Triptolide Exposure Induces Oxidative Stress And Decreases Oocyte Quality In Mouse

The female reproductive process is the basic physiological pathway of mammalian species reproduction,including oocyte meiosis,follicle development,oocyte genesis,fertilized egg and embryo formation and development,etc.The influence of any process may eventually be reflected in the damage of female mammals themselves or their offspring.Triptolide,a major active ingredient isolated from Tripterygium wilfordii,its preparation has been on the market and widely used in clinic.Through further study on the characteristics of triptolide,it can be found that triptolide has stable chemical properties and strong physiological activity in vivo.However,while triptolide shows high biological activity,it also has high toxicity.In clinical studies,triptolide has toxic side effects on the heart,kidney,liver and reproductive organ.The toxicity of triptolide on male reproductive system has been reported,but the effect of triptolide on female reproductive system is less studied.Therefore,concentration gradients of triptolide exposure in mouse were established by gavage at doses of 0,30,60 and 90 μg/kg/day.After 28 days of triptolide administration,with the increase of exposure dose,the body weight of mouse decreased,ovarian morphology decreased and ovarian coefficient decreased.Triptolide impaired the normal development of follicles,decreased preovulatory follicles and increased atretic follicles.At the same time,oocytes development is affected,which is manifested as reduced number of collected oocytes at GV stage and MII stage,oocytes meiosis spindle abnormality,chromosome disorder,microtubule stability abnormality,oocyte oxidative stress which induce early apoptosis and DNA breakage,abnormal mitochondrial distribution and function,abnormal lysosome distribution and autophagy,abnormal histone methylation level,which together impair oocytes development.These adverse effects could be associated with oxidative stress induced by triptolide.In conclusion,our results suggest that triptolide exposure in vivo impaired female reproductive function in mouse.