Lycopene Attenuates Hypoxia-Induced Testicular Injury by Inhibiting PROK2 Expression and Activating PI3K/AKT/mTOR Pathway in a Varicocele Adult Rat

Abstract

Purpose. The aim of this study was to evaluate the effect of lycopene on hypoxia-induced testicular injury in rat model and explore the underlying mechanism. Methods. Six-week-old male Wistar rats (n = 36) were randomly divided into three groups (n = 12/group): a normal group (NG, sham control), a varicocele group (VG), and a varicocele treated by lycopene group (VLG). Bilateral renal veins constriction was performed on rats in VG and VLG. Simultaneously, rats in VLG were treated to lycopene by intragastric administration. Four weeks later, sperm was collected for sperm analysis. Testes and epididymides were harvested for morphological change analysis, histologic analysis, ELISA, qRT-PCR, and western blot. Results. Our observations were that lycopene improved the hypoxia-induced testicular injury in vivo. Prokineticin 2(PROK2) and prokineticin receptor 2 (PROKR2) were overexpressed in VG ( $P$  < 0.01), and lycopene inhibited the PROK2 expression ( $P$  < 0.01). Proliferating cell nuclear antigen (PCNA) and sex hormones were increased by lycopene in VLG ( $P$  < 0.05). Lycopene restored the quality and activity of sperm by blocking PROK2 expression ( $P$  < 0.05). The expression of VEGF was increased, as HIF-1/NF-κB pathway was upregulated in VLG ( $P$  < 0.05). Meanwhile, expression of pAKT/AKT in VLG was higher than that in VG ( $P$  < 0.05). In addition, lycopene reduced levels of interleukin-1β (IL-1β) and interleukin-2 (IL-2) in VLG ( $P$  < 0.05), compared to NG. Conclusions. Lycopene improved the hypoxia-induced testicular injury by inhibiting the expression of PROK2 and decreasing levels of IL-1β and IL-2, which might show us a novel and promising treatment for varicocele testicular injury.