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

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.