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The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta‐analysis
Author(s) -
Ni K.,
Spiess A.N.,
Schuppe H.C.,
Steger K.
Publication year - 2016
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12216
Subject(s) - protamine , sperm , fertility , andrology , confidence interval , medicine , biology , population , heparin , environmental health
Summary 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 CMA 3 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.