DMSO impairs the transcriptional program for maternal-to-embryonic transition by altering histone acetylation

• Published in: Biomaterials Vol. 230; p. 119604
• Main Authors: Kang, Min-Hee, You, Seong-Yeob, Hong, Kwonho, Kim, Jin-Hoi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2020
• Subjects: 2-cell block; Acetylation; Animals; Dimethyl Sulfoxide - metabolism; Dimethyl Sulfoxide - toxicity; DMSO; Embryonic Development - genetics; Epigenetics; Gene Expression Regulation, Developmental; Histones - metabolism; Mice; Mouse preimplantation embryo; RNA-Seq; Zygote - metabolism; Epigenetics; Mouse preimplantation embryo; Acetylation; DMSO; RNA-Seq; 2-cell block
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2019.119604

Dimethyl sulfoxide (DMSO) is widely used in basic and clinical research, yet its toxicity and biocompatibility properties remain elusive. Here, we report that exposure of mouse zygotes to 2% DMSO perturbed the transcriptional program, critical for maternal-to-embryonic transition and provoked developmental arrest at the 2- or 4-cell stage. Mechanistically, DMSO decreased total protein acetylation in the 2-cell embryos but increased histone H3 and H4 acetylations, as well as p53, H3K9, and H3K27 acetylations. The epigenetic changes led to an altered expression pattern of 16.26% of total valid genes in DMSO-exposed embryos. Among the affected genes, expression of maternal and minor zygotic gene activation (ZGA) genes was enhanced, whereas the ubiquitin-proteasome system, major ZGA transcripts, embryonic gene activation, the cell cycle, and ribosomal biogenesis genes were suppressed. Therefore, we conclude that DMSO causes developmental arrest by disrupting maternal-to-embryonic transition; hence, caution should be exerted when using it as a solvent.