Abstract

Though clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, the FDA classified DMSO in the safest solvent category. DMSO became widely used in many biomedical fields and biological effects 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 effect 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 profiles. In both tissue types, transcriptome analysis detected >2000 differentially expressed genes affecting 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, effects in hepatic microtissues. Genome-wide methylation patterns also revealed tissue-specificity. While hepatic microtissues demonstrated non-significant changes, findings 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.

Details

Title
DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro
Author
Verheijen, M 1 ; Lienhard, M 2   VIAFID ORCID Logo  ; Schrooders, Y 1 ; Clayton, O 3 ; Nudischer, R 3 ; Boerno, S 2 ; Timmermann, B 2 ; Selevsek, N 4 ; Schlapbach, R 4 ; Gmuender, H 5 ; Gotta, S 5 ; Geraedts, J 6 ; Herwig, R 2 ; Kleinjans, J 1 ; Caiment, F 1 

 Toxicogenomics, Maastricht University, Maastricht, Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099) 
 Max-Planck-Institute for Molecular Genetics, Computational Molecular Biology, Berlin, Germany (GRID:grid.419538.2) (ISNI:0000 0000 9071 0620) 
 F. Hoffmann-La Roche AG, Basel, Switzerland (GRID:grid.417570.0) (ISNI:0000 0004 0374 1269) 
 ETH Zurich and University of Zurich, Functional Genomics Center Zurich, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650) 
 Genedata AG, Basel, Switzerland (GRID:grid.424959.7) (ISNI:0000 0004 0509 013X) 
 Maastricht University, Medical Center, Genetics and Cell Biology, Maastricht, Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2191832644
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.