The seminal plasma sTLR4/IL-1β ratio as an independent factor associated with sperm chromatin condensation defects

To investigate the associations between seminal plasma inflammatory biomarkers, particularly the sTLR4/IL-1β ratio, and sperm chromatin condensation deficiency (SCCD) in men undergoing fertility evaluation, and to assess its potential utility in identifying individuals at risk for SCCD.

74 men undergoing fertility evaluation were enrolled and categorized into a Normal SCCD group (SCCD ≤ 30%, n = 37) and an Impaired SCCD group (SCCD > 30%, n = 37) based on aniline blue staining. Seminal plasma levels of inflammatory markers, including HMGB1, sTLR4, IL-1β, TNF-α and oxidative stress markers, including 8-iso-PGF2α, total antioxidant capacity (T-AOC) were measured. Spearman correlation analysis, Firth's penalized logistic regression, and receiver operating characteristic (ROC) curve analysis was employed to evaluate the discriminative performance of the biomarkers and the combined score, respectively.

Univariate Firth regression analysis revealed that the sTLR4/IL-1β ratio was a factor associated with reduced risk against SCCD (OR approaching 0, 95% CI: 0.00 - 0.04, P = 0.006), while T-AOC was significantly associated with increased risk of SCCD (OR = 200.99, 95% CI: 1.52 - 38205.02, P = 0.033). Multivariable analysis confirmed that sTLR4/IL-1β remained an independent factor associated with reduced SCCD risk after adjusting for confounders (P < 0.001), whereas T-AOC was not statistically significant in the multivariable model (P = 0.472). ROC curve analysis yielded an area under the curve (AUC) of 0.786 for sTLR4/IL-1β, indicating moderate-to-good discriminative ability.

A higher seminal plasma sTLR4/IL-1β ratio is independently associated with reduced SCCD risk, suggesting that preserved immunological buffering may protect sperm chromatin integrity. The sTLR4/IL-1β ratio demonstrates moderate-to-good discriminatory ability (AUC = 0.786) and, as an exploratory finding, may serve as a potential auxiliary assessment tool in future larger validation studies.