Khadrawy, Omar Zainelabdeen Shehata: Modulation of Nrf2-mediated oxidative stress response in bovine granulosa cells and preimplantation embryos. - Bonn, 2019. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
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author = {{Omar Zainelabdeen Shehata Khadrawy}},
title = {Modulation of Nrf2-mediated oxidative stress response in bovine granulosa cells and preimplantation embryos},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2019,
month = nov,

volume = 189,
note = {Nrf2 is a redox sensitive transcription factor involved in regulation of antioxidants defense mechanism against various stressors. Maintaining reactive oxygen species (ROS) within cellular homeostatic levels is crucial for the female reproductive performance and ovarian ability to develop a competent oocyte capable to be fertilized and developed to competent embryo. However, Nrf2 is found to be regulated at transcriptional and posttranscriptional levels and various epigenetic mechanisms including DNA methylation, histone modifications and miRNAs. Therefore, this dissertation aims to assess the potential role of noncoding miRNAs as endogenous and quercetin as exogenous regulators of Nrf2 pathway in bovine granulosa cells and preimplantation embryos. For this, two main experiments were conducted; where bovine granulosa cells were used for modulation of miRNAs (miR-28, 153 and miR-708) targeting the bovine Nrf2 and supplementation of quercentin to investigate the regulatory mechanisms of the Nrf2 antioxidant system. In addition, cultured cells exposed to oxidative stress conditions induced by hydrogen peroxide (H2O2) in those cells. Cells of all experimental groups were subjected to ROS level, mitochondrial activity and cell proliferation assays as well as mRNA and protein expression analyses. In the second experiment, bovine embryos were cultured in media supplemented with quercetin under high oxygen tension (20 %). Blastocysts were subjected to ROS level, mitochondrial activity, mRNA expression and protein analysis. Overexpression of miR-153, miR-28 and miR-708 reduced the expression pattern of Nrf2 at transcriptional and translational levels under physiological and oxidative stress conditions. Moreover, overexpression of miR-153 and miR-28\708 showed higher ROS accumulation, lower mitochondrial activity and cellular proliferation. Furthermore, quercetin supplementation in culture media showed a protective role on bovine granulosa cells and preimplantation embryos against oxidative stress induced by H2O2 and high oxygen level, respectively through activation of Nrf2 machinery leading to reduce ROS accumulation, increased mitochondrial activity and cellular proliferation and embryonic total cell number. These findings highlighted the regulatory mechanisms of Nrf2 mediated oxidative stress response pathway in bovine granulosa cells, preimplantation embryos and indicate the potential application of those regulatory mechanisms in future fertility treatment strategies to enhance ovarian functionality and embryo quality under suboptimal conditions.},
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