Effects Of Multi-Glycosides Of Tripterygium Wilfordii Hook. F On Testis Of Pubertal Rat And Its Mechanism

Objective The reproductive toxicity of multi-glycosides of tripterygium wilfordii hook.f (GTW) on testis of adult has been well-documented, however, much less is known about theeffects of GTW on developing testis. The purpose of the current study was to characterize thechanges of testicular histopathology and spermatogonia differentiation in testis of rats andtheir serum testosterone level after treated by GTW during the pubertal period, and to explorethe mechanism(s). Furthermore, the study recommends new idea to extensive studies of toxityin immature reproductive system caused by GTW. Methods Pubertal male Sprague-Dawleyrats (postnatal day35) were randomly divided into three groups(16/group), control group wasgavaged daily with1%carboxymethylcellulose (CMC)6ml/kg/day, low-dose group withGTW6mg/kg/day and high-dose group with GTW12mg/kg/day until adulthood (postnatalday63). Half of every group were sacrificed on postnatal day64and the other half on92,weight of testis and number of spermatogenic cells were evaluated, testicular histopathologychanges were detected by light microscope and transmission electron microscope techniques,expression of c-kit was examined by immunohistochemistry analysis to assess differentiationof spermatogonia， serum testosterone was measured by ELISA analysis. Results Onpostnatal day64, there were no obvious changes on histopathology and serum testosterone ofboth GTW groups(P>0.05), significant decrease of sermatogemic cell number and c-kitexpression were detected in both GTW groups(P<0.05). On postnatal day92, above changeswere not observed in low-dose GTW group(P>0.05), then significant decrease in number ofspermatogenic cells，expression of c-kit and level of serum testosterone were detected inhigh-does GTW group(P <0.01) with sertoli cells and blood-testis barrier(BTB) injured obviously. Conclusion GTW can cause injury in testis of pubertal rats which depends ondosage. It can cause tardive injury on seminaferous epithelium and BTB, damage of BTB mayplay an important role in reproductive toxicity on developing testis caused by GTW.Administration of GTW may not lead to adult but instead severe injury of immature malegonads. In addition, the study provide new idea to extensive studies of toxity in immature malegonads caused by GTW.