title: 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.
authors.affiliation: Klinik und Poliklinik für Urologie, Kinderurologie und Andrologie, Justus-Liebig-Universität, Giessen, Germany.
authors.forename: K
authors.identifier: 0000-0003-0964-5799
authors.initials: K
authors.lastname: Ni
authors.affiliation: Department of Andrology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: A-N
authors.initials: AN
authors.lastname: Spiess
authors.affiliation: Klinik und Poliklinik für Urologie, Kinderurologie und Andrologie, Justus-Liebig-Universität, Giessen, Germany.
authors.forename: H-C
authors.initials: HC
authors.lastname: Schuppe
authors.affiliation: Klinik und Poliklinik für Urologie, Kinderurologie und Andrologie, Justus-Liebig-Universität, Giessen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Steger
mesh_terms: D004249:DNA Damage / Q000502:physiology*; D053938:DNA Fragmentation; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011479:Protamines / Q000378:metabolism*; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D011479:Protamines
keywords: DNA damage; male infertility; protamine ratio; spermatozoa