Phytochemicals Targeting Oxidative Stress in Male Infertility: Molecular Mechanisms, Cellular Protection, and Translational Perspectives

Abstract

Male infertility is a heterogeneous reproductive disorder associated with impaired spermatogenesis, abnormal sperm maturation, endocrine dysfunction, varicocele, infection, environmental exposures, metabolic disease, and idiopathic factors. Oxidative stress is an important mechanism linking several of these conditions to impaired sperm function. Excessive reactive oxygen species can cause lipid peroxidation, protein oxidation, mitochondrial dysfunction, DNA damage, apoptosis, altered autophagy, and ferroptosis, whereas physiological reactive oxygen species are required for normal sperm signaling and fertilization. Phytochemicals have attracted interest because they may restore redox homeostasis through direct antioxidant activity and modulation of endogenous antioxidant, inflammatory, mitochondrial, and cell-death pathways. This review summarizes primary research investigating phytochemicals targeting oxidative stress in male reproductive dysfunction, with emphasis on chlorogenic acid, lycopene, curcumin, astaxanthin, flavonoids, epigallocatechin-3-gallate, resveratrol, Morinda officinalis polysaccharides, and apigenin. Human and human-sperm studies provide evidence for effects on sperm motility, viability, oxidative damage, DNA integrity, and cryopreservation outcomes, while animal and cellular studies provide additional evidence involving NRF2, mitochondrial function, SIRT1/PGC-1α, apoptosis, inflammation, and the GSH–GPX4 ferroptosis pathway. However, most mechanistic evidence remains preclinical, and findings vary according to compound, concentration, formulation, and experimental model. Phytochemicals should therefore be considered promising experimental redox modulators rather than established treatments for male infertility. Future clinical studies require standardized preparations, biologically achievable dosing, oxidative-stress phenotyping, rigorous mechanistic assessment, and fertility-relevant outcomes.