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The Role of Dimethyl Sulfoxide in Epigenetic Reprogramming by Mouse Preimplantation Embryos

초록

영어

Dimethyl sulfoxide (DMSO) is one of the most commonly used solvents in drug screening or for cryoprotection. In this study, we exposed mouse-derived zygote to blastocyst to three different concentrations of DMSO [0% (control), 0.5% (medium dose) and 1.0~2% (high dose)] to identify the safest dose that could effectively be used as solvent. We found that DMSO treatment substantially altered the developmental competency of mouse preimplantation embryos in concurrence with a significant reduction in embryo viability in a dose-dependent manner. Furthermore, Gene expression studies revealed a selective expression change of key markers associated with genome-wide DNA methylation reprogramming during preimplantation stages. Immunocytochemistry analysis demonstrated substantial alterations in the levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), increasing of apoptosis, and reduction of total cell numbers. Our study advocates for the first time that DMSO exposure induces significant alteration in gene expression, epigenetic reprogramming, and functionality of the preimplantation embryos. Also, the present study identified DMSO as a novel inducer of Tet1 and Tet2 expressions, and as a novel inhibitor for 5mC/5hmC conversion. Overall, our experiments warrant that mouse preimplantation-based assays can provide timely alerts about the outcome of widespread applications of DMSO as drug solvent and cryoprotectant agent.

저자정보

  • Min-Hui Kang Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University
  • DaSom Kim Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University
  • Yun-Jung Choi Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University
  • Deug-Nam Kwon Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University
  • Chankyu Park Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University
  • Ssang-Goo Cho Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University
  • Han Geuk Seo Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University
  • Sangiliyandi Gurunathan Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University
  • Jin-Hoi Kim Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University

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