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

Alwin A.H.A. Derijck, Godfried W. van der Heijden, Liliana Ramos, Maud Giele, Jan A.M. Kremer, Peter de Boer

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Abstract

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 γH2AX 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 γH2AX 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.

Original languageEnglish
Pages (from-to)2368-2376
Number of pages9
JournalHuman Reproduction
Volume22
Issue number9
DOIs
Publication statusPublished - Sept 2007

Keywords

  • Chromatin
  • DNA degradation
  • Double-strand DNA break
  • ICSI
  • Sperm

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