The role of the cGAS-STING pathway in male reproductive disorders

Recently, the cGAS-STING signaling pathway has garnered significant attention due to its role in the pathogenesis of various disorders, including cancer, autoimmune diseases, and auto-inflammatory diseases. This pathway is a novel innate immune recognition mechanism that functions as a cytoplasmic DNA sensor. It mediates protective immune responses against tumor-derived DNA, DNA-containing pathogens, and cytoplasmic DNA (nuclear and mitochondrial DNA) by producing a range of inflammatory cytokines. Although the normal activation of cGAS-STING signaling induces innate immunity against infections, aberrant activation of the cGAS-STING axis is associated with excessive inflammatory responses, leading to an immune system attack on normal tissues and contributing to the development of autoimmune diseases. Activation of the cGAS-STING also emerges as a double-edged sword in different types of cancer. There are different perspectives on the abnormal function of the cGAS-STING pathway in various male reproductive disorders. Understanding the factors that regulate the cGAS-STING pathway and its involvement in male reproductive system issues can help develop new strategies for prevention and treatment. This review focuses on the role of the cGAS-STING signaling pathway in male reproductive-related diseases. We also explore targeting the cGAS-STING signaling pathway for the prevention and treatment of male reproductive diseases.