title: DNA oxidative damage in mammalian spermatozoa: where and why is the male nucleus affected?
abstract: Gamete DNA integrity is one key parameter conditioning reproductive success as well as the quality of life for the offspring. In particular, damage to the male nucleus can have profound negative effects on the outcome of fertilization. Because of the absence of repair activity of the quiescent mature spermatozoa it is easily subjected to nuclear damage, of which oxidative damage is by far the most prominent. In relation to the organization of the mammalian sperm nucleus we show here that one can correlate the nuclear regions of lower compaction with areas preferentially showing oxidative damage. More precisely, we show that oxidative DNA damage targets primarily histone-rich and nuclear matrix-attached domains located in the peripheral and basal regions of the mouse sperm nucleus. These particular sperm DNA domains were recently shown to be enriched in genes of paramount importance in postfertilization DNA replication events and in the onset of the embryonic developmental program. We propose that monitoring of sperm DNA oxidation using the type of assay presented here should be considered in clinical practice when one wants to estimate the integrity of the paternal nucleus along with more classical assays that essentially analyze DNA fragmentation and nucleus compaction.
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France.
authors: Anais
authors: A
authors: Noblanc
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France.
authors: Christelle
authors: C
authors: Damon-Soubeyrand
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France.
authors: Bouchta
authors: B
authors: Karrich
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France.
authors: Joelle
authors: J
authors: Henry-Berger
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France.
authors: Rémi
authors: R
authors: Cadet
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France.
authors: Fabrice
authors: F
authors: Saez
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France.
authors: Rachel
authors: R
authors: Guiton
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France; CHU Estaing, Assistance Médicale à la Procréation, Clermont-Ferrand, France.
authors: Laurent
authors: L
authors: Janny
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France; CHU Estaing, Assistance Médicale à la Procréation, Clermont-Ferrand, France.
authors: Hanae
authors: H
authors: Pons-Rejraji
authors: Centro Androgen, La Coruña, Spain; Harvard Medical School, Boston, MA 02115, USA.
authors: Juan G
authors: JG
authors: Alvarez
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France. Electronic address: joel.drevet@univ-bpclermont.fr.
authors: Joël R
authors: JR
authors: Drevet
authors: Genetic Reproduction and Development, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 Aubière Cedex, France.
authors: Ayhan
authors: A
authors: Kocer
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000473:pathology*; D004249:DNA Damage; D005455:Fluorescent Antibody Technique / Q000379:methods; D006657:Histones / Q000235:genetics*; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D015530:Nuclear Matrix / Q000473:pathology*; D018384:Oxidative Stress / Q000235:genetics*; D013094:Spermatozoa / Q000473:pathology*
chemical_list: D006657:Histones
keywords: Free radicals; Paternal DNA integrity; Sperm nuclear organization