Differentially expressed genes by DMSO in mouse 2-cell embryos identified by RNA sequencing

Since discovery of dimethyl sulfoxide (DMSO), it has been applied to the multidisciplinary studies for basic and clinic research; yet its toxicity versus biocompatibility is poorly understood, leading to our inability to discover etiology behind its paradox. Here, we found that exposure of 2% DMSO to mouse zygotes caused developmental arrest at 2/4-cell embryos, and showed a decreased total acetylation levels. Besides, H3, H4, p53, H3K9, and H3K27 acetylation levels at DMSO-exposed 2-cell embryos are significantly increased. This affected the male pronucleus more than female. Further, RNA-sequence data demonstrates that DMSO alters approximately 16.26% transcripts of 2-cell embryos. Among them, maternal and minor zygotic gene activation (ZGA) transcripts are highly increased, whereas ubiquitin-proteasome system, major ZGA, embryonic gene activation, cell cycle, and ribosomal biogenesis transcripts are significantly down-regulated. These results suggest that DMSO caused developmental arrest by disrupting maternal-to-embryonic transition due to low proteasome activity and epigenetic alternations. Overall design: We cultured 18 hours post hCG zygotes in KSOM media supplemented with or without 2% DMSO for 24 hours and then fifty of developed 2-cell embryos in each group were subjected to low-put RNA sequencing.