title: Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.
abstract: Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (<1 hr) P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis.
authors.forename: Victoria
authors.initials: V
authors.lastname: Burruel
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis.
authors.forename: Katie
authors.initials: K
authors.lastname: Klooster
authors.affiliation: Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Barker
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Stanford University.
authors.forename: Renee Reijo
authors.initials: RR
authors.lastname: Pera
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis.
authors.forename: Stuart
authors.initials: S
authors.lastname: Meyers
mesh_terms: D000782:Aneuploidy; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008938:Mitosis / Q000235:genetics*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology