic stem (ES) cells constitute a versatile biological system that has facilitated major advances in the fields of cell and developmental biology. Although melatonin has a wide variety of biological functions, its effect on ES cells is still unknown. In this study, we examined the effects of melatonin on transcription factors of ES cells (ES-E14TG2a cells) using an in vitro culture system. We found that melatonin affected cellular proliferation and Akt phosphorylation. Melatonin treatment also increased Bcl-2 expression and suppressed Bax expression and decreased phosphorylation of GSK α/β. The transcription factor Oct4, which contains the POU (N-terminal to homeobox) domain, and the transcription factor Sox2, the zinc finger transcription factor Zfp206, and the zinc finger gene REX-1 (Znf42), which contain the high mobility group (HMG) domain, are all important for cellular pluripotency and pre-implantation development. In this study, melatonin treatment influenced Oct4 and REX-1 expression at day 1 but not significantly at days 2 and 3. In addition, Sox2 and Zfp206 expressions did not change over the course of melatonin treatment. Taken together, melatonin may affect Akt activation but does not influence the mRNA expressions of Oct4, REX-1, Sox2, or Zfp206, suggesting that melatonin may stimulate proliferation of ES-E14TG2a cells via Akt phosphorylation.
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