Rutin rescues oocyte developmental competence in primary ovarian insufficiency by restoring mitophagy and suppressing pyroptosis.

Primary ovarian insufficiency (POI) is a major cause of female infertility and endocrine dysfunction, for which effective therapies remain limited. We investigated whether rutin, a bioactive compound from traditional Chinese medicine, protects ovarian function in POI by regulating mitochondrial homeostasis and pyroptosis. In vitro assays using chemically injured oocytes showed that rutin alleviated mitochondrial defects, rescued developmental arrest, enhanced antioxidant signaling, promoted mitophagy, and reduced inflammatory cell death. In a cyclophosphamide-induced murine POI model, rutin restored estrous cyclicity, improved follicle development, normalized hormone levels, and enhanced ovulation, litter outcome, and in vitro-fertilization (IVF)-related developmental competence. Ovarian histological and molecular analyses further showed reduced inflammasome-related pyroptotic signaling, lower oxidative stress levels, and improved mitochondrial integrity. These findings identify rutin as a promising ovarian-protective candidate in POI-associated infertility and support further investigation of its therapeutic potential in female reproductive disorders.