Sperm Chromatin Structure Components Are Differentially Repaired in Cancer Survivors

Abstract

Chemotherapy is often associated with male infertility. Our aim was to determine the effect of chemotherapy on sperm chromatin quality in cancer survivors. Sixteen men with advanced testicular cancer and 15 with Hodgkin lymphoma requiring chemotherapy were compared with 11 community volunteers. Eleven idiopathic infertile men with abnormal sperm chromatin were included as a positive control group. Semen analysis and sperm chromatin quality were determined prechemotherapy and at 6, 18, and 24 months posttreatment. DNA damage was determined by the sperm chromatin structure assay (SCSA). The level of DNA compaction was assayed by determining high DNA stainability (HDS, SCSA), the percentage of free thiols (monobromobimane-labeling assay), and the level of protamination (chromomycin A3-labeling assay). Sperm concentration and motility were dramatically decreased in cancer patients 6-18 months after chemotherapy compared with community volunteers but were not statistically different from community volunteers at 24 months posttreatment. High levels of DNA damage were observed prechemotherapy, with a tendency to remain high during the 24-month posttreatment period in testicular cancer patients; low DNA compaction (HDS, SCSA) persisted in testicular cancer patients 24 months postchemotherapy. Low levels of sperm DNA compaction were observed in cancer patients compared with community volunteers and infertile men. Sperm monobromobimane and chromomycin A3 labeling in cancer patients were similar to those from community volunteers by 18 months after treatment. Chemotherapy-induced damage to components of the sperm chromatin structure was repaired differentially over time. However, significant sperm DNA damage and low DNA compaction remained up to 24 months posttreatment. The assessment of complementary aspects of sperm chromatin quality is necessary to evaluate sperm samples in cancer survivors.