Effects of Omega-3 Fatty Acids on Testosterone Levels and Semen Quality in Albino Mice: An Integrated In Vitro and In Vivo Study

Abstract

Abstract

Male infertility, affecting approximately 40% of infertile couples globally, is significantly associated with declining testosterone levels and compromised semen quality. Omega-3 polyunsaturated fatty acids (PUFAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are recognized for their anti-inflammatory, antioxidant, and membrane-stabilizing properties. While epidemiological studies have suggested benefits in human male fertility, comprehensive mechanistic insights from preclinical models remained limited. This study utilized an integrated in vitro (Leydig and Sertoli cells) and in vivo (albino mice) approach to bridge cellular mechanisms with physiological responses. We investigated the dose-dependent effects of omega-3 on steroidogenesis, optimization of sperm parameters, and redox and endocrine interactions. Our findings demonstrated that medium-dose omega-3 supplementation significantly elevated testosterone levels, improved sperm motility and morphology, and reduced testicular oxidative stress in vivo. In vitro results showed synergistic stimulation of Leydig cell steroidogenesis, enhanced Sertoli cell function, and differential fatty acid incorporation. These findings provide robust evidence supporting omega-3 supplementation as a promising nutritional strategy for male infertility, particularly in cases involving oxidative stress, and highlight the utility of spatial lipidomics for understanding testicular lipid dynamics.