Electroacupuncture Ameliorates Circadian Rhythm Disruption-Induced Oligoasthenospermia in Mice by Modulating the Sirt1/Nrf2 Antioxidant Signaling Pathway

Background: The growing prevalence of shift work and nocturnal light exposure in modern lifestyles has made circadian disruption an underrecognized environmental risk factor for male oligoasthenospermia. The core molecular network underlying circadian disruption-induced spermatogenic impairment remains incompletely understood, and targeted non-pharmacological interventions are limited. This study sought to identify candidate regulatory targets for circadian disruption-related oligoasthenospermia and investigate the protective mechanism of electroacupuncture. Methods: Gene sets associated with circadian rhythm and oligoasthenospermia were retrieved from GeneCards, OMIM, and GEO databases. Candidate hub genes and pathways were screened via intersection analysis, functional enrichment, and seven machine learning algorithms. A chronic jet lag mouse model was established and randomly divided into control, circadian disruption, and electroacupuncture groups. Sperm parameters, serum reproductive hormone levels, testicular and hepatic clock gene expression, testicular histology, oxidative stress status, and Sirt1/Nrf2 pathway activity were assessed. Results: Five hub genes linked to both circadian rhythm and oligoasthenospermia (IL1B, NFE2L2, PCNA, DMPK, MYH9) were identified, with functional enrichment highlighting pathways related to oxidative stress, gonadal development, and hormone regulation. In vivo, circadian disruption impaired sperm quality, dysregulated reproductive hormones, downregulated testicular clock genes, disrupted spermatogenic structure, elevated testicular oxidative stress, and suppressed the Sirt1/Nrf2 pathway. Electroacupuncture effectively reversed these pathological changes, restored hepatic clock rhythmicity, and upregulated key molecules of the testicular Sirt1/Nrf2 antioxidant pathway. Conclusions: Electroacupuncture ameliorates circadian disruption-induced spermatogenic impairment in mice. This protective effect is associated with the restoration of peripheral circadian rhythm and activation of the testicular Sirt1/Nrf2 antioxidant pathway.