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Characterization of the effects of metformin on porcine oocyte meiosis and on AMP-activated protein kinase activation in oocytes and cumulus cells

Published online by Cambridge University Press:  12 April 2013

Sylvie Bilodeau-Goeseels ,
Nora Magyara  and
Coralie Collignon
Sylvie Bilodeau-Goeseels*
Affiliation:
Agriculture and Agri-Food Canada, Lethbridge Research Centre 5403 1st Avenue South, Lethbridge, Alberta T1J 4B1, Canada.
Nora Magyara
Affiliation:
Agriculture and Agri-Food Canada, Lethbridge Research Centre, 5403 1st Avenue South, Lethbridge, Alberta T1J 4B1, Canada.
Coralie Collignon
Affiliation:
VetAgro Sup Campus Agronomique de Clermont-Ferrand, 89 Avenue de l'Europe, 63 370 Lempdes, France.
*
All correspondence to: Sylvie Bilodeau-Goeseels. Agriculture and Agri-Food Canada, Lethbridge Research Centre 5403 1st Avenue South, Lethbridge, Alberta T1J 4B1, Canada. Tel: +1 403 317–2290. Fax: +1 403 382–3156. e-mail: [email protected]
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Summary

The adenosine monophosphate-activated protein kinase (AMPK) activators 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR) and metformin (MET) inhibit resumption of meiosis in porcine cumulus-enclosed oocytes. The objective of this study was to characterize the inhibitory effect of MET on porcine oocyte meiosis by: (1) determining the effects of an AMPK inhibitor and of inhibitors of signalling pathways involved in MET-induced AMPK activation in other cell types on MET-mediated meiotic arrest in porcine cumulus-enclosed oocytes; (2) determining whether MET and AICAR treatments lead to increased activation of porcine oocyte and/or cumulus cell AMPK as measured by phosphorylation of its substrate acetyl-CoA carboxylase; and (3) determining the effects of inhibition of the AMPK kinase, Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), and Ca2+ chelation on oocyte meiotic maturation and AMPK activation in porcine oocytes and cumulus cells. The AMPK inhibitor compound C (CC; 1 μM) did not reverse the inhibitory effect of AICAR (1 mM) and MET (2 mM) on porcine oocyte meiosis. Additionally, CC had a significant inhibitory effect on its own. eNOS, c-Src and PI-3 kinase pathway inhibitors did not reverse the effect of metformin on porcine oocyte meiosis. The level of acetyl-CoA carboxylase (ACC) phosphorylation in oocytes and cumulus cells did not change in response to culture in the presence of MET, AICAR, CC, the CaMKK inhibitor STO-609 or the Ca2+ chelator BAPTA-AM for 3 h, but STO-609 increased the percentage of porcine cumulus-enclosed oocytes (CEO) that remained at the germinal vesicle (GV) stage after 24 h of culture. These results indicate that the inhibitory effect of MET and AICAR on porcine oocyte meiosis was probably not mediated through activation of AMPK.

Keywords

Acetyl-CoA carboxylaseAMP-activated Protein kinaseMeiosisMetforminOocyte
Type
Research Article
Information
Zygote , Volume 22 , Issue 2 , May 2014 , pp. 275 - 285
Copyright
Copyright © Her Majesty the Queen in Right of Canada, as represented by the Minister of Agriculture and Agri-Food Canada 2013 

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