Female infertility cAMP

In mammals, the development of the egg in the ovary is halted until just before ovulation, at which point the final cellular division to form the egg, called meiosis, is completed. Researchers have shown that this final step in egg maturation can be blocked by a chemical called cyclic AMP (cAMP) in a test tube, but it remained uncertain whether the same molecular mechanism occurred in the animal.

To investigate this process, Vincent Manganiello and colleagues, from the National Institutes of Health, created a mouse that is missing a gene for a protein whose function is to breakdown cAMP in the developing egg. This gene is called cyclic nucleotide phosphodiesterase 3A or Pde3a. Male mice that are missing their Pde3a gene are healthy and completely fertile. Female mice without the Pde3a gene are likewise healthy and can carry out ovulation, but they are completely infertile.

The researchers showed that in the developing eggsin the absence of any PDE breakdown of cAMP, that cAMP levels were substantially higher and that the developing eggs were frozen at a stage just prior to the completion of meiosis. The researchers then showed that by blocking the activity of another protein in the cAMP molecular signaling pathway, egg maturation could be completed. The reversible nature of the infertility block caused by loss of the Pde3a gene suggests that PDE3A may be a potential target for developing new contraceptives.

The Pde3a knockout mouse will be an excellent model of female infertility for exploring this further.

Author contact:
Vincent Manganiello
NIH
9000 Rockville Pike
Bethesda, Maryland 20892
USA
ManganiV@nhlbi.nih.gov
Tel: 301-496-1770
Fax: 301-402-1610

View the PDF of this article at: http://www.jci.org/cgi/content/full/114/2/196

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