Pioglitazone Mediated Reduction in Oxidative Stress and Alteration in Level of PPARγ, NRF2 and Antioxidant Enzyme Genes in Mouse Preimplantation Embryo during Maternal to Zygotic Transition
Pioglitazone Mediated Reduction in Oxidative Stress and Alteration in Level of PPARγ, NRF2 and Antioxidant Enzyme Genes in Mouse Preimplantation Embryo during Maternal to Zygotic Transition
Xu Lijie, Obaid Ullah, Liu Haixing, Ihsan Ali, Zhongshu Li* and Nan-Zhu Fang*
ABSTRACT
Excessive accumulation of reactive oxygen species (ROS) is one of the reasons for the slow growth of mammalian preimplantation embryos. Peroxisome proliferators-activated receptor gamma (PPARγ) functions in the nuclear regulatory factor 2 (Nrf2) antioxidant pathways by binding to the promoters of antioxidant genes and regulates the expression of genes that associate with NADPH oxidase. To understand the role of PPARγ in the development of early embryos and define the mechanism responsible for the arrest in development during the maternal-to-zygotic transition (MZT), we used an embryo model of oxidative damage by H2O2. We found that H2O2 exposure significantly decreased embryo development, increased the intracellular ROS level, and upregulated the expression levels of the NADPH oxidase genes NOX2, DUOX1, and NOXA1. By contrast, embryo treatment with pioglitazone after H2O2 exposure promote embryo development, significantly decreased the ROS level, downregulates the expression levels of NOX2, DUOX1, and NOXA1, and upregulated the expression levels of PPARγ, Nrf2, and the antioxidant enzyme genes GPx3, GPx4, SOD1, SOD2, and SOD3. In conclusion, pioglitazone can reduce intracellular oxidative stress during in vitro development by promoting the expression of antioxidant genes and suppressing the expression of NADPH oxidant genes.
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