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

Area of Science:

• Biomedical Science
• Molecular Biology
• Toxicology

Background:

• Dimethyl sulfoxide (DMSO) is widely used in biomedical applications, including cryopreservation and in vitro assays.
• Despite historical FDA classification as a safe solvent, potential biological effects of DMSO have been largely overlooked.
• Advancements in high-throughput techniques necessitate re-evaluation of DMSO's biological impact.

Purpose of the Study:

• To evaluate the biological effects of DMSO on cardiac and hepatic microtissues using transcriptomic, proteomic, and DNA methylation profiling.
• To assess DMSO's impact on microRNA expression and epigenetic modifications in different tissue types.
• To determine if DMSO's biological effects are consistent across different organs and if they warrant reconsideration of its use.

Main Methods:

• Exposure of 3D cardiac and hepatic microtissues to 0.1% DMSO.
• Analysis of transcriptome, proteome, and DNA methylation profiles.
• MicroRNA expression profiling.

Main Results:

• Transcriptome analysis revealed over 2000 differentially expressed genes in both tissue types, indicating consistent cross-organ effects of DMSO.
• MicroRNA analysis showed large-scale deregulation in cardiac microtissues and significant effects in hepatic microtissues.
• DNA methylation analysis indicated tissue-specific changes, with cardiac microtissues showing disruption of methylation mechanisms.

Conclusions:

• Dimethyl sulfoxide (DMSO) is not biologically inert and induces significant molecular and epigenetic changes.
• The observed alterations in microRNAs and DNA methylation suggest potential impacts on biological processes, including embryonic development.
• Reconsideration of DMSO's use, especially in cryopreservation of gametes and embryos, is recommended due to its non-inert biological effects.