Document Detail

Characterization of novel phosphodiesterases in the bovine ovarian follicle.
MedLine Citation:
PMID:  19357367     Owner:  NLM     Status:  MEDLINE    
The phosphodiesterase (PDE) family is a group of enzymes that catalyzes the transformation of cyclic nucleotides into 5' nucleotides. Based on rodents, the current mammalian model of PDE distribution in the ovarian follicle predicts Pde3a in the oocyte and Pde4d in the somatic cells. Using bovine as an experimental model, the present results showed that PDE3 was the predominant PDE activity in oocytes. However, cumulus cell cAMP-PDE activity was predominantly resistant to inhibition by 3-isobutyl-methylxantine, indicating PDE8 activity (60% of total PDE activity) and a minor role for PDE4 (<5%). A total of 20% of total oocyte PDE activity was also attributed to PDE8. The PDE activity measurements in mural granulosa cells from 2 to 6 mm in diameter suggest the presence of PDE4 and PDE8. In granulosa cells from follicles >10 mm, total PDE and PDE8 activities along with PDE8A protein level were increased compared with smaller follicles. The RT-PCR experiments showed that cumulus cells expressed PDE8A, PDE8B, and PDE10A. Western blot experiments showed PDE8A, PDE8B, and PDE4D proteins in mural granulosa cells and cumulus-oocyte complexes. PDE8 inhibition using dipyridamole in a dose-dependent manner increased cAMP levels in the cumulus-oocyte complexes and delayed oocyte nuclear maturation. These results are the first to demonstrate the functional presence of PDE8 in the mammalian ovarian follicle. This challenges the recently described cell-specific expression of cAMP-PDEs in the ovarian follicle and the notion that PDE4 is the predominant granulosa/cumulus cell PDE. These findings have implications for our understanding of hormonal regulation of folliculogenesis and the potential application of PDE inhibitors as novel contraceptives.
Maxime Sasseville; Firas K Albuz; Nancy Côté; Christine Guillemette; Robert B Gilchrist; François J Richard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-08
Journal Detail:
Title:  Biology of reproduction     Volume:  81     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-22     Completed Date:  2009-11-30     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  415-25     Citation Subset:  IM    
Département des Sciences Animales, Centre de Recherche en Biologie de la Reproduction, Université Laval, Sainte-Foy, Québec, Canada.
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MeSH Terms
Adenylate Cyclase / metabolism
Analysis of Variance
Cell Nucleus / physiology
Contraceptive Agents, Female
Cyclic AMP / metabolism
Embryo Culture Techniques
Fertilization in Vitro
Granulosa Cells / drug effects,  enzymology*
Isoenzymes / genetics,  metabolism
Oocytes / drug effects,  enzymology*,  physiology
Oogenesis / drug effects*
Ovarian Follicle / enzymology*
Phosphodiesterase Inhibitors / pharmacology*
Phosphoric Diester Hydrolases / genetics,  metabolism*
Protein Transport
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/Contraceptive Agents, Female; 0/Isoenzymes; 0/Phosphodiesterase Inhibitors; 60-92-4/Cyclic AMP; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC Cyclase

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