The Study Of The Effects On Neural Tube Development Of Mice Embryo Caused By Advanced Glycation End Products And Its Molecular Mechanism

Neural tube defects?NTDs?are a common congenital malformation of the central nervous system,including spina bifida and anencephaly.Our previous case studies have found that advanced glycation end products?AGEs?are associated with NTDs.However,the exact effect of AGEs on neural tube development remains unclear.In this study,C57BL/6 mouse embryos were used as experimental models to feed the commercial feed containing 3‰bovine serum albumin advanced glycation end product and 3‰bovine serum albumin for four weeks.To observe the effect of AGE-BSA on the development of neural tube in mouse embryo,detect the level of AGEs in the serum of mice,N?-?carboxymethyl?lysine?CML?,N?-?carboxyethyl?lysine?CEL?,malondialdehyde?MDA?,H₂O₂ and reactive oxygen species?ROS?levels in embryos,and to understand the exact effect of AGEs on neural tube development and its molecular mechanism.The results showed that AGE-BSA incubated with glucose and BSA increased NTDs significantly without hyperglycemia;The levels of AGEs in serum,CML,CEL,MDA,H₂O and ROS in embryos increased significantly;Vitamin E supplementation can significantly reduce AGE-BSA-induced NTDs and oxidative stress levels in mouse embryos.Since AGE-BSA is a multi-component mixture,it is particularly important to explore the effects of its precursor,methylglyoxal?MGO?,on embryonic neural tube development and its interaction with glyoxalase I?Glo1?,a key enzyme in glyoxal scavenging system.Therefore,we studied the effects of MGO on the development of embryonic neural tube,the level of MGH1 and Glo1 activity by intraperitoneal injection of different concentrations of MGO during pregnancy and co-incubation of normal mouse embryos with MGO.The results showed that intraperitoneal injection of different concentrations of MGO during pregnancy could induce NTDs in mouse with a significant dose-effect relationship.In vitro co-incubation of normal mouse embryos with MGO could significantly increase the content of MGH1 and inhibit the activity of Glo1 in mouse embryos.This study preliminarily confirmed that AGE-BSA could induce NTDs in embryos without hyperglycemia,which could significantly increase the levels of AGEs in serum,CML,CEL,MDA,H₂O₂ and ROS in embryos,and this process was related to the increased levels of oxidative stress in embryos at least to a certain extent.MGO as a precursor of AGEs,could induce NTDs by inhibiting Glo1 activity and increasing the formation of MGH1.