Resveratrol protects against methylglyoxal‐induced apoptosis and disruption of embryonic development in mouse blastocysts

Abstract

Methylglyoxal (MG) is a glucose metabolite. Diabetic patients have increased serum levels of MG, and MG is also implicated in tissue injury during embryonic development. In the present work, we show that MG induces apoptosis in the inner cell mass of mouse blastocysts and inhibits cell proliferation. Both effects are suppressed by resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties. MG-treated blastocysts displayed lower levels of implantation (compared to controls) when plated on culture dishes in vitro and a reduced ability to proceed to later stages of embryonic development. Pretreatment with resveratrol prevented MG-induced disruption of embryonic development, both in vitro and in vivo. Further investigation of these processes revealed that MG directly promotes reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential (MMP), and activation of caspase-3, whereas resveratrol effectively blocks MG-induced ROS production and the accompanying apoptotic biochemical changes. Our results collectively imply that MG triggers the mitochondrion-dependent apoptotic pathway via ROS generation, and the antioxidant activity of resveratrol prevents MG-induced toxicity.

Methylglyoxal and methylglyoxal‐modified collagen as inducers of cellular injury in gingival connective tissue cells

“…MGO may induce apoptosis in several cell types, including human blood mononuclear cells, human endothelial cells, blastocysts and hepatic Hepg2 cells . Moreover, reactive oxygen species have been identified in the induction of cell death by MGO .…”

“…It is important to consider that besides the pathological modification of extracellular matrix proteins, MGO may directly affect cell viability and function in several cell types . Nevertheless, the potential cytotoxic effects of MGO on periodontal cells remain largely undefined.…”

Induction of mitochondrial apoptotic pathway in triple negative breast carcinoma cells by methylglyoxal via generation of reactive oxygen species

“…Chemotherapeutic strategies are often designed to increase cellular ROS production which inflicts irreparable cellular damage resulting in apoptosis . MG has been identified as a potent oxidant that can promote exuberant ROS generation and therefore the ability of MG to produce ROS in MDA MB 231 cells was studied. Cells were treated with different concentrations of MG (0.4, 0.6, 0.8, and 1.0 mM) and the generated ROS was measured using the DCFH‐DA fluorescence assay.…”

“…Production and accumulation of AGEs has been reported to induce apoptosis by promoting pro‐apoptotic cytokine production and reactive oxygen species (ROS) generation . In addition to AGEs, MG by itself can trigger apoptosis by oxidative DNA damage, ROS production, and altering the mitochondrial complex I . Other studies on the apoptogenic and anti‐proliferative effect of MG indicate involvement of diverse signal transduction pathways and molecular events in different cell types.…”

Endoplasmic Reticulum Stress Signaling in Mammalian Oocytes and Embryos: Life in Balance

“…Antioxidants can improve oocyte quality and enhance embryo development (Huang et al, 2013; Ideta et al, 2012; Orsi and Leese, 2001; Takeo et al, 2014; Wang et al, 2014a) and also protect against peroxide-induced damage (Yu et al, 2014) and other stress induced damage (Cebrian-Serrano et al ., 2013; Koyama et al ., 2012; Sakatani et al ., 2007) in embryos and oocytes (Devine et al ., 2012). Additionally, reduced glucose availability in vitro has long been recognized as beneficial to embryos (Chatot et al, 1989; Leese, 2012), although glucose starvation can actually increase ROS production and is not beneficial (Jansen et al, 2009).…”