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K (Lysine) Acetyltransferase 8 (KAT8), an important component of the X chromosome dosage compensation system in Drosophila, regulates gene activity by acetylating histone H4 preferentially at lysine 16. To explore the function of Kat8 during mouse oocyte development, we crossed Kat8flox\/floxmice with Gdf9-Cre mice to specifically delete Kat8 in oocytes. Oocyte Kat8 deletion resulted in female infertility with follicle development failure in the secondary and preantral follicle stages. RNA-seq analysis revealed that Kat8 deficiency in oocytes resulted in significant down-regulation of antioxidant genes with a subsequent increase in reactive oxygen species. Intraperitoneal injection of the antioxidant N-acetylcysteine rescued defective follicle and oocyte development resulting from Kat8 deficiency. Chromatin immunoprecipitation assay indicated that KAT8 regulates antioxidant gene expression by direct binding to promoter regions. 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