Improving Sperm Quality and Hormonal Receptor Expression: N-acetylcysteine Treatment in Testicular Hypoxia

Testicular hypoxia, defined as insufficient oxygen supply to the testes, is a critical factor in male infertility and reproductive health issues. N-acetylcysteine (NAC), through its antioxidant properties and role as a glutathione (GSH) precursor, has been proposed as a protective agent against testicular hypoxia. This review evaluates whether NAC improves sperm quality and hormonal receptor regulation by reducing oxidative stress and modulating redox balance. We also summarize NAC’s effects on androgen receptors (ARs), estrogen receptors (ERs), and follicle-stimulating hormone receptors (FSHRs), highlighting its potential to influence spermatogenesis and endocrine function. Evidence from experimental studies and clinical trials suggests that NAC may improve sperm concentration, motility, morphology, and DNA integrity, though results on morphology remain inconsistent. Clinical findings indicate improvements in sperm parameters and oxidative stress biomarkers; however, effect sizes vary, and study limitations must be considered. This narrative review supports NAC as a potential therapy for hypoxia-related male infertility, while emphasizing the need for further clinical trials to clarify optimal dosing, treatment duration, and long-term safety.