Oocyte development involves extensive transcriptional and epigenetic changes in order to eventually produce a mature egg competent for fertilisation. Key to this process is the avoidance of apoptosis, but how anti-apoptotic genes are regulated during oogenesis remains largely undefined. Now, on p. 2165, Qinghua Shi and colleagues show that genetic deletion of histone acetyltransferase KAT8 specifically in mouse oocytes at the primordial follicle stage causes the defective development of follicles from the secondary follicle stage, which subsequently leads to female infertility. The authors observe significantly increased reactive oxygen species (ROS) levels in the mutant oocytes, coincident with the downregulation of several antioxidant genes and show via chromatin immunoprecipitation assays that KAT8 regulates antioxidant gene expression by direct binding to promoter regions. Importantly, the authors are able to rescue the defects of folliculogenesis after Kat8 deletion in oocytes by antioxidant administration in mice. This study demonstrates for the first time that KAT8 represses ROS levels in oocytes by promoting the expression of antioxidant genes at the transcriptional level, and provides insight into the epigenetic regulation of female fertility.