Effect Of Roundup On Mouse Embryo Development And Implantation

Roundup? is one of the most widely applied herbicides in the world.Due to the extensive application and even abuse of Roundup,its residues have been detected in soil,water and even agricultural products.This poses a very high risk of exposure to humans and mammals.And thus assessment on the safety of Roundup is becoming one of the more urgent and important scientific issues.According to published researches,Roundup are toxic to liver,kidney,nervous system,and reproductive system.Current researches on reproductive toxicity of Roundup to mammals mainly focus on males,toxicity and mechanism of which are relatively clear.However,toxicity of Roundup to mammal embryos is unclear.Here,we explored the effects of Roundup on the quality,development,implantation and post-implantation development of mouse early embryo.The results we got are as follows.Firstly,we set three Roundup doses for exposure experiments in vivo,which are low dose(300 mg/kg·bw),medium dose(650 mg/kg·bw),and high dose(1000 mg/kg·bw)according to the Roundup LD50 of acute oral exposure to mice to explore the effect of Roundup acute oral exposure in the quality and development of mouse early embryo in vivo.Results show that after low,medium,and high doses of Roundup exposure,there is no significant differences on No.of 8-cell embryo in contrast to control group,but the No.of blastocyst decreased significantly,indicating abnormal embryo development in vivo;We further monitored ROS and calcium ion concentration of 8-cell embryo in vivo,and found that after exposure of low,medium and high doses of Roundup exposure,8-cell embryo had oxidative stress and calcium ion concentration increased in contrast to control group.Besides,results of apoptosis / differentiation staining of blastocyst showed that after low,medium,and high doses of Roundup exposure,there was no significant difference in No.of blastomeres of blastocyst,but the apoptosis index increased significantly.These indicate that Roundup exposure causes decrease of embryo quality.The above results indicate that low,medium,and high doses of Roundup exposure has adverse effects on the quality and development of mouse early embryo in vivo.Then,we established the in vitro model of early embryo exposure to Roundup to eliminate the interference of damage to the matrix caused by Roundup which may do harm to embryo,and explored whether Roundup has direct toxic effects on embryo.Results show that there is a dose-dependent relationship between Roundup dilution and blastocyst developmental rate in vitro at Roundup dilution from 1:100K to 1:1M: blastocyst developmental rate rises as Roundup dilution increases.Subsequent experiments were conducted with the Roundup dilution at 1:400K,in which blastocyst developmental rate in vitro is nearly half of which in control group.At this dilution,it is monitored that oxidative stress occurred and calcium ion concentration increased in 8-cell embryo.Besides,apoptosis / differentiation staining of blastocysts revealed that although there was no significant difference in the number of blastocyst blastomeres compared to the control group,the apoptosis index increased significantly.The above results are consistent with results of early embryo experiments in vivo,indicating that there is a direct the adverse effect of Roundup exposure on the quality and development of early embryos.Finally,considering that the quality and developmental abnormalities of pre-implantation embryos will adversely affect the embryo implantation process and post-implantation intrauterine development,we further explored the acute oral exposure of Roundup to embryo implantation and post-implantation intrauterine development.Results show that No.of D9 embryo implantation sites in the low,medium,and high dose of Roundup exposure groups decreased significantly in contrast to control group,indicating partially implantation failure;Besides,results show that litter size and body weight of F1 offspring decreased significantly in medium and high dose of Roundup exposure groups in contrast to control group,which indicates that medium and high dose of Roundup exposure caused abnormal embryo development in uterus.However,decrease of litter size and body weight of F1 offspring in the low dose of Roundup exposure group was not significant,which may be due to the damage to the embryo within its tolerable range,and the embryos can gradually recover during the development process in uterus.Above all,we found that Roundup has a direct toxic effect on the quality,development,implantation and post-implantation development of early embryo of mouse.This study supplements the early embryo toxicity part of reproductive toxicity of Roundup,and provides important data on the toxicity of embryos for Roundup toxicity researches and establishment of Roundup safety evaluation system.In addition,this study provides a theoretical reference for the safety protection of women with high exposure risks of Roundup in production activities,and provides a theoretical basis for pesticide regulatory authorities to regulate the amount of Roundup application.