Kisspeptin signalling in male reproduction: Molecular mechanisms, biomarker potential, and therapeutic opportunities

Abstract: Kisspeptin, a peptide encoded by the KISS1 gene, has emerged as a principal regulator of the hypothalamic-pituitary-gonadal axis and plays a fundamental role in male reproductive physiology. Beyond its established function in stimulating gonadotropin-releasing hormone secretion, accumulating evidence indicates that kisspeptin and its receptor are expressed in peripheral reproductive tissues, including the testes and spermatozoa, where they influence steroidogenesis, spermatogenesis, sperm maturation, motility, capacitation, and fertilization. Alterations in kisspeptin signalling have been implicated in delayed puberty, hypogonadotropic hypogonadism, impaired spermatogenesis, and male infertility, highlighting its diagnostic and therapeutic relevance. Furthermore, kisspeptin concentrations in circulating and seminal plasma have been investigated as potential biomarkers of male reproductive health. At the same time, kisspeptin-based therapies are being explored for the management of reproductive endocrine disorders. This review critically synthesizes current knowledge on the molecular biology, physiological functions, and clinical significance of kisspeptin in male reproduction. It also examines emerging evidence supporting the translational applications of kisspeptin in diagnosis and treatment, identifies current controversies and knowledge gaps, and proposes future research directions to facilitate the integration of kisspeptin signalling into clinical and reproductive medicine.