Motile human normozoospermic and oligozoospermic semen samples show a difference in double-strand DNA break incidence

BACKGROUND: Among ICSI children de novo structural chromosome aberrations of male descent are increased. Misrepair of double-strand DNA breaks (DSBs) is a prerequisite for such aberrations to occur. To date, no absolute assessment of the number of DSBs in human sperm nuclei after gamete fusion has been described. METHODS: Using man-mouse heterologous ICSI and gamma H2AX immunofluorescent staining, capable of detecting a single DSB, the number of lesions in ICSI selected sperm from normozoospermic men (n = 2) and oligozoospermic patients (n = 3) was quantified. A comparison with a subfertile male mouse model (n = 5) has been made. In addition, the fate of morphologically normal ejaculated immotile sperm after ICSI was examined. RESULTS: A significant increase in the fraction of sperm cells bearing DSBs was found in oligozoospermic semen compared with that from normozoospermic men (P < 0.01). The majority of morphologically normal immotile human sperm showed excess gamma H2AX staining and nuclear disintegration. However, some had a non-deviant DSB pattern. CONCLUSIONS: The increased fraction of DSB-positive sperm in both human and mouse oligozoospermic semen is adding to the surmise that semen from oligozoospermic patients has a reduced chromatin quality, causally related to reduced preimplantation embryo development. The use of ejaculated immotile sperm for in vitro reproduction is debatable due to sperm DNA degradation.