Oxidative DNA damage in mouse sperm chromosomes: Size matters.
Normal embryo and foetal development as well as the health of the progeny are mostly dependent on gamete nuclear integrity. In the present study, in order to characterize more precisely oxidative DNA damage in mouse sperm we used two mouse models that display high levels of sperm oxidative DNA damage, a common alteration encountered both in in vivo and in vitro reproduction. Immunoprecipitation of oxidized sperm DNA coupled to deep sequencing showed that mouse chromosomes may be largely affected by oxidative alterations. We show that the vulnerability of chromosomes to oxidative attack inversely correlated with their size and was not linked to their GC richness. It was neither correlated with the chromosome content in persisting nucleosomes nor associated with methylated sequences. A strong correlation was found between oxidized sequences and sequences rich in short interspersed repeat elements (SINEs). Chromosome position in the sperm nucleus as revealed by fluorescent in situ hybridization appears to be a confounder. These data map for the first time fragile mouse sperm chromosomal regions when facing oxidative damage that may challenge the repair mechanisms of the oocyte post-fertilization.
GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, BP80006, 63171 Aubière cedex, France.
Ayhan
A
Kocer
GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, BP80006, 63171 Aubière cedex, France.
Joelle
J
Henry-Berger
GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, BP80006, 63171 Aubière cedex, France.
Anais
A
Noblanc
GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, BP80006, 63171 Aubière cedex, France.
Alexandre
A
Champroux
GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, BP80006, 63171 Aubière cedex, France.
Romain
R
Pogorelcnik
GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, BP80006, 63171 Aubière cedex, France.
Rachel
R
Guiton
GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, BP80006, 63171 Aubière cedex, France; CHU Estaing, Assistance Médicale à la Procréation, Clermont-Ferrand, France.
Laurent
L
Janny
GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, BP80006, 63171 Aubière cedex, France; CHU Estaing, Assistance Médicale à la Procréation, Clermont-Ferrand, France.
Hanae
H
Pons-Rejraji
GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, BP80006, 63171 Aubière cedex, France.
Fabrice
F
Saez
Center for Molecular Medicine & Genetics, Department of Obstetrics & Gynecology, Wayne State University, Detroit, MI 48201, USA.
Graham D
GD
Johnson
Center for Molecular Medicine & Genetics, Department of Obstetrics & Gynecology, Wayne State University, Detroit, MI 48201, USA.
Stephen A
SA
Krawetz
Centro ANDROGEN, La Coruña, Spain; Harvard Medical School, Boston, MA 02115, USA.
Juan G
JG
Alvarez
Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, Australia.
R John
RJ
Aitken
GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, BP80006, 63171 Aubière cedex, France. Electronic address: joel.drevet@univ-bpclermont.fr.
Joël R
JR
Drevet
D000818:Animals; D002467:Cell Nucleus / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics*; D004249:DNA Damage; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000235:genetics*; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology*
8-Hydroxy-2′-deoxyguanosine (8-OHdG); Mutational risk; Nuclear organization; Oxidative stress; Sperm DNA integrity