Repair of oxidative DNA damage within the zygote is critical for production of viable embryos and healthy offspring. Although the sperm cell does not have the capacity to repair oxidative lesions within its DNA prior to fertilization, recent research has identified that the first enzyme in the base excision repair (BER) pathway, Oxoguanine Glycosylase (OGG1), is present and functional within the human spermatozoon¹. The current study has used a mouse model to investigate a potential role for sperm-derived OGG1 in 8-hydroxyguanosine (8OHdG) repair post-fertilization; specifically prior to S-phase of mitosis in the zygote.
We have identified that, as in the human spermatozoon, a truncated BER pathway exists within the murine sperm cell. Interestingly, whilst immunocytochemistry and western blot analyses revealed expression of OGG1, but not the endonuclease enzyme Apurinic/Apyrimidinic Endonuclease (APE1) within the spermatozoon; the oocyte exhibited surprisingly low levels of OGG1, but high levels of APE1 expression, suggesting that co-operation between gametes may be required for efficient 8OHdG repair post-fertilization. Indeed, repair of 8OHdG was accelerated following fertilization, with zygotes exhibiting significantly elevated levels of 8OHdG excision and release into the extracellular space (detected by an ELISA assay) (P<0.05) and significantly reduced levels of intracellular 8OHdG (P<0.05) when compared to unfertilized oocytes. Despite this, utilization of OGG1-deficient sperm from the senescence-accelerated mouse prone 8² (SAMP8) revealed that an absence of sperm-derived OGG1 did not impair 8OHdG repair nor developmental capacity within the zygote. Rather, the post-fertilization acceleration of 8OHdG repair appeared to be maternally derived, as this phenomenon was also identified in artificially-activated parthenotes (P<0.01). Although sperm-derived OGG1 does not appear to actively contribute to 8OHdG repair within the zygote, the presence of this enzyme within sperm chromatin is potentially important for initiation of DNA repair processes prior to fertilization that can only be completed upon meeting with the oocyte.