The association between mutations in ubiquitin-specific protease 26 (USP26) and male infertility: a systematic review and meta-analysis

Abstract

During recent decades, the association between mutations in ubiquitin-specific protease 26 (USP26) and male infertility remains doubtful. We conducted this meta-analysis to evaluate the association between mutations in USP26 and male infertility according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. It was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021225251). PubMed, Web of Science, and Scopus were systematically searched for comparative clinical studies, which were written in English and provided eligible data. Studies were included when they compared USP26 mutations in azoospermic, oligozoospermic, and asthenozoospermic patients with controls with normal sperm parameter values or whose partners had experienced spontaneous pregnancy. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated with random effect models. Overall, twelve studies with 3927 infertility patients and 4648 healthy controls were included. The association between overall USP26 mutations and infertility was not significant (OR = 1.60, 95% CI: 0.51-5.01). For specific mutations, the pooled ORs were 1.65 (95% CI: 1.02-2.69) for cluster mutation (including 370-371insACA, 494T>C, and 1423C>T), 1.80 (95% CI: 0.35-9.15) for c.576G>A, 1.43 (95% CI: 0.79-2.56) for c.1090C>T, and 3.59 (95% CI: 2.30-5.59) for c.1737G>A. Our results suggest that several mutations (cluster mutation, c.1737G>A) may play roles in male infertility, while others (c.576G>A and c.1090C>T) do not show notable associations with male infertility. More high-quality clinical researches are needed for validation.

Keywords: azoospermia; haplotype; male infertility; mutation; ubiquitin-specific protease 26.

Figure 1

Flow diagram of the included study in this meta-analysis.

Figure 2

Forest plot of the association between overall mutations of ubiquitin-specific protease 26 (USP26) and male infertility. CI: confidence interval; df: degrees of freedom; M–H: Mantel–Haenszel.

Figure 3

Forest plots of the association between variants of ubiquitin-specific protease 26 (USP26) and (a) male infertility and (b) cluster mutation of USP26 (c.576G>A). CI: confidence interval; df: degrees of freedom; M–H: Mantel–Haenszel.

Figure 4

Forest plots of the association between variants of ubiquitin-specific protease 26 (USP26) and male infertility: (a) c.1090C>T, (b) c.1737G>A. CI: confidence interval; df: degrees of freedom; M–H: Mantel–Haenszel.