Changes in acetylation on lysine 12 of histone H4 (acH4K12) of murine oocytes during maternal aging may affect fertilization and subsequent embryo development

Objective To compare acH4K12 levels in oocytes during mouse aging and then assess how such changes might affect the developmental potential of oocytes. Design Experimental animal study. Setting State key laboratory and university research laboratory. Animal(s) Kunming white strain mice. Intervention(s) Oocytes obtained from TSA treated group or aging mouse group were fertilized and the formation of pronuclei and subsequently developmental potential in vitro or in vivo were assessed. Main Outcome Measure(s) AcH4K12 levels in oocytes were assessed using fluorescence staining, and confocal microscopy and oocyte developmental potentials were determined by in vitro or in vivo methods. Result(s) The AcH4K12 levels in oocytes statistically significantly increased during mouse aging. When histone acetylation of oocytes of young mice was artificially increased by trichostatin A (TSA) treatment, the acH4K12 levels in male and female pronuclei in fertilized oocytes showed statistically significant changes. About 38.9% of TSA-treated oocytes failed to form pronuclei or formed morphologically abnormal pronuclei 6 hours after fertilization, which statistically significantly decreased the blastocyst rate of TSA-treated oocytes when compared with the control group (41.5% vs. 60.5%). A similar reduction in blastocyst development was also observed when oocytes collected in older mice were compared with younger mice (17.3% vs. 69.4%). Conclusion(s) The AcH4K12 levels in oocytes statistically significantly increased during the aging process in mice, and such changes may affect the acetylation patterns and morphology of pronuclei during fertilization and lead to a reduction in oocyte developmental potential.