Exposure of mouse oocytes to N,N‐dimethylformamide impairs mitochondrial functions and reduces oocyte quality

Abstract

N,N-dimethylformamide (DMF) is a widely-used solvent for the synthesis of synthetic fibers such as polyacrylonitrile fiber, and can also be used to make medicine.Although this organic solvent has multipurpose applications, its biological toxicity cannot be ignored and its impact on mammalian reproduction remains largely unexplored. Our study found that DMF exposure inhibited oocyte maturation and fertilization ability. Transcriptomic analysis indicated that DMF exposure changed the expression of genes and transposable elements in oocytes. Subcellular structure examination found that DMF exposure caused mitochondrial dysfunction, abnormal aggregation of mitochondria and decreased mitochondrial membrane potential in mouse oocytes. Its exposure also caused abnormal distribution of Golgi apparatus and endoplasmic reticulum which formed large number of clusters. In addition, oxidative stress occurs in oocytes exposed to DMF, which was manifested by an increase in the level of reactive oxygen species. We found that DMF exposure induced disordered spindle and chromosomes abnormality. Meanwhile, we examined various histone modification levels in oocytes exposed to DMF and found that DMF exposure reduced H3K9me3, H3K9ac, H3K27ac, and H4K16ac levels in mouse oocytes. Moreover, DMF-treated oocytes failed to form pronuclei after fusion with normal sperm.Collectively, DMF exposure caused mitochondrial damage, oxidative stress, spindle assembly and chromosome arrangement disorder, leading to oocyte maturation arrest and fertilization failure.

Improved 2-pyridyl reductive homocoupling reaction using biorenewable solvent Cyrene™ (dihydrolevoglucosenone)

“…For details see the standard analytical procedure. Cyrene™ was by far the best solvent for this reaction with a conversion of 98% aer 24 h. DMF, which has shown to be a reproductive toxin, 25 resulted in a slow reaction achieving 53% in that same time period. Similar conversions were observed with ACN, which is not considered a green solvent, and GVL.…”

Real-time breath metabolomics to assess early response to CFTR modulators in adults with cystic fibrosis: an open-label proof-of-concept study

“…Woollam et al also observed a downregulation of longer aldehydes (octanal and nonanal) in patients treated with CFTR modulators [30]. Another significant VOC, dimethylformamide has been recently associated with dysfunctions in mitochondria [34] and glucose metabolism [35]. Given ETI is suspected to affect mitochondrial function [36], a decrease in dimethylformamide ( p =0.005) towards the healthy level may parallel a shift, or even a normalisation, in energy metabolism upon ETI treatment.…”

Characterization of MicroRNAs Associated with Reproduction in the Brown Planthopper, Nilaparvata lugens

“…Furthermore, mitochondrial failure enhanced ROS generation, whereas excessive ROS caused oxidative stress, which hampered the maturation of oocytes [ 44 ]. The GO enrichment results indicate that the target genes of these DEMs may play a crucial role in oocyte development by regulating various physiological activities.…”