Altered expression of the ferroptosis-related lncRNA TUG1 correlates with impaired sperm motility in asthenozoospermic men.

Asthenozoospermia, a common cause of male infertility characterized by reduced sperm motility, has been linked to oxidative stress and ferroptosis. Long non-coding RNAs (lncRNAs) are emerging regulators of redox balance and cell death. This study aimed to investigate the expression profile of the lncRNA taurine upregulated gene 1 (TUG1) and its relationship with ferroptosis-related dysfunction in spermatozoa from men with asthenozoospermia. Semen samples were collected from Iranian men with asthenozoospermia and normozoospermic controls. A bioinformatic screen of ferroptosis-associated lncRNAs identified TUG1 as a candidate biomarker, with several isoforms predicted to be dysregulated in asthenozoospermic sperm. Quantitative real-time PCR was used to assess the expression of TUG1, the ferroptosis-suppressing antioxidant enzyme gene glutathione peroxidase 4 (GPX4), and the somatic-cell markers CD5 and CD34. Lipid peroxidation was quantified by measuring malondialdehyde (MDA) levels. Associations among gene expression, oxidative stress markers, body mass index (BMI), and semen parameters were analyzed. Asthenozoospermic men exhibited significant upregulation of TUG1 and downregulation of GPX4 compared with normozoospermic controls. Elevated MDA levels positively correlated with TUG1 expression and inversely with GPX4 mRNA level, suggesting increased oxidative stress and possible ferroptosis-related involvement. Reduced expression of CD5 and CD34 confirmed efficient removal of somatic-cell contamination. Higher BMI was negatively correlated with sperm motility indices. Altered expression of TUG1 and GPX4 in asthenozoospermic sperm is consistent with involvement of ferroptosis-related pathways in impaired motility. These findings provide mechanistic insight into oxidative-stress-mediated sperm dysfunction and may inform future diagnostic and therapeutic strategies for male infertility.