title: 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.
authors.affiliation: Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Fu-Jen
authors.initials: FJ
authors.lastname: Huang
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Chin
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Chan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D004789:Enzyme Activation; D005260:Female; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011765:Pyruvaldehyde / Q000378:metabolism* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D011765:Pyruvaldehyde; D053148:Caspase 3; D000077185:Resveratrol