Effects Of Disulfiram On Reproductive Ability In Female Mice

In the process of assisted reproduction,the high oxygen environment in vitro is easy to cause oxidative damage to oocytes.In order to obtain a sufficient number of transplantable embryos,women or female economic animals usually need to perform multiple superovulation.The price of hormone drugs is high,and a large number of hormone drugs are easy to induce ovarian hyperstimulation syndrome(OHSS).Disulfiram(DSF)is clinically used to give up alcohol addiction,and its price is low.In recent years,DSF has been found to play an important role in the treatment of cancer,inflammation and obesity.In tumor cells,DSF promotes tumor cell apoptosis by increasing the level of reactive oxygen species and decreasing the level of glutathione.In the process of treating inflammation,obesity and organ damage,DSF can reduce the level of reactive oxygen species in cells,increase the level of glutathione,play an antioxidant role,and reduce the damage of diseases to the body.Whether DSF plays an antioxidant role in oocytes is still unknown.In addition,the impact of DSF on pregnant women and fetuses in the early stage of pregnancy has not yet been determined.In this study,mice were used as models to explore the effects of DSF on estrus cycle,reproductive hormones,ovulation number,oocyte quality,embryo development,uterine volume and vascularization,conception rate and offspring breeding.The main experimental results obtained in this study are as following:1.Using 50 mg/kg or 100 mg/kg DSF in the estrus of mice can prolong the estrus period from 1.67 ± 0.22 days to 2.92 ± 0.28 days or 3.42 ± 0.15 days,respectively.The concentration of estradiol in serum of DSF group decreased and the concentration of follicle-stimulating hormone increased at each stage of the estrus cycle.2.In mice treated with 50 mg/kg DSF,the average number of ovulation increased from25.70 ± 1.71 to 37.85 ± 2.35,the level of reactive oxygen species in oocytes decreased,the level of glutathione increased,the mitochondrial membrane potential increased,and the in vitro fertilization rate of oocytes increased.3.Compared with the control group,the average number of blastocysts obtained by mice using DSF in early pregnancy increased from 14.67 ± 1.687 to 23.33 ± 1.563.At the same time,the uterine horn volume and vascularization of mice in DSF group increased,the pregnancy rate increased by 22%.4.Adding DSF into cell culture medium can up-regulate the m RNA levels of angiogenesis-related genes(Vegf),follicular development-related genes(C1qtnf3,m TOR and Pi3k),ovulation-related genes(Mapk1,Mapk3 and p38Mapk),antioxidant-related genes(Gpx4 and Cat)in mouse ovarian granulosa cell.In conclusion,DSF can improve the ovulation rate of mice,and improve the antioxidant capacity and in vitro fertilization capacity of oocytes.In addition,DSF may promote angiogenesis by up-regulating the expression of Vegf,which is helpful for pregnancy and embryo development.This study provides a theoretical basis for the effect of DSF on female reproductive capacity of mammals,and provides a reference for clinical use of DSF.