Aim: To study the incidence of single nucleotide polymorphisms in ubiquitin-specific protease 26 (USP26) gene and its involvement in idiopathic male infertility in China. Methods: Routine semen analysis was perfor...Aim: To study the incidence of single nucleotide polymorphisms in ubiquitin-specific protease 26 (USP26) gene and its involvement in idiopathic male infertility in China. Methods: Routine semen analysis was performed. Infertility factors such as immunological, infectious and biochemical disorders were examined to select patients with idiopathic infertility. DNA was isolated from peripheral blood of the selected patients and control population, which were examined for mutations using polymerase chain reaction-single strand conformation polymorphism analysis. Furthermore, nucleotide sequences were sequenced in some patients and controls. Results: Of 41 infertile men, 9 (22.0%, P = 0.01) had changes in USP26 gene on the X chromosome. A compound mutation (364insACA; 460G→A) was detected in 8 patients (19.5%, P = 0.01) and a 1044T→A substitution was found in 1 patient (2.4%, P 〉 0.05). All three variations led to changes in the coding amino acids. Two substitutions predict some changes: 460G→ A changes a valine into an isoleucine, and 1044T → A substitutes a leucine for a phenylalanine. Another insertion of three nucleotides ACA causes an insertion of threonine. No other changes were found in the remaining patients and fertile controls. Conclusion: The USP26 gene might be of importance in male reproduction. Mutations in this gene might be associated with male infertility, and might negatively affect testicular function. Further research on this issue is in progress.展开更多
Whether the 370-371insACA, 494T〉C, and 1423C〉T haplotype in ubiquitin-specific protease 26 (USP26) gene is associated with male infertility is controversial. To clarify this issue, we conducted a meta-analysis bas...Whether the 370-371insACA, 494T〉C, and 1423C〉T haplotype in ubiquitin-specific protease 26 (USP26) gene is associated with male infertility is controversial. To clarify this issue, we conducted a meta-analysis based on the most recent studies. Eligible studies were screened by using PubMed and Embase. Pooled odd ratio (OR) with 95% confidence interval (CI) was calculated with fixed effect models. Ten studies with 1603 patients and 2505 controls were included, Overall, the results indicated that there was an association between the haplotype and male infertile risk (OR = 1.74, 95% CI: 1.09-2.77). The OR calculated based on the five studies in Asia and three in Europe was 1.96 (95% CI: 1,05-3.67) and 1.54 (95% Ch 0.75-3.16) respectively, however, the OR was 0.86 (95% Ch 0.05-15,29) based on the two investigations in America. In addition, the data from the patients with azoospermia (AZO) showed an increased pooled OR of 2.35 (95% Cl: 1.22-4.50). In contrast, the studies with oligoasthenoteratozoospermia (OAT) exhibited that the pooled OR was 0,97 (95% Ch 0.43-2.16). Our analyses indicate that there is an association of alteration in USP26 with male infertility, especially in AZO and Asian population.展开更多
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 US...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.展开更多
Deubiquitinating enzymes (DUBs) play an important role in ubiquitin-dependent processes as negative regulators of protein ubiquitination. Ubiquitin-specific protease 26 (USP26) is a member of this family. The expr...Deubiquitinating enzymes (DUBs) play an important role in ubiquitin-dependent processes as negative regulators of protein ubiquitination. Ubiquitin-specific protease 26 (USP26) is a member of this family. The expression of Usp26 in mammalian testis and in other tissues has yet to be fully elucidated. To study the expression of Usp26 mRNA and protein in various murine tissues, reverse transcription (RT)-PCR and immunohistochemistry analyses were carried out. The RT-PCR analysis showed that the Usp26 transcript was expressed in all of the tested tissues. USP26 protein localization was examined by immunohistochemistry, and it was shown that USP26 was not detectable at 20 days postpartum, with the expression restricted to the cytoplasm of condensing spermatids (steps 9-16), Leydig cells and nerve fibers in the brain. In addition, the USP26 protein was detected at moderate levels in myocardial ceils, the corpus of epidydimis, epithelium of the renal tubules and the seminal gland of postnatal day 35 mice. Its spatial and temporal expression pattern suggests that Usp26 may play an important role in development or function of the testis and brain. Further research into these possibilities is in progress.展开更多
目的泛素特异蛋白酶26基因(ubiquitin specific protease 26,USP26)序列改变是否影响精子发生还存在争议。文中对精子发生障碍患者进行USP26基因序列分析,以检验USP26基因序列改变在不育男性患者中的分布,并分析与精子发生障碍之间的关...目的泛素特异蛋白酶26基因(ubiquitin specific protease 26,USP26)序列改变是否影响精子发生还存在争议。文中对精子发生障碍患者进行USP26基因序列分析,以检验USP26基因序列改变在不育男性患者中的分布,并分析与精子发生障碍之间的关系。方法在排除染色体畸变和Y染色体微缺失的基础上,对156例无精子症和非梗阻性少精子症不育患者和86例正常生育男性对照者进行了USP26基因测序。结果USP26基因序列存在6种改变,其中g.508G>A,p.G170R仅在少精子组中发现,以前未见报道。除同义突变g.576G>A外,其他序列改变在不育组和生育组中的分布没有显著差异。结论USP26基因序列改变可能并不直接影响精子发生。展开更多
基金Acknowledgment We thank the laboratory, clinical and paramedical staff of the center of Reproductive Medicine, and the Departmerit of Forensic Medicine, Pathology for their assistance. We especially thank Dr Sheng-Bin Li for practical support. This study was supported by National Natural Science Foundation of China (No. 30471735) and Science & Technique Research Intensive Project of Education Ministry of China (No.105157) and Sci-Technical Development Project of Shaanxi Province, China (2005K15-G2, 2006K15-G4).
