DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro

         DMSO在體外誘導了人類細胞發育過程和表觀遺傳的顯著變化

     自從FDA將DMSO列為最安全的溶劑類別後，DMSO廣泛應用於生物醫學領域，特別是在低溫保存和體外實驗，包括胚胎的冷凍保存，尤其是近些年普遍應用的玻璃化冷凍。很多的胚胎冷凍液中都添加了DMSO作為冷凍保護劑，如近年口碑較好的日本加藤的玻璃化冷凍液，但是目前缺少其對胚胎的生物學效應評估，如胚胎細胞的轉錄組、蛋白質組和DNA甲基化譜研究。2019年有文獻報道，DMSO在體外誘導了人類細胞發育過程和表觀遺傳的顯著變化，部分原文和譯文如下：

       DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro

 M.Verheijen1, M. Lienhard 2, Y. Schrooders1, O. Clayton3, R. Nudischer3, S. Boerno2, B.Timmermann2, N. Selevsek4, R. Schlapbach4, H.Gmuender5, S.Gotta5, J.Geraedts6,R. Herwig2, J. Kleinjans1 & F. Caiment1

 Though clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, the FDA classifed DMSO in the safest solvent category. DMSO became widely used in many biomedical felds and biological efects were overlooked. Meanwhile, biomedical science has evolved towards sensitive high-throughput techniques and new research areas, including epigenomics and microRNAs. Considering its wide use, especially for cryopreservation and in vitro assays, we evaluated biological efect of DMSO using these technological innovations. We exposed 3D cardiac and hepatic microtissues to medium with or without 0.1% DMSO and analyzed the transcriptome, proteome and DNA methylation profles. In both tissue types, transcriptome analysis detected >2000 diferentially expressed genes afecting similar biological processes, thereby indicating consistent cross-organ actions of DMSO. Furthermore, microRNA analysis revealed large-scale deregulations of cardiac microRNAs and smaller, though still massive, efects in hepatic microtissues. Genome-wide methylation patterns also revealed tissue-specifcity. While hepatic microtissues demonstrated non signifcant changes, fndings from cardiac microtissues suggested disruption of DNA methylation mechanisms leading to genome-wide changes. The extreme changes in microRNAs and alterations in the epigenetic landscape indicate that DMSO is not inert. Its use should be reconsidered, especially for cryopreservation of embryos and oocytes, since it may impact embryonic development.

      雖然在20世紀60年代，二甲基亞碸(DMSO)的臨床試驗報告了其毒性，但後來，FDA將DMSO列為最安全的溶劑類別。DMSO在許多生物醫學領域得到了廣泛的應用，但其生物效應卻被忽視。與此同時，生物醫學科學已經朝著靈敏的高通量技術和新的研究領域發展，包括表觀基因組學和microRNAs。考慮到DMSO的廣泛應用，特別是在低溫保存和體外實驗，我們利用這些新型技術來評估DMSO的生物學效應。我們將三維心髒和肝髒組織塊暴露於含有或不含0.1% DMSO的培養基中，並分析其轉錄組、蛋白質組和DNA甲基化譜。在這兩種組織中，轉錄分析均發現了＞2000種表達不同的基因，它們影響相似的生物學過程，從而表明DMSO的在不同的器官中的作用是一致的。此外，microRNA分析揭示了心髒microRNA的大規模調節異常，DMSO對肝髒組織microRNA的影響較對心髒組織小，但仍是顯著的。全基因組甲基化模式也揭示了組織特異性。肝組織基因甲基化改變不明顯，而心髒組織DNA甲基化機製的破壞導致全基因組的變化。microRNA顯著變化和表觀遺傳的改變表明DMSO並非惰性的。應該重新考慮它的適用條件，特別是胚胎和卵母細胞的冷凍保存，因為DMSO可能影響胚胎發育。