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First published online May 8, 2009
doi: 10.1242/10.1242/dev.035238

Development 136, 1869-1878 (2009)
Published by The Company of Biologists 2009
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Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte

Rachael P. Norris1, William J. Ratzan1, Marina Freudzon1, Lisa M. Mehlmann1, Judith Krall2, Matthew A. Movsesian2, Huanchen Wang3, Hengming Ke3, Viacheslav O. Nikolaev4,* and Laurinda A. Jaffe1,*

1 Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06032, USA.
2 Cardiology Section, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT 84148, and the Departments of Internal Medicine (Cardiology) and Pharmacology, University of Utah, Salt Lake City, UT 84132, USA.
3 Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
4 Institute of Pharmacology and Toxicology, University of Würzburg, D-97078 Würzburg, Germany.

* Authors for correspondence (e-mails: nikolaev{at}toxi.uni-wuerzburg.de; ljaffe{at}neuron.uchc.edu)

Accepted 1 April 2009

Mammalian oocytes are arrested in meiotic prophase by an inhibitory signal from the surrounding somatic cells in the ovarian follicle. In response to luteinizing hormone (LH), which binds to receptors on the somatic cells, the oocyte proceeds to second metaphase, where it can be fertilized. Here we investigate how the somatic cells regulate the prophase-to-metaphase transition in the oocyte, and show that the inhibitory signal from the somatic cells is cGMP. Using FRET-based cyclic nucleotide sensors in follicle-enclosed mouse oocytes, we find that cGMP passes through gap junctions into the oocyte, where it inhibits the hydrolysis of cAMP by the phosphodiesterase PDE3A. This inhibition maintains a high concentration of cAMP and thus blocks meiotic progression. LH reverses the inhibitory signal by lowering cGMP levels in the somatic cells (from ~2 µM to ~80 nM at 1 hour after LH stimulation) and by closing gap junctions between the somatic cells. The resulting decrease in oocyte cGMP (from ~1 µM to ~40 nM) relieves the inhibition of PDE3A, increasing its activity by ~5-fold. This causes a decrease in oocyte cAMP (from ~700 nM to ~140 nM), leading to the resumption of meiosis.

Key words: cAMP, cGMP, Gap junctions, Meiosis, Mouse ovarian follicle, Oocyte


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Development 2009 136: e1103. [Full Text]  





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