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Cilostamide and rolipram prevent spontaneous meiotic resumption from diplotene arrest in rat oocytes cultured in

Anumegha Gupta1, Shail K Chaube1

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

European Journal of Pharmacology
|April 18, 2020
PubMed

Insights

Cilostamide and rolipram inhibit spontaneous meiotic resumption in rat oocytes by affecting phosphodiesterases (PDEs) and cAMP levels. Cilostamide is more potent, suggesting its potential as a female contraceptive drug.

Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Cellular Signaling

Background:

  • Spontaneous meiotic resumption in oocytes is regulated by cyclic adenosine monophosphate (cAMP) and phosphodiesterases (PDEs).
  • The specific roles of PDE 3A and PDE 4D in oocyte meiotic resumption are not fully understood.
  • Understanding these pathways is crucial for developing novel contraceptive strategies.

Purpose of the Study:

  • To investigate the effects of PDE 3A inhibitor cilostamide and PDE 4D inhibitor rolipram on spontaneous meiotic resumption in rat oocytes.
  • To elucidate the involvement of the PDE 3A/PDE 4D-cAMP pathway in regulating oocyte meiotic arrest.

Main Methods:

  • Rat oocytes (cumulus oocyte complexes and denuded oocytes) arrested at the diplotene stage were cultured in vitro.
  • Oocytes were treated with varying concentrations and durations of cilostamide and rolipram.
  • PDE expression, cAMP levels, and meiotic resumption were assessed.

Main Results:

  • Cilostamide significantly inhibited spontaneous meiotic resumption in a dose- and time-dependent manner.
  • Rolipram showed partial inhibition, but cilostamide was more potent in preventing meiotic resumption.
  • Cilostamide reduced PDE 3A expression and increased cAMP levels, effectively preventing meiotic resumption.

Conclusions:

  • Both cilostamide and rolipram prevent spontaneous meiotic resumption via the PDE 3A/PDE 4D-cAMP pathway.
  • Cilostamide demonstrates superior potency compared to rolipram in inhibiting meiotic resumption.
  • Cilostamide shows promise as a potential candidate for future female contraceptive development.
Keywords:
CilostamideDiplotene arrestPhosphodiesterasesRat oocytesRolipramcAMP

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