Preantral follicle growth is regulated by c-Jun-N-terminal kinase (JNK) pathway

Ozgur Oktem1, Erkan Buyuk, Kutluk Oktay

  • 1Laboratory of Fertility Preservation and Molecular Reproduction, Departments of Obstetrics & Gynecology, Cell Biology & Anatomy, and Medicine, New York Medical College, Valhalla, New York 10595, USA.

Insights

The c-Jun N-terminal kinase (JNK) pathway is crucial for preantral follicle growth and granulosa cell cycle control. Inhibiting JNK signaling halts follicle development and disrupts cell cycle progression at critical S and G2/M phases.

Area of Science:

  • Reproductive Biology
  • Cell Signaling
  • Molecular Endocrinology

Background:

  • The c-Jun N-terminal kinase (JNK) pathway is vital for cell cycle progression and mitosis.
  • Previous studies demonstrated JNK pathway activation in granulosa cells during follicular development.
  • This study investigates JNK's role in preantral follicle in-vitro growth and granulosa cell cycle regulation.

Purpose of the Study:

  • To determine the effect of JNK signaling inhibition on murine preantral follicle growth in vitro.
  • To analyze the impact of JNK inhibition on granulosa cell cycle progression.
  • To elucidate the specific cell cycle phases regulated by the JNK pathway in granulosa cells.

Main Methods:

  • Pharmacologic JNK inhibitors (SP600125, AS601245) were used to assess their effects.
  • Inhibitory concentrations were determined in granulosa cells via Western blot.
  • Murine preantral follicles and synchronized granulosa cells were cultured and treated with JNK inhibitors.
  • Cell cycle progression was analyzed using Bromodeoxyuridine (BrdU) assay and flow cytometry.

Main Results:

  • Both JNK inhibitors significantly reduced c-Jun phosphorylation in granulosa cells.
  • In-vitro culture of preantral follicles with JNK inhibitors resulted in dose-dependent growth arrest.
  • JNK inhibition impaired granulosa cell cycle progression at the S phase and G2/M transition.

Conclusions:

  • The JNK pathway is essential for the in-vitro growth of murine preantral follicles.
  • JNK signaling regulates granulosa cell cycle progression at both S phase and G2/M transition.
  • Targeting the JNK pathway offers a potential strategy for controlling follicular development.

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