Autophagy may play an important role in varicocele.

Abstract

The present study aimed to determine the expression of autophagy and investigate whether the hypoxia-inducible factor 1α (HIF-1α)/BCL2 interacting protein (BNIP3)/Beclin-1 autophagy signaling pathway serves an important role in activating autophagy in varicocele (VC) rat testes cells. Furthermore, the current study aimed to explain the possible association between autophagy and apoptosis. A total of 48 adult male Sprague Dawley rats were divided into group A (control), group B (VC 15-day), group C (VC 30-day) and group D (VC 45-day), with 12 rats in each group. The rats in group A did not receive any interventions, and in groups B, C, and D the VC model was established simultaneously. At 0, 15, 30, and 45 days, an orchidectomy on the left testes was performed in groups A-D, each on its respective day. Transmission electron microscopy was used to investigate the expression of autophagy. Compared with groups A and B, it was demonstrated that the expression of autophagy in groups C, and D was significantly increased. Hematoxylin and eosin staining revealed that as the rats survived VC longer, the testicular tissue damage became more serious. Furthermore, the Johnson score revealed that VC impaired the spermeiogenesis function of the male rats. Additionally, it was demonstrated that the apoptosis index of the seminiferous epithelia cells in VC rat testes increased over time, as measured using TUNEL staining. Immunohistochemical analysis revealed that as the VC was prolonged, the expression of HIF-1α gradually increased while the expression of (apoptosis regulator Bcl-2) Bcl-2 gradually decreased. Furthermore, western blot analysis revealed that the protein expression of Bcl-2 decreased and apoptosis regulator Bax increased. Furthermore, HIF-1α, BNIP3, Beclin1 and microtubule associated protein 1 light chain 3 α (LC3)II/LC3I expression gradually increased. However, significant increases in Beclin 1 and LC3II/LC3I were only observed between the day 0 and day 30 groups. In addition, the expression of p62 significantly increased between day 0 and day 15, but gradually decreased between day 15 and day 45. The results of the present study revealed that VC can lead to testicular tissue hypoxia, and that the HIF-1α/BNIP3/Beclin1 autophagy signaling pathway may upregulate autophagy in VC rats testes. Thus, the association between autophagy and apoptosis may serve an important role in male infertility caused by VC.