Deoxycholic Acid Impairs Human Sperm Quality and Function Through Oxidative Stress-Driven Damage

Infertility is a growing global health concern, with male infertility contributing to nearly half of all cases. While conventional semen analysis often overlooks functional impairments, oxidative stress has emerged as a key factor affecting sperm quality. Notably, oxidative stress is elevated in obesity, a rising epidemic affecting more than 1 in 8 people worldwide. This study examines the role of deoxycholic acid (DCA), a secondary bile acid that is elevated in obesity, and its potential to induce oxidative stress and impair sperm function. Semen samples from healthy donors were incubated with DCA, and its effects on sperm motility, viability, capacitation, and oxidative stress markers were assessed. Sperm motility and viability were evaluated using computer-assisted semen analysis (CASA) and hypo-osmotic swelling (HOS) tests, while sperm capacitation was measured via tyrosine phosphorylation (P-Tyr) and acrosome reaction (AR). Oxidative stress markers were quantified using flow cytometry. While progressive motility and viability remained unchanged, DCA reduced hyperactive motility, P-Tyr, and acrosome reaction and increased oxidative stress markers in spermatozoa. These findings suggest that secondary bile acids can disrupt sperm function through oxidative mechanisms, affecting non-conventional semen parameters that may go undetected in standard analyses. This underscores the gut-testis axis's role in male infertility and highlights the need for more comprehensive diagnostics and targeted therapies.