Abstract
Methylglyoxal, a reactive dicarbonyl compound, is mainly formed from glycolysis. Methylglyoxal can lead to the dysfunction of mitochondria, the depletion of cellular anti-oxidation enzymes and the formation of advanced glycation ends. Previous studies showed that the accumulation of methylglyoxal and advanced glycation ends can impair the oocyte maturation and reduce the oocyte quality in aged and diabetic females. In this study, we showed that resveratrol, a kind of phytoalexin found in the skin of grapes, red wine and other botanical extracts, can alleviate the adverse effects caused by methylglyoxal, such as inhibition of oocyte maturation and disruption of spindle assembly. Besides, methylglyoxal-treated oocytes displayed more DNA double strands breaks and this can also be decreased by treatment of resveratrol. Further investigation of these processes revealed that methylglyoxal may affect the oocyte quality by resulting in excessive reactive oxygen species production, aberrant mitochondrial distribution and high level lipid peroxidation, and resveratrol can block these cytotoxic changes. Collectively, our results showed that resveratrol can protect the oocytes from methylglyoxal-induced cytotoxicity and this was mainly through the correction of the abnormity of cellular reactive oxygen species metabolism.
Highlights
Methylglyoxal (MG), a highly reactive dicarbonyl compound, is a metabolic byproduct of glucose[1]
Resveratrol protects against MG-induced DNA breaks Recent studies have shown that MG may lead to oxidative damage of oocytes via the formation of reactive oxygen specie (ROS)[10,11]
Oocytes with over 10 foci in nucleus obviously increased (Fig. 1A, B). This MG-induced DNA damage could be prevented by different concentrations of resveratrol and oocytes with high intense c-H2AX staining significantly reduced in a dose-dependent manner (Control: 11.261.5%, n = 121; MG-treated: 71.864.1%, n = 120; resveratrol-MG-treated: 5 mM resveratrol: 55.562.0%, n = 116; 10 mM resveratrol: 33.762.9%, n = 128; 25 mM resveratrol: 30.662.0%, n = 112) (Fig. 1A, B)
Summary
Methylglyoxal (MG), a highly reactive dicarbonyl compound, is a metabolic byproduct of glucose[1]. MG attacks the arginine, lysine and cysteine residues of proteins to form irreversible advanced glycation end products (AGEs), which subsequently leads to more cross-linking and degradation of proteins[5] This accumulation of AGEs is considered to be responsible for the long-term complications of diabetes and ageing[6,7]. Oocytes maturation can be seriously disturbed by the MG-induced breakage of DNA, disruption of spindle assembly, depletion of anti-oxidation enzymes and disorder of mitochondrial function. All of these may root in the elevation of intracellular reactive oxygen specie (ROS) level and this implies that a supplement of anti-oxidant may counteract the deleterious effect of MG on oocytes
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