title: Paternal DNA damage resulting from various sperm treatments persists after fertilization and is similar before and after DNA replication.
abstract: In spite of its highly condensed state, sperm DNA is vulnerable to damage  that can originate from oxidative stress, the activity of sperm-specific  nucleases, or both. After fertilization, in the oocyte, paternal chromatin  undergoes dramatic changes, and during this extensive remodeling, it can be  both repaired and degraded, and these processes can be linked to DNA  synthesis. Here, we analyzed sperm response to damage-inducing treatments both  before and after fertilization and before or after zygotic DNA replication.  Epididymal mouse spermatozoa were either frozen without cryoprotection (FT) or  treated with detergent Triton X-100 coupled with dithiothreitol (TX+DTT) to  induce DNA damage. Fresh, untreated sperm served as control. Immediately after  preparation, spermatozoa from 3 groups were taken for comet assay, or for  intracytoplasmic sperm injection into prometaphase I oocytes to visualize  prematurely condensed single-chromatid chromosomes, or into mature metaphase  II oocytes to visualize chromosomes after DNA replication. Comet assay  revealed increased DNA fragmentation in treated sperm when compared with  control, with FT sperm more severely affected. Chromosome analysis  demonstrated paternal DNA damage in oocytes injected with treated, but not  with fresh, sperm, with FT and TX+DTT groups now yielding similar damage.  There were no differences in the incidence of abnormal paternal karyoplates  before and after DNA synthesis in all examined groups. This study provides  evidence that subjecting sperm to DNA damage-inducing treatments results  in degradation of highly condensed sperm chromatin when it is still packed  within the sperm head, and that this DNA damage persists after fertilization.  The difference in DNA damage in sperm subjected to 2 treatments was  ameliorated in the fertilized oocytes, suggesting that some chromatin repair  might have occurred. This process, however, was independent of DNA synthesis  and took place during oocyte maturation.
authors.affiliation: Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96822, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Riel
authors.forename: Monika A
authors.initials: MA
authors.lastname: Ward
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly; D020552:Comet Assay; D015925:Cryopreservation; D004249:DNA Damage; D053938:DNA Fragmentation; D004260:DNA Repair; D004261:DNA Replication; D004229:Dithiothreitol / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D017830:Octoxynol / Q000633:toxicity*; D009865:Oocytes / Q000502:physiology; D020554:Sperm Injections, Intracytoplasmic; D013084:Sperm-Ovum Interactions; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology; D015053:Zygote / Q000502:physiology
chemical_list: D017830:Octoxynol; D004229:Dithiothreitol