DNA damage in lymphocytes and lifestyle factors are associated with sperm DNA damage (#282)
Paternal factors that impair fertility and pregnancy success are increasingly being identified. To date, sperm DNA damage has been associated with infertility. However, there are no standardised tests to measure it and semen samples are difficult to collect. The cytokinesis-block micronucleus (CBMN) assay is a robust method to detect DNA damage in peripheral lymphocytes but it has not been used to assess human sperm. We aimed to determine if lymphocyte DNA damage measured using the CBMN assay can also identify men with sperm DNA damage, measured using the TUNEL assay.
Twenty-two eligible men were recruited for the Predicting Adverse Pregnancy Outcomes (PAPO) study. Men provided semen for standard semen analysis (WHO guidelines) and TUNEL labelling of sperm, and fasted blood samples for lymphocyte isolation and CBMN analysis. Clinical and lifestyle data were also collected. Lymphocytes were scored using established criteria, the frequency of binucleated (BN) cells with one or more micronuclei (MN) were counted, with 400 BN cells counted per duplicate culture (total 800 BN per subject). Sperm DNA damage was calculated as the percentage of TUNEL positive sperm.
Ten men had abnormal, and twelve had normal, semen parameters. Men with abnormal semen had significantly higher sperm DNA damage (P<0.001) and lymphocyte DNA damage (P=0.005) than those with normal semen. The percentage of sperm with normal morphology was inversely correlated with BMI (r=-0.671, P=0.002). There was a strong positive correlation between lymphocyte DNA damage and sperm DNA damage (r=0.725, P<0.001).
Our data suggests that sperm DNA damage is associated with peripheral lymphocyte DNA damage and these also occur in men with abnormal semen parameters. Elevated BMI associates with poor sperm morphology. In future a blood sample, rather than a semen sample, may be used to detect male genome damage that may mark impaired fertility and pregnancy success.