Paternal impacts on development: identification of genomic regions vulnerable to oxidative DNA damage in human spermatozoa

AbstractSTUDY QUESTION Do all regions of the paternal genome within the gamete display equivalent vulnerability to oxidative DNA damage?SUMMARY ANSWEROxidative DNA damage is not randomly distributed in mature human spermatozoa but is instead targeted, with particular chromosomes being especially vulnerable to oxidative stress.WHAT IS KNOWN ALREADYOxidative DNA damage is frequently encountered in the spermatozoa of male infertility patients. Such lesions can influence the incidence ofde novo mutations in children, yet it remains to be established whether all regions of the sperm genome display equivalent susceptibility to attack by reactive oxygen species.STUDY DESIGN, SIZE, DURATIONHuman spermatozoa obtained from normozoospermic males (n = 8) were split into equivalent samples and subjected to either hydrogen peroxide (H2O2) treatment or vehicle controls before extraction of oxidized DNA using a modified DNA immunoprecipitation (MoDIP) protocol. Specific regions of the genome susceptible to oxidative damage were identified by next-generation sequencing and validated in the spermatozoa of normozoospermic males (n = 18) and in patients undergoing infertility evaluation (n = 14).PARTICIPANTS/MATERIALS, SETTING, METHODSHuman spermatozoa were obtained from normozoospermic males and divided into two identical samples prior to being incubated with either H2O2 (5  mm, 1  h) to elicit oxidative stress or an equal volume of vehicle (untreated controls). Alternatively, spe...
Source: Human Reproduction - Category: Reproduction Medicine Source Type: research