Department of Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, South Korea.
Department of Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, South Korea.
Biomaterials. 2020 Feb;230:119604. doi: 10.1016/j.biomaterials.2019.119604. Epub 2019 Nov 14.
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.
二甲基亚砜（DMSO）广泛应用于基础和临床研究，但它的毒性和生物相容性特性仍不清楚。在这里，我们报告说，暴露于 2% DMSO 的小鼠胚胎扰乱了母源到胚胎转变所必需的转录程序，并在 2 细胞或 4 细胞阶段引发发育停滞。从机制上讲，DMSO 降低了 2 细胞胚胎中的总蛋白乙酰化水平，但增加了组蛋白 H3 和 H4 的乙酰化，以及 p53、H3K9 和 H3K27 的乙酰化。这些表观遗传变化导致暴露于 DMSO 的胚胎中总有效基因的 16.26%的表达模式发生改变。在受影响的基因中，母源和少量合子基因激活（ZGA）基因的表达增强，而泛素-蛋白酶体系统、主要 ZGA 转录物、胚胎基因激活、细胞周期和核糖体生物发生基因受到抑制。因此，我们得出结论，DMSO 通过扰乱母源到胚胎的转变而导致发育停滞；因此，在将其用作溶剂时应谨慎使用。
