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Shiv Basant Kumar, Bhavna Chawla, Rachna Seth, Surabhi Gautam, Rima Dada; Loss of Paternal Sperm DNA integrity in Non- familial Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6440.
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The contribution of paternal genome to offspring may depend on sperm DNA integrity. Sperm are vulnerable to oxidative damage due to minimal cytosolic anti-oxidants. Oxidative stress damages all biomolecules including nuclear and mitochondrial DNA.This study was planned with an aim to analyze the sperm DNA quality and effect of paternal life style as a possible etiological factor for non- familial Retinoblastoma (Rb) in children.
The study was approved by institutional ethical committee. A total of 43 fathers of retinoblastoma cases (Non-familial) and 50 males as control were recruited for the study. Semen samples were collected from the fathers of Rb patients (diagnosed within the first 2 years of age) and were analyzed for semen parameters. Biological markers for Sperm DNA damage such as DNA Fragmentation Assay (DFI) by SCSA,8-hydroxy-2'-deoxyguanosine (8-OHdG) by ELISA, Telomere length by Real time PCR and Reactive Oxygen Species (ROS) levels by Chemiluminiscence assay were measured. Logistic binary regression was used to compute the odds ratios (OR) for Rb.
Seminal mean ROS levels were significantly higher (36.086±1.83 vs 20.51±2.71 RLU/s/million; p=0.079) in cases as compared to controls. There was a significant increase in mean DFI levels (31.50±6.67 vs.21.9±9.4; p<0.001) in cases as compared to controls. The 8-OHdG level was significantly higher in cases (66.02±2.91 vs. 23.10±2.71 pg/mL; p<0.01) as compared to controls. Among the cases, an increased 8-OHdG level was observed in smokers (75.5±6.35 pg/mL) as compared to non- smokers (55.3±4.39 pg/mL;p=0.072). The relative sperm mean telomere length (T/S) of cases was shorter as compared to controls (0.35 ± 0.021 vs 0.38 ± 0.027; p =0.459). The observed OR for smoker was 10.0(2.9-34.45; p<0.001)95%CI while for cases with exposure to pesticides and alcohol users the OR was 3.5(1.01-12.16; p=0.037; 95%CI) and 7.292(2.13-24.92; p<0.001) respectively.
Oxidative damage leads to accumulation of mutagenic bases and shortening of telomeres. The accumulation of sperm DNA damage may contribute to the development of non- familial Rb as the presence of mutagenic base in sperms may predispose in the fetus to develop mutations. Smoking and increased alcohol intake adversely affects DNA quality and paternal lifestyle may be a possible etiological factor in the development of non-familial Rb,life style interventions can significantly improve DNA health.
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