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Carbenoxolone reduces cyclic nucleotides level, destabilizes maturation promoting factor and induces meiotic exit

Meenakshi Tiwari1, Shail K Chaube1

  • 1Cell Physiology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi-221005, UP, India.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|August 2, 2017
PubMed
Abstract

Insights

Carbenoxolone (CBX) blocks gap junctions, reducing cyclic nucleotides and destabilizing maturation promoting factor (MPF) to induce meiotic exit from diplotene arrest (EDA) in rat oocytes. This finding suggests CBX could aid in assisted reproductive technology (ART) programs.

Area of Science:

  • Reproductive Biology
  • Cell Signaling
  • Developmental Biology

Background:

  • Meiotic exit from diplotene arrest (EDA) in mammals is linked to gap junction disruption and cyclic nucleotide transfer to the oocyte.
  • Gap junctions facilitate communication between cumulus cells and oocytes, influencing meiotic progression.

Purpose of the Study:

  • To investigate if carbenoxolone (CBX), a gap junction blocker, can induce EDA in rat oocytes.
  • To determine if CBX reduces cyclic nucleotide levels and destabilizes maturation promoting factor (MPF) in vitro.

Main Methods:

  • Rat oocytes at diplotene arrest were cultured with varying concentrations of CBX.
  • Analysis included morphological changes, meiotic status, nitric oxide synthase (iNOS), cyclic nucleotides (cAMP, cGMP), Cdc25B, and Cdk1/cyclin B1 phosphorylation status.

Main Results:

  • CBX induced EDA in a concentration-dependent manner.
  • CBX significantly decreased iNOS, nitric oxide, and cyclic nucleotide levels, leading to reduced Cdc25B expression.
  • CBX destabilized MPF by altering Cdk1 phosphorylation and reducing cyclin B1 levels, ultimately inducing EDA.

Conclusions:

  • CBX blocks gap junctions, interrupting cyclic nucleotide transfer and destabilizing MPF, thereby inducing EDA in vitro.
  • CBX shows potential for inducing meiotic maturation in oocytes for assisted reproductive technology (ART).
Keywords:
CBXDiplotene arrestMPFMeiotic exitRat oocytescAMP

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