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Downregulation of PI3K/AKT/mTOR Pathway in Juglone-Treated Bovine Oocytes

Marwa El-Sheikh1, Ayman Mesalam2, Atif Ali Khan Khalil3

  • 1Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre (NRC), Dokki, Cairo 12622, Egypt.

Antioxidants (Basel, Switzerland)
|January 21, 2023
PubMed

Insights

Juglone exposure during bovine oocyte maturation significantly impairs developmental competence by disrupting filamentous actin and downregulating key genes involved in meiosis, mitochondria, and survival pathways. This toxicity is linked to PI3K/AKT/mTOR signaling inhibition.

Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Toxicology

Background:

  • Juglone, a natural compound from Juglandaceae, exhibits diverse biological activities.
  • Previous studies indicated juglone reduces bovine oocyte developmental competence.
  • The precise mechanisms of juglone toxicity in oocytes remain unclear.

Purpose of the Study:

  • To investigate the toxicological mechanisms of juglone on bovine oocytes during in vitro maturation (IVM).
  • To explore the relationship between juglone toxicity and the PI3K/AKT/mTOR signaling pathway.

Main Methods:

  • Exposure of bovine oocytes to juglone during IVM.
  • Assessment of filamentous actin (F-actin) accumulation.
  • Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) for gene expression analysis.
  • Analysis of protein expression for PI3K/AKT/mTOR pathway components.
  • Evaluation of autophagy and DNA damage markers.

Main Results:

  • Juglone exposure decreased F-actin accumulation and downregulated genes related to meiosis (GSK-3A), oocyte development (BMP15), mitochondrial function (MFN1), oxidative stress (OGG1), and histone methylation (EZH1, EZH2, SUZ12, G9a, SUV39H2).
  • Expression of glycolysis (PFK1, GLUT1), ATP synthesis (ATPase8, ATP5F1B), oxidative phosphorylation (SDHA, SDHD), and survival regulators (SOD2, VEGF, MAPK1) were significantly reduced.
  • PI3K, AKT, and mTOR expression decreased at transcriptional and/or translational levels.
  • Autophagy markers (LC3B, beclin-1) and DNA damage marker (8-OxoG) were overexpressed.

Conclusions:

  • Juglone administration during IVM compromises bovine oocyte quality and developmental potential.
  • The toxicity mechanism involves the downregulation of the PI3K/AKT/mTOR pathway and its downstream signaling.
  • Juglone induces oxidative stress, impairs energy metabolism, and affects cytoskeletal organization in oocytes.
Keywords:
AKTPI3Khistone methylationjuglonemTORoocyte qualitysignaling

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