The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta-analysis.

Abstract

Existing literature suggests evidence that protamine deficiency is related to DNA damage and male fertility. In this meta-analysis, we analyzed the relationship between the ratio of protamine-1 and protamine-2 with male fertility and the association of protamine deficiency with sperm DNA damage. Quality of available cohort studies was evaluated using the Newcastle-Ottawa Scale checklist. Summary effect estimates with 95% confidence intervals (CI) were derived using a random effects model. The effect of the protamine ratio on male fertility was analyzed in nine studies demonstrating a significantly higher value of the protamine ratio in subfertile men (n=633) when compared with controls (n=453, SMD=0.46, 95% CI 0.25-0.66, Z=4.42, p<0.00001). Both protamine mRNA (SMD=0.45, 95% CI 0.11-0.79, Z=2.63, p=0.009) and protein ratio (SMD=0.46, 95% CI 0.25-0.68, Z=4.22, p<0.0001) showed significantly increased values in subfertile patients. The association between protamine deficiency and DNA damage was analyzed in 12 studies (n=845) exhibiting a combined overall correlation coefficient (COR) of 0.53 (95% CI 0.28-0.71, Z=3.87, p<0.001). Protamine deficiency measured by CMA3 staining was significantly associated with sperm DNA damage (COR=0.71, 95% CI 0.48-0.85, Z=4.87, p<0.001), whereas the P1/P2 ratio was not (COR=0.17, 95% CI -0.16 to 0.46, Z=0.99, p=0.33). It is concluded that the protamine ratio represents a suitable biomarker for the assessment of sperm quality and protamine deficiency is closely related with sperm DNA damage.