Early embryonic development in mammals is a sophisticated process that is activated by the fertilization of an oocyte by a mature spermatozoon. After fertilization, the oocyte completes asymmetric meiotic division and develop into a zygote. The zygote subsequently undergoes symmetric mitosis division and ultimately develops to the blastocyst stage [1]. Any error in this process may lead to implantation failure and fetal defects, leading to early pregnancy loss [2].

Lysine acetyltransferase 8 (KAT8), also called MOF (“males absent on the first”), is a member of the MYST family of histone acetyltransferases (HATs). KAT8 is initially identified as a component of the male-specific lethal (MSL) complex, which is involved in the dose compensation [3]. Meantime, KAT8 is also a constituent of the nonspecific lethal (NSL) complex, which is responsible for acetylating lysine 16 on histone H4 (H4K16) [4]. Previous data have verified that KAT8 activity is connected to a wide range of cellular processes, including DNA damage response [5], autophagy [6], cell cycle progression [7], and transcriptional regulation [8]. Kat8 knockdown inhibits Bcl-2-associated X protein (BAX) and p53-upregulated modulator of apoptosis (PUMA) transcriptional activation [9], and KAT8 leads to meiotic sex chromosome inactivation by facilitating the expansion of serine-139 phosphorylation of H2AX (γH2AX) [10]. Furthermore, Kat8-deficient embryonic stem cells lose their differentiation potential, showing changes in the morphology and gene expression of essential transcription factors [11]; and Kat8 depletion also results in the loss of epithelial cell features [12].

Although Kat8-null mice exhibit early embryonic lethality [13], a role for KAT8 in early embryonic development remains arcane. In the present study, we investigated KAT8 function in the development of in vitro cultured preimplantation embryos, and we found that Kat8-OE compromised the developmental potential of mouse embryos. Kat8-OE induced increase of oxidative stress likely through affecting expression of critical genes related to mitochondrial respiratory chain and antioxidation pathways. Meanwhile, Kat8-OE led to abnormal spindle/chromosome assembly by disrupting histone modification. Our findings indicated that KAT8 played a key role in the regulation of early embryonic development in mice.