Quercetin supports bovine preimplantation embryo development under oxidative stress condition via activation of the Nrf2 signalling pathway

Khadrawy, Omar; Gebremedhn, Samuel; Salilew‐Wondim, Dessie; Rings, F.; Neuhoff, Christiane; Hoelker, M.; Schellander, K.; Tesfaye, Dawit

doi:10.1111/rda.13688

Cited by 14 publications

(8 citation statements)

References 65 publications

(110 reference statements)

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“…In the present study, blastocyst rates and total cell number were barely affected by the modulation of metabolites. Similar outcomes were already reported in different studies, in which modulators of metabolism, such as antioxidants and growth factors, altered the physiological response without affecting morphological parameters and blastocyst rates [29][30][31][32][33]. These results reinforce the importance of pursuing the improvement of IVP systems beyond the morphological aspect (those mostly used for the assessment of IVP success or embryo viability).…”

Section: Discussionsupporting

confidence: 87%

Tricarboxylic Acid Cycle Metabolites as Mediators of DNA Methylation Reprogramming in Bovine Preimplantation Embryos

Ispada

Junior

Lima

et al. 2020

IJMS

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In many cell types, epigenetic changes are partially regulated by the availability of metabolites involved in the activity of chromatin-modifying enzymes. Even so, the association between metabolism and the typical epigenetic reprogramming that occurs during preimplantation embryo development remains poorly understood. In this work, we explore the link between energy metabolism, more specifically the tricarboxylic acid cycle (TCA), and epigenetic regulation in bovine preimplantation embryos. Using a morphokinetics model of embryonic development (fast- and slow-developing embryos), we show that DNA methylation (5mC) and hydroxymethylation (5hmC) are dynamically regulated and altered by the speed of the first cleavages. More specifically, slow-developing embryos fail to perform the typical reprogramming that is necessary to ensure the generation of blastocysts with higher ability to establish specific cell lineages. Transcriptome analysis revealed that such differences were mainly associated with enzymes involved in the TCA cycle rather than specific writers/erasers of DNA methylation marks. This relationship was later confirmed by disturbing the embryonic metabolism through changes in α-ketoglutarate or succinate availability in culture media. This was sufficient to interfere with the DNA methylation dynamics despite the fact that blastocyst rates and total cell number were not quite affected. These results provide the first evidence of a relationship between epigenetic reprogramming and energy metabolism in bovine embryos. Likewise, levels of metabolites in culture media may be crucial for precise epigenetic reprogramming, with possible further consequences in the molecular control and differentiation of cells.

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Section: Discussionsupporting

confidence: 87%

Tricarboxylic Acid Cycle Metabolites as Mediators of DNA Methylation Reprogramming in Bovine Preimplantation Embryos

Ispada

Junior

Lima

et al. 2020

IJMS

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“…While we found this association to be irrespective of the steroidogenesis performance of heat-treated GCs, at 40.5 • C, the active steroid synthesis from GCs might accelerate the generation of reactive oxygen species (ROS) [14], in turn causing a clear increase in NFE2L2 and SOD2 gene expression. These increases in stress resistance transcripts as shown in the current study might be considered as a defense mechanism against high levels of superoxide radical-associated metabolic activity in response to active steroid secretion [28][29][30][31]. Thus excessive ROS production was counteracted by activating scavenging machinery through the (NFE2L2) NRF2-mediated oxidative stress response mechanism and its downstream antioxidant genes in bovine GCs [32] and preimplantation embryos [29].…”

Section: Discussionsupporting

confidence: 56%

“…These increases in stress resistance transcripts as shown in the current study might be considered as a defense mechanism against high levels of superoxide radical-associated metabolic activity in response to active steroid secretion [28][29][30][31]. Thus excessive ROS production was counteracted by activating scavenging machinery through the (NFE2L2) NRF2-mediated oxidative stress response mechanism and its downstream antioxidant genes in bovine GCs [32] and preimplantation embryos [29]. However, bovine GCs were unable to exhibit sufficient cellular protection at a prolonged exposure to 40 • C despite the rise in heat shock response protein as a defense mechanism [14].…”

Section: Discussionmentioning

confidence: 59%

Adaptive and Biological Responses of Buffalo Granulosa Cells Exposed to Heat Stress under In Vitro Condition

