Royal Jelly ameliorates 6-mercaptopurine induced spermatogenesis impairment and testicular apoptosis by regulating PI3K/AKT pathway in male rats

Abstract Testicular apoptosis is an obvious adverse effect of many chemotherapeutic agents.one of these chemotherapeutic drugs is 6-mercaptopurine (6MP) which has a powerful anticancer effect. On the contrary, it has an adverse effect on the male reproductive system. This study aimed to evaluate the prospective ameliorative effects of Royal Jelly (RJ) on 6MP induced testicular apoptosis and investigate the mechanistic pathway of protection. For this aim, forty male adult albino rats were divided into four equal groups (n= 10): control rats, RJ group (200 mg/kg.b.wt. of RJ for 30 day P.o.), 6MP group (5 mg/kg.b.wt of 6MP for 20 day P.o.), and RJ+6MP group pretreated with RJ (200 mg/kg.b.wt. for 10 day P.o.), and continued with 6MP (5 mg/kg.b.wt, P.o) for 20 day. After 30 days blood samples, epididymis and testis were collected to investigate sex hormones, sperm parameters, histological and molecular changes of testicular tissues, that include anti-oxidants activity, caspase-3, TNF-α, gene expression of Androgen receptors (AR) and P53 also protein concentration of PI3K, AKT, Nrf2 and HO1were estimated. The results of our study revealed that Pretreatment of Royal Jelly (RJ) abrogated 6MP induced spermatogenesis impairment by ameliorating sperm count, motility and morphology, regulating AR mRNA expression and sex hormones levels. RJ ameliorated testicular damage of 6MP exposed rats through restoring testicular antioxidant/oxidative redox, inhibiting caspase-3 activity and P53 mRNA expression as well as regulation of PI3K, AKT, Nrf2 and HO1 protein levels. Our data concluded that RJ protected testicular tissue from 6MP induced apoptosis by regulation PI3K/AKT pathway.