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XRCC1 deficiency correlates with increased DNA damage and male infertility.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis ( IF 2.3 ) Pub Date : 2019-02-13 , DOI: 10.1016/j.mrgentox.2019.01.004
Vertika Singh 1 , Sujit Kumar Mohanty 2 , Priyanka Verma 1 , Arijit Chakraborty 1 , Sameer Trivedi 3 , Singh Rajender 2 , Kiran Singh 1
Affiliation  

High fidelity DNA repair is critical to sustain the genomic integrity and quality of developing germ cells. Deficiencies in DNA repair machinery may result in increased DNA damage in germ cell leading to abnormal spermatogenesis and infertility. X-ray repair cross-complementing group 1 (XRCC1) is a testis enriched protein that plays a crucial role in the DNA base excision repair (BER) pathway. The aim of this study was to analyze the level of XRCC1 transcript and protein in infertile men and its association with DNA damage in sperm. A total of eighty infertile patients with different infertile phenotypes (Azoospermia, n = 30; Severe oligozoospermia, n = 25; Severe oligoasthenozoospermia, n = 25) and age-matched controls (normal spermatogenesis [NS], n = 15 and fertile controls, n = 10) were recruited. γ-H2 AX protein levels were analyzed to estimate the DNA damage in sperm. XRCC1 transcript levels in cases and controls were determined by qRT-PCR. XRCC1 and γ-H2 AX proteins were immunohistochemically analyzed in testicular biopsy sections obtained from NOA patients and OA controls. The determination of XRCC1 and γ-H2 AX protein levels was performed with Western blots. The results revealed reduced expression of XRCC1 mRNA and protein in infertile individuals as compared to controls (p < 0.001). γ-H2 AX levels were significantly increased in infertile cases as compared to controls, indicating increased DNA damage in infertile men. The results indicate decreased expression of the XRCC1 gene in infertile patients which may be one of the factors associated with impaired spermatogenesis and infertility.

中文翻译:

XRCC1缺乏与DNA损伤增加和男性不育有关。

高保真DNA修复对于维持发育中的生殖细胞的基因组完整性和质量至关重要。DNA修复机制的缺陷可能导致生殖细胞中DNA损伤的增加,从而导致异常的精子发生和不育。X射线修复交叉互补组1(XRCC1)是富含睾丸的蛋白质,在DNA碱基切除修复(BER)途径中起着至关重要的作用。这项研究的目的是分析不育男性中XRCC1转录和蛋白质的水平及其与精子DNA损伤的关系。共有80名具有不同不育表型的不育患者(无精子症,n = 30;严重少精子症,n = 25;严重少尿症,少精子症,n = 25)和年龄匹配的对照者(正常精子生成[NS],n = 15,以及受精对照者, n = 10)被招募。分析了γ-H2AX蛋白水平,以估计精子中的DNA损伤。通过qRT-PCR确定病例和对照中的XRCC1转录物水平。在从NOA患者和OA对照获得的睾丸活检切片中对XRCC1和γ-H2AX蛋白进行了免疫组织化学分析。XRCC1和γ-H2AX蛋白水平的测定采用蛋白质印迹法进行。结果显示,与对照组相比,不育个体中XRCC1 mRNA和蛋白的表达降低(p <0.001)。与对照组相比,不育病例中的γ-H2AX水平显着升高,表明不育男性的DNA损伤增加。结果表明,不育患者中XRCC1基因的表达降低,这可能是与精子发生和不育能力受损有关的因素之一。通过qRT-PCR确定病例和对照中的XRCC1转录物水平。在从NOA患者和OA对照获得的睾丸活检切片中对XRCC1和γ-H2AX蛋白进行了免疫组织化学分析。XRCC1和γ-H2AX蛋白水平的测定采用蛋白质印迹法进行。结果显示,与对照组相比,不育个体中XRCC1 mRNA和蛋白的表达降低(p <0.001)。与对照组相比,不育病例中的γ-H2AX水平显着升高,表明不育男性的DNA损伤增加。结果表明,不育患者中XRCC1基因的表达降低,这可能是与精子发生和不育能力受损有关的因素之一。通过qRT-PCR确定病例和对照中的XRCC1转录物水平。在从NOA患者和OA对照获得的睾丸活检切片中对XRCC1和γ-H2AX蛋白进行了免疫组织化学分析。XRCC1和γ-H2AX蛋白水平的测定采用蛋白质印迹法进行。结果显示,与对照组相比,不育个体中XRCC1 mRNA和蛋白的表达降低(p <0.001)。与对照组相比,不育病例中的γ-H2AX水平显着升高,表明不育男性的DNA损伤增加。结果表明,不育患者中XRCC1基因的表达降低,这可能是与精子发生和不育能力受损有关的因素之一。在从NOA患者和OA对照获得的睾丸活检切片中对XRCC1和γ-H2AX蛋白进行了免疫组织化学分析。XRCC1和γ-H2AX蛋白水平的测定采用蛋白质印迹法进行。结果显示,与对照组相比,不育个体中XRCC1 mRNA和蛋白的表达降低(p <0.001)。与对照组相比,不育病例中的γ-H2AX水平显着升高,表明不育男性的DNA损伤增加。结果表明,不育患者中XRCC1基因的表达降低,这可能是与精子发生和不育能力受损有关的因素之一。在从NOA患者和OA对照获得的睾丸活检切片中对XRCC1和γ-H2AX蛋白进行了免疫组织化学分析。XRCC1和γ-H2AX蛋白水平的测定采用蛋白质印迹法进行。结果显示,与对照组相比,不育个体中XRCC1 mRNA和蛋白的表达降低(p <0.001)。与对照组相比,不育病例中的γ-H2AX水平显着升高,表明不育男性的DNA损伤增加。结果表明,不育患者中XRCC1基因的表达降低,这可能是与精子发生和不育能力受损有关的因素之一。结果显示,与对照组相比,不育个体中XRCC1 mRNA和蛋白的表达降低(p <0.001)。与对照组相比,不育病例中的γ-H2AX水平显着升高,表明不育男性的DNA损伤增加。结果表明,XRCC1基因在不育患者中的表达降低,这可能是与精子发生和不育受损相关的因素之一。结果显示,与对照组相比,不育个体中XRCC1 mRNA和蛋白的表达降低(p <0.001)。与对照组相比,不育病例中的γ-H2AX水平显着升高,表明不育男性的DNA损伤增加。结果表明,不育患者中XRCC1基因的表达降低,这可能是与精子发生和不育能力受损有关的因素之一。
更新日期:2019-11-01
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