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Published on: October 13, 2018
Impaired growth and fertility of cAMP-specific phosphodiesterase PDE4D-deficient mice
S L Jin1, F J Richard, W P Kuo
1Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.
Abstract:
In eukaryotic cells, the inactivation of the cyclic nucleotide signal depends on a complex array of cyclic nucleotide phosphodiesterases (PDEs). Although it has been established that multiple PDE isoenzymes with distinct catalytic properties and regulations coexist in the same cell, the physiological significance of this remarkable complexity is poorly understood. To examine the role of a PDE in cAMP signaling in vivo, we have inactivated the type 4 cAMP-specific PDE (PDE4D) gene, a mammalian homologue of the Drosophila dunce. This isoenzyme is involved in feedback regulation of cAMP levels. Mice deficient in PDE4D exhibit delayed growth as well as reduced viability and female fertility. The decrease in fertility of the null female is caused by impaired ovulation and diminished sensitivity of the granulosa cells to gonadotropins. These pleiotropic phenotypes demonstrate that PDE4D plays a critical role in cAMP signaling and that the activity of this isoenzyme is required for the regulation of growth and fertility.
Insights
Inactivating the PDE4D gene impairs female fertility and growth in mice by disrupting cyclic adenosine monophosphate (cAMP) signaling pathways. This highlights PDE4D
Area of Science:
- Molecular Biology
- Cellular Signaling
- Genetics
Background:
- Eukaryotic cells utilize cyclic nucleotide phosphodiesterases (PDEs) to regulate cyclic nucleotide signaling.
- The physiological roles of multiple coexisting PDE isoenzymes remain poorly understood.
- PDE4D is a cAMP-specific isoenzyme involved in the feedback regulation of cAMP levels.
Purpose of the Study:
- To investigate the in vivo role of the PDE4D gene in cyclic adenosine monophosphate (cAMP) signaling.
- To elucidate the physiological significance of PDE4D in regulating growth and fertility.
Main Methods:
- Gene inactivation of the type 4 cAMP-specific phosphodiesterase (PDE4D) in mice.
- Phenotypic analysis of PDE4D-deficient mice, including growth, viability, and reproductive parameters.
- Assessment of ovulation and granulosa cell sensitivity to gonadotropins in null females.
Main Results:
- PDE4D-deficient mice exhibited delayed growth, reduced viability, and impaired female fertility.
- Female infertility was linked to defective ovulation and decreased granulosa cell responsiveness to gonadotropins.
- These findings indicate pleiotropic effects of PDE4D deficiency on physiological processes.
Conclusions:
- PDE4D plays a critical role in regulating cAMP signaling in vivo.
- The activity of PDE4D is essential for the proper regulation of mammalian growth and female reproductive functions.
- Understanding PDE4D function is crucial for comprehending complex cellular signaling networks.
