Molecular and Cellular Pathways and Mechanisms of Antioxidant Compounds Against Oxidative Stress in Obesity-associated Male Infertility: A Comprehensive Review.

Obesity is a condition characterized by abnormal or excessive fat accumulation that increases the risk of various health conditions. Obesity is highly linked to reduced male fertility parameters, including semen volume, sperm count and concentration, motility, vitality, and normal morphology. This connection is primarily driven by oxidative stress (OS) and chronic low-grade inflammation, which disrupt normal spermatogenesis and sperm function, with a higher occurrence of sperm DNA damage, impacting male fertility and potentially affecting pregnancy outcomes. This review aims to investigate, in obese men, the molecular and pathophysiological mechanisms through which various antioxidants exert beneficial effects on spermatogenesis, chronic inflammation and oxidative stress. A comprehensive literature review was conducted to assess the effectiveness of antioxidants in treating male infertility associated with obesity, focusing on vitamins, minerals, co-enzymes, antioxidant enzymes, and various polyphenols. This review analyzes the activity of antioxidant molecules, individually or synergistically with other bioactive compounds, and the pathophysiological pathways they may affect, such as the scavenging of free radicals, enhancement of cellular repair, and modulation of inflammation, to protect sperm in obese infertile men. Treatment with antioxidants, either as a primary therapeutic option or as dietary supplementation, appears to be positively associated with improvements in sperm parameters related to obesity. This highlights the pharmacological properties of antioxidant compounds, particularly their effects on dysregulated physiological processes in male fertility, including inflammatory, oxidative, and hormonal processes. Future studies should also determine the dosages of antioxidants, their side effects, and the synergistic effects of different types of antioxidants for infertility treatment in obese men. Thus, it is suggested that, together with other treatment options, obese infertile men be supplemented with antioxidants. However, further research on specific categories of antioxidants is needed to confirm this fully.