Effects of High Glucose on Autophagy and Apoptosis in Preimplantation Mouse Embryo Culture
Abstract
Maternal diabetes increases congenital malformations due to teratogenic effects of glucose on the developing embryo. High glucose culture alters preimplantation embryo development and is associated with increased oxidative stress. Apoptosis and autophagy are programmed cell death and survival mechanisms induced by oxidative stress, but their role in preimplantation diabetic embryopathy is poorly elucidated. It was hypothesized that high glucose culture would alter autophagic and apoptotic responses, and that they are dependent on the timing of high glucose culture initiation. Embryos were cultured with 0.2 mM (control) or 25 mM (high glucose) of D-glucose starting from the early (36 hpi) or late (48 hpi) 2-cell stage. High glucose culture impaired blastocyst development and total cell number but did not result in changes in apoptotic measures. Autophagic assessments showed increased autophagosome formation and maturation in hyperglycemic embryos when cultured from the early 2-cell stage, but not the late 2-cell stage. Overall, high glucose exposure appears to induce autophagy, but not apoptosis in embryos cultured under diabetically relevant glucose concentrations in the mouse embryo. These results increased the knowledge of mechanisms involved in the etiology of diabetic embryopathy.