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  11. Ykl-40 Knockdown Decreases Oxidative Stress Damage In Ovarian Granulosa Cells

YKL-40 Knockdown Decreases Oxidative Stress Damage in Ovarian Granulosa Cells

Tingting Tang1, Jinyu Gao1, Xiangyang Pan1

  • 1Reproductive Medicine Center, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China.

Genetic Testing and Molecular Biomarkers
|April 18, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Elevated YKL-40 in polycystic ovarian syndrome (PCOS) follicular fluid and ovaries suggests a role in oxidative stress. Reducing YKL-40 in ovarian granulosa cells mitigates oxidative damage and inflammation.

Area of Science:

  • Reproductive Endocrinology
  • Molecular Biology
  • Biochemistry

Background:

  • Oxidative stress is a key factor in polycystic ovarian syndrome (PCOS) pathogenesis.
  • YKL-40, a chitinase-like protein, is elevated in PCOS but its specific role in ovarian oxidative stress is unclear.
  • Understanding YKL-40's function is crucial for developing novel antioxidant therapies for PCOS.

Purpose of the Study:

  • To investigate the role of YKL-40 in oxidative stress within the context of PCOS.
  • To determine the effect of YKL-40 knockdown on ovarian granulosa cells (OGCs) under oxidative stress.
  • To explore the impact of YKL-40 on cellular functions and signaling pathways involved in PCOS pathophysiology.

Main Methods:

  • Measured YKL-40 levels in follicular fluid from women with PCOS and controls using ELISA.
Keywords:
H2O2PI3K/AKT/NF-κBYKL-40follicular fluid

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  • Assessed ovarian YKL-40 expression in a letrozole-induced PCOS rat model via immunohistochemistry.
  • Utilized hydrogen peroxide (H₂O₂) to induce oxidative stress in KGN cells (OGCs) and employed siRNA for YKL-40 knockdown, followed by various assays to evaluate cellular responses and signaling pathways (PI3K/AKT/NF-κB).

    • Main Results:

    • YKL-40 levels were significantly higher in follicular fluid of PCOS patients and ovarian tissue of PCOS rats compared to controls.
    • H₂O₂ treatment increased YKL-40 expression in OGCs.
    • YKL-40 knockdown in H₂O₂-treated OGCs improved cell proliferation, enhanced antioxidant enzyme activity (T-SOD, GSH-Px, CAT), reduced MDA and inflammatory markers (IL-1β, IL-6, IL-8, TNF-α), decreased apoptosis, and activated the PI3K/AKT pathway while inhibiting NF-κB activation.

    Conclusions:

    • YKL-40 is upregulated in PCOS and its expression is induced by oxidative stress.
    • Knockdown of YKL-40 protects ovarian granulosa cells against oxidative stress-induced damage.
    • YKL-40 plays a significant role in PCOS pathophysiology, potentially through modulation of the PI3K/AKT/NF-κB signaling pathway.
    ovarian granulosa cells
    oxidative stress