Faheem

Ghanem

Gad

et al. 2021

Animals

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The steroidogenesis capacity and adaptive response of follicular granulosa cells (GCs) to heat stress were assessed together with the underlying regulating molecular mechanisms in Egyptian buffalo. In vitro cultured GCs were exposed to heat stress treatments at 39.5, 40.5, or 41.5 °C for the final 24 h of the culture period (7 days), while the control group was kept under normal conditions (37 °C). Comparable viability was observed between the control and heat-treated GCs at 39.5 and 40.5 °C. A higher release of E2, P4 and IGF-1 was observed in the 40.5 °C group compared with the 39.5 or 41.5 °C groups. The total antioxidant capacity was higher in response to heat stress at 39.5 °C. At 40.5 °C, a significant upregulation pattern was found in the expression of the stress resistance transcripts (SOD2 and NFE2L2) and of CPT2. The relative abundance of ATP5F1A was significantly downregulated for all heat-treated groups compared to the control, while TNFα was downregulated in GCs at 39.5 °C. Expression analyses of stress-related miRNAs (miR-1246, miR-181a and miR-27b) exhibited a significant downregulation in the 40.5 °C group compared to the control, whereas miR-708 was upregulated in the 39.5 and 40.5 °C groups. In conclusion, buffalo GCs exhibited different adaptive responses, to the different heat stress conditions. The integration mechanism between the molecular and secretory actions of the GCs cultured at 40.5 °C might provide possible insights into the biological mechanism through which buffalo GCs react to heat stress.

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“…The bitter flavor of quercetin makes it a popular component in nutritional supplements, drinks, and meals. 103 Quercetin attenuates oxidative DNA damage 104 and inflammatory responses in BV-2 microglial cells 105 and supports bovine preimplantation embryo development under OS condition 106 through the down-regulation of the pro-inflammatory pathway involving NF-κB and up-regulation of the antioxidative pathway involving Nrf2. Proteostasis: Hsp90/Hsf1 Pathway.…”

Section: Discussion: Redox Regulation and Therapeutic Perspectives Of...mentioning

confidence: 95%

Redox Activity of Flavonoids: Impact on Human Health, Therapeutics, and Chemical Safety

Sarkar

Chaudhary

Jamaddar

et al. 2022

Chem. Res. Toxicol.

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The cost-effectiveness of presently used therapies is a problem in overall redox-based management, which is posing a significant financial burden on communities across the world. As a result, sophisticated treatment models that provide notions of predictive diagnoses followed by targeted preventive therapies adapted to individual patient profiles are gaining global acclaim as being beneficial to patients, the healthcare sector, and society as a whole. In this context, natural flavonoids were considered due to their multifaceted antioxidant, anti-inflammatory, and anticancer effects as well as their low toxicity and ease of availability. The aim of this review is to focus on the capacity of flavonoids to modulate the responsiveness of various diseases and ailments associated with redox toxicity. The review will also focus on the flavonoids' pathway-based redox activity and the advancement of redox-based therapies as well as flavonoids' antioxidant characteristics and their influence on human health, therapeutics, and chemical safety. Research findings indicated that flavonoids significantly exhibit various redox-based therapeutic responses against several diseases such as inflammatory, neurodegenerative, cardiovascular, and hepatic diseases and various types of cancer by activating the Nrf2/Keap1 transcription system, suppressing the nuclear factor κB (NF-κB)/IκB kinase inflammatory pathway, abrogating the function of the Hsp90/Hsf1 complex, inhibiting the PTEN/PI3K/Akt pathway, and preventing mitochondrial dysfunction. Some flavonoids, especially genistein, apigenin, amentoflavone, baicalein, quercetin, licochalcone A, and biochanin A, play a potential role in redox regulation. Conclusions of this review on the antioxidant aspects of flavonoids highlight the medicinal and folk values of these compounds against oxidative stress and various diseases and ailments. In short, treatment with flavonoids could be a novel therapeutic invention in clinical trials, as we hope.

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Quercetin supports bovine preimplantation embryo development under oxidative stress condition via activation of the Nrf2 signalling pathway

Cited by 14 publications

References 65 publications

Tricarboxylic Acid Cycle Metabolites as Mediators of DNA Methylation Reprogramming in Bovine Preimplantation Embryos

Tricarboxylic Acid Cycle Metabolites as Mediators of DNA Methylation Reprogramming in Bovine Preimplantation Embryos

Adaptive and Biological Responses of Buffalo Granulosa Cells Exposed to Heat Stress under In Vitro Condition

Redox Activity of Flavonoids: Impact on Human Health, Therapeutics, and Chemical Safety

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