XRCC1 deficiency correlates with increased DNA damage and male infertility

Abstract

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. © 2019 Elsevier B.V.