文摘Aim: To study the incidence of single nucleotide polymorphisms in ubiquitin-specific protease 26 (USP26) gene and its involvement in idiopathic male infertility in China. Methods: Routine semen analysis was performed. Infertility factors such as immunological, infectious and biochemical disorders were examined to select patients with idiopathic infertility. DNA was isolated from peripheral blood of the selected patients and control population, which were examined for mutations using polymerase chain reaction-single strand conformation polymorphism analysis. Furthermore, nucleotide sequences were sequenced in some patients and controls. Results: Of 41 infertile men, 9 (22.0%, P = 0.01) had changes in USP26 gene on the X chromosome. A compound mutation (364insACA; 460G→A) was detected in 8 patients (19.5%, P = 0.01) and a 1044T→A substitution was found in 1 patient (2.4%, P 〉 0.05). All three variations led to changes in the coding amino acids. Two substitutions predict some changes: 460G→ A changes a valine into an isoleucine, and 1044T → A substitutes a leucine for a phenylalanine. Another insertion of three nucleotides ACA causes an insertion of threonine. No other changes were found in the remaining patients and fertile controls. Conclusion: The USP26 gene might be of importance in male reproduction. Mutations in this gene might be associated with male infertility, and might negatively affect testicular function. Further research on this issue is in progress.
文摘Whether the 370-371insACA, 494T〉C, and 1423C〉T haplotype in ubiquitin-specific protease 26 (USP26) gene is associated with male infertility is controversial. To clarify this issue, we conducted a meta-analysis based on the most recent studies. Eligible studies were screened by using PubMed and Embase. Pooled odd ratio (OR) with 95% confidence interval (CI) was calculated with fixed effect models. Ten studies with 1603 patients and 2505 controls were included, Overall, the results indicated that there was an association between the haplotype and male infertile risk (OR = 1.74, 95% CI: 1.09-2.77). The OR calculated based on the five studies in Asia and three in Europe was 1.96 (95% CI: 1,05-3.67) and 1.54 (95% Ch 0.75-3.16) respectively, however, the OR was 0.86 (95% Ch 0.05-15,29) based on the two investigations in America. In addition, the data from the patients with azoospermia (AZO) showed an increased pooled OR of 2.35 (95% Cl: 1.22-4.50). In contrast, the studies with oligoasthenoteratozoospermia (OAT) exhibited that the pooled OR was 0,97 (95% Ch 0.43-2.16). Our analyses indicate that there is an association of alteration in USP26 with male infertility, especially in AZO and Asian population.
基金funded by National Natural Science Foundation of China(grant No.82072838)Tongji Outstanding Young Researcher Funding(grant No.2020YQ13)Huazhong University of Science and Technology(grant No.2019kfyXKJC06).
文摘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.
基金Acknowledgment We thank the laboratory, clinical and paramedical staff of the center of Reproductive Medicine, and the Department of Pathology for their assistance. This study was supported by the National Natural Science Foundation of China (30471735 and 30700654) and the Sci-Technical Development Project of Shanxi Province, China (2006K 15-G4).
文摘Deubiquitinating enzymes (DUBs) play an important role in ubiquitin-dependent processes as negative regulators of protein ubiquitination. Ubiquitin-specific protease 26 (USP26) is a member of this family. The expression of Usp26 in mammalian testis and in other tissues has yet to be fully elucidated. To study the expression of Usp26 mRNA and protein in various murine tissues, reverse transcription (RT)-PCR and immunohistochemistry analyses were carried out. The RT-PCR analysis showed that the Usp26 transcript was expressed in all of the tested tissues. USP26 protein localization was examined by immunohistochemistry, and it was shown that USP26 was not detectable at 20 days postpartum, with the expression restricted to the cytoplasm of condensing spermatids (steps 9-16), Leydig cells and nerve fibers in the brain. In addition, the USP26 protein was detected at moderate levels in myocardial ceils, the corpus of epidydimis, epithelium of the renal tubules and the seminal gland of postnatal day 35 mice. Its spatial and temporal expression pattern suggests that Usp26 may play an important role in development or function of the testis and brain. Further research into these possibilities is in progress.
文摘目的泛素特异蛋白酶26基因(ubiquitin specific protease 26,USP26)序列改变是否影响精子发生还存在争议。文中对精子发生障碍患者进行USP26基因序列分析,以检验USP26基因序列改变在不育男性患者中的分布,并分析与精子发生障碍之间的关系。方法在排除染色体畸变和Y染色体微缺失的基础上,对156例无精子症和非梗阻性少精子症不育患者和86例正常生育男性对照者进行了USP26基因测序。结果USP26基因序列存在6种改变,其中g.508G>A,p.G170R仅在少精子组中发现,以前未见报道。除同义突变g.576G>A外,其他序列改变在不育组和生育组中的分布没有显著差异。结论USP26基因序列改变可能并不直接影响精子发生。