PsA inhibits the development of bovine embryos through epigenetic and oxidative stress

Abstract

Abstract OBJECTIVE Histone deacetylases (HDACs) are the key regulators involved in the process of embryo development and tumor progression and are often dysregulated in numerous disordered cells, including tumor cells and somatic cell nuclear transfer (SCNT) embryos. Psammaplin A (PsA), a natural small-molecular therapeutic agent, is a potent histone deacetylase inhibitor (HDACi) that alters the regulation of histone. SAMPLES Approximately 2,400 bovine parthenogenetic (PA) embryos. PROCEDURES To investigate the effect of PsA on bovine preimplanted embryos, we analyzed the preimplantation development of PA embryos treated with PsA in this study. RESULTS The blastocyst formation rate of bovine PA embryos decreased sharply with an increase in concentration and duration. Furthermore, the expression of the pluripotency-related gene Nanog was decreased, and the inhibitory effects on histone deacetylases 1 (HDAC1) and DNA methylation transferase 1 (DNMT1) were observed in bovine PA embryos. The acetylation level of histone H3 lysine 9 (H3K9) was enhanced by a PsA treatment of 10 μM for 6 h, while the DNA methylation appeared unchanged. Interestingly, we also found that PsA treatment enhanced the intracellular reactive oxygen species (ROS) generation and decreased the intracellular mitochondrial membrane potential (MMP)- and superoxide dismutase 1 (SOD1)-induced oxidative stress. Our findings improve the understanding of HDAC in embryo development and provide a theoretical basis and reproduction toxicity evaluation for the application of PsA. CLINICAL RELEVANCE These results indicate that PsA inhibits the development of bovine preimplantation PA embryos, supplying data for the PsA clinical application concentration to avoid reproductive toxicity. In addition, the reproduction toxic effect of PsA may be modulated through increased oxidative stress on the bovine PA embryo, suggesting that PsA in combination with antioxidants, for example, melatonin, might be an effective clinical application strategy.