Serum exosomes from hepatitis B virus–infected patients inhibit glycolysis in Sertoli cells via miR-122-5p/ALDOA axis

Hepatitis B virus (HBV) infection is associated with male infertility. The mechanism includes an increase in chromosomal instability in sperm, which has an adverse effect on sperm viability and function. Sertoli cells (SCs) are vital in spermatogenesis because they use glycolysis to provide energy to germ cells and themselves. HBV infection impairs sperm function. However, whether HBV infection disrupts energy metabolism in SCs remains unclear. This study aimed to determine the role of serum exosomes of HBV-infected patients in SC viability and glycolysis. Serum exosomes were obtained from 30 patients with (HBV+_exo) or without (HBV–_exo) HBV infection using high-speed centrifugation and identified by transmission electron microscopy and western blot analysis. Cell viability is determined by CCK-8 assay. Glycolysis is determined by detecting extracellular acidification rate and ATP levels. miR-122–5p expression levels are detected by quantitative RT-PCR, and a dual-luciferase gene reporter assay confirms the downstream target gene of miR-122–5p. Protein expression is determined by western blot analysis. The results show that HBV+ _exo inhibited cell viability, extracellular acidification rate, and ATP production of SCs. miR-122–5p is highly expressed in HBV+ _exo compared with that in HBV–_exo. Furthermore, HBV+ _exo is efficiently taken up by SCs, whereas miR-122–5p is efficiently transported to SCs. miR-122–5p overexpression downregulates ALDOA expression and inhibits SC viability and glycolysis. However, ALDOA overexpression reverses the effects of miR-122–5p and HBV+ _exo on SC viability and glycolysis. HBV+ _exo may deliver miR-122–5p to target ALDOA and inhibit SC viability and glycolysis, thus providing new therapeutic ideas for treating HBV-associated male infertility.