Effect of acupuncture on sperm mitochondrial function: A study based on the Keap1–nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway
Introduction: Asthenozoospermia, characterized by impaired sperm motility, is a major contributor to male infertility. Mitochondrial dysfunction driven by oxidative stress plays a critical role in its pathogenesis, and the Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway serves as the principal regulator of cellular antioxidant defense. Acupuncture has shown clinical benefits for sperm quality, yet its underlying molecular mechanism remains inadequately defined.
Objective: To examine the regulating influence of acupuncture on mitochondrial oxidative stress in asthenozoospermic rat sperm and to clarify its underlying mechanism related to the Keap1–Nrf2/HO-1 signaling pathway.
Methods: Thirty-two male Sprague–Dawley rats were randomly assigned to four groups (n=8): normal, model, acupuncture, and curcumin. After model induction with ornidazole, the acupuncture group received electro-acupuncture (2 Hz, 2 mA) at Guanyuan (CV4), Shenshu (BL23), Zusanli (ST36), and Sanyinjiao (SP6) for 28 days, while the curcumin group received oral curcumin (300 mg/kg/day). Sperm motility was assessed using computer-assisted sperm analysis. Mitochondrial membrane potential (MMP) was measured using JC-1 staining. Oxidative stress markers were evaluated by biochemical assays. Keap1, Nrf2, and HO-1 mRNA and protein expression were determined by real-time quantitative polymerase chain reaction and Western blotting.
Results: Compared with the normal group, the model group exhibited significantly reduced sperm motility and MMP, elevated malondialdehyde levels, and decreased superoxide dismutase and glutathione peroxidase activities (p<0.01). Both acupuncture and curcumin effectively reversed these changes (p<0.01). Furthermore, acupuncture downregulated Keap1 expression while upregulating Nrf2 and HO-1 at both transcriptional and translational levels (p<0.01), consistent with the curcumin group.
Conclusion: Acupuncture improves sperm motility in ornidazole-induced asthenozoospermic rats by stimulating the Keap1–Nrf2/HO-1 signaling pathway, hence reducing oxidative stress, maintaining mitochondrial function, and increasing antioxidant capacity. These findings provide mechanistic evidence for acupuncture as a viable treatment for oxidative stress-related male infertility.
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