Seminal-Plasma Ferroptosis Markers (GPX4 and ACSL4) and Their Relation to Sperm DNA Fragmentation in Asthenozoospermic Iraqi Men

Durar Kamil Jabbar

doi:10.70604/jmtbas.v3i2.231

Authors

Durar Kamil Jabbar Department of Basic Sciences, College of Dentistry, University of Al-Qadisiyah, Al-Diwaniyah, Iraq.

Abstract

Background: Ferroptosis is an iron-dependent cell death driven by peroxidation of membrane phospholipids. Sperm membranes are rich in polyunsaturated lipids, which makes them a likely target. Glutathione peroxidase 4 (GPX4) blocks this process and acyl-CoA synthetase long-chain family member 4 (ACSL4) feeds it. Neither has been studied in the seminal plasma of Iraqi men. Methods: This case–control study enrolled 60 men with isolated asthenozoospermia (progressive motility < 30%) and 60 normozoospermic controls at the Fertility Centre, Al-Diwaniyah, Iraq. Semen was examined by the WHO 2021 manual, seminal-plasma GPX4 and ACSL4 were measured by sandwich ELISA, and the sperm DNA fragmentation index (DFI) was read with the sperm chromatin dispersion test. Results: Compared with controls, asthenozoospermic men had significantly lower GPX4 (5.18 ± 1.76 vs 8.52 ± 2.34 ng/mL; p < 0.001) and significantly higher ACSL4 (6.37 ± 1.88 vs 3.84 ± 1.25 ng/mL; p < 0.001). The ACSL4/GPX4 ratio was 1.36 ± 0.51 vs 0.48 ± 0.20 (p < 0.001), and DFI was 32.7 ± 10.4% vs 15.3 ± 5.8% (p < 0.001). Within the case group, DFI correlated with GPX4 (r = −0.44; Bonferroni p = 0.0008) and with ACSL4 (r = 0.41; Bonferroni p = 0.002). The ratio separated cases from controls with an AUC of 0.88 (95% CI 0.82, 0.93). Conclusion: A disturbed seminal ferroptosis balance, marked by lower GPX4 and higher ACSL4, tracked with greater sperm DNA damage in asthenozoospermic men. The ACSL4/GPX4 ratio deserves further evaluation as a simple, non-invasive add-on to routine semen work-up.

Keywords:

Ferroptosis, Glutathione peroxidase 4, ACSL4, Seminal plasma, Sperm DNA fragmentation, Asthenozoospermia

DOI

https://doi.org/10.70604/jmtbas.v3i2.231

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