Acupuncture modulates ovarian senescence through metabolic reprogramming: A multi-omics investigation in chemotherapy - induced POF model

Abstract

Premature ovarian failure (POF) is a common female endocrine disorder in women, and there is currently no effective pharmacological treatment available. Acupuncture, an important component of traditional Chinese medicine, has demonstrated clinical efficacy in improving ovarian function in patients with POF; however, its underlying mechanisms remain unclear. This study systematically investigated the therapeutic mechanisms of acupuncture in cyclophosphamide (CTX)-induced POF through combined analysis of proteomic and metabolomic data. In a rat model of chemotherapy-induced ovarian dysfunction, 28-day acupuncture intervention significantly delayed the pathological alterations in ovarian morphology and slowed the decline of endocrine function, as evidenced by normalized serum FSH, LH, and AMH levels. Metabolomic profiling identified 1683 differential metabolites across positive/negative ion modes, with taurine-hypotaurine metabolism (KEGG map00430) emerging as a key antioxidant axis, correlating with enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Proteomic analysis revealed acupuncture-mediated reversal of 115 ovarian proteins, particularly PPAR signaling components (FABP5, ADIPOQ and PLIN1), which orchestrated lipid metabolic reprogramming. Combined analysis of proteomic and metabolomic data demonstrated strong Spearman correlations between metabolic regulators (taurine, d-aspartate) and ovarian reserve markers, while PPAR-associated proteins exhibited network connectivity with oxidative stress mediators. These findings establish that acupuncture delays POF through synchronized modulation of metabolic flexibility and PPARγ-driven antioxidant defense, providing a novel systems biology framework for understanding traditional medicine interventions in reproductive aging.