Zuogui Wan rescues the high-glucose-induced damaging effects on early embryo development

Background: High concentration of glucose in culture medium affects the developmental process and the quality of the pre-implantation embryo. This study examined the effects of Zuogui Wan (ZGW) supplementation on early embryo development cultured in high-glucose medium. Methods: Embryos were cultured in high-glucose medium with or without ZGW supplementation. Developmental rate and competence was evaluated by cleavage rate, blastocyst rate, and blastocyst total cell number, reactive oxygen species (ROS) level, glutathione (GSH) concentration, and metabolome were also measured to determine the effect of ZGW on embryo development at the cellular level. Results: Compared with the vehicle group, supplementation of 0.01 % ( v/v) ZGW to high-glucose medium significantly increased cleavage rate (80.1 +/- 1.0 % vs 72.1 +/- 1.3 %), blastocyst rate (50.5 +/- 1.0 % vs 41.3 +/- 1.7 %), and blastocyst total cell number (63.2 +/- 2.2 vs 57.2 +/- 1.6). ROS level was lower and GSH concentration in blastocysts was higher in ZGW-treated group. Metabolomic analysis found that the ratio of glucose to succinic acid and glucose to fumaric acid were lower in the ZGW-treated group. Conclusions: Developmental rates of zygotes in high-glucose culture medium were significantly lower than those in regular culture medium. ZGW supplementation significantly improved embryo development and quality in high-glucose medium. Supplementing ZGW in high-glucose medium also significantly increased total cell number and GSH concentration but decreased ROS level in blastocysts likely by modifying metabolic profile during embryo development. Together, these data suggest that supplementation of ZGW rescues high-glucose-induced detrimental effects on pre-implantation embryo development.