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Mammalian sperm phosphodiesterases and their involvement in receptor-mediated cell signalling important for capacitation

Research output: Contribution to journalArticlepeer-review

R W Baxendale, L R Fraser

Original languageEnglish
Pages (from-to)495 - 508
Number of pages14
JournalMolecular Reproduction and Development
Volume71
Issue number4
DOIs
PublishedAug 2005

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  • King's College London

Abstract

This study investigated the presence and function of intracellular cyclic nucleotice phosphodiesterases (PDEs) in mature mouse spermatozoa. PCR analysis detected gene transcripts for most of the 11 known PDE families in whole testis, but mainly for PDEs 1, 3, 6, and 8 in spermatozoa. Using specific antibodies, the strongest evidence was obtained for PDE proteins 1, 4, 6, 8, 10, and 11 in both sperm lysates and intact cells. These showed a range of subcellular localizations, with PDE 1A being primarily in the flagellum but PDEs 4D and 10A being in both the acrosomal region and the flagellum, similar to specific G proteins and adenylyl cyclases implicated in cAMP regulation during capacitation. In live spermatozoa, inhibitors selective for PDE 1 (MMPX) and 4 (rolipram) significantly increased cAMP over control levels but only rolipram significantly stimulated capacitation and in-vitro fertilizing ability; this suggests that compartmentalization has functional implications since only PDE 4 was abundant in both head and flagellum. Treatment of spermatozoa with CGS 21680, a stimulatory adenosine receptor agonist, significantly reduced cAMP-PDE activity at the same time-point when it causes increased cAMP. Thus, certain receptor-regulated cAMP processes in spermatozoa may be controlled by changes in both PDE and cyclase activities. In addition to demonstrating for the first time that some of the more recently discovered PDE isoforms, including PDE 6 (usually associated with the retina), are present in mature spermatozoa, this study provides clear evidence that the intracellular location of specific PDEs has important functional significance during capacitation and fertilization

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