title: Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology.
abstract: Fertilization is well correlated with sperm concentration, rate of forward motility, and percentage of live, uncapacitated ejaculated spermatozoa, which is regulated in part by cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to their corresponding monophosphates, thereby counterbalancing the activities of cAMP and cGMP, and PDE11 is highly expressed in the testis, prostate, and developing spermatozoa. However, a physiological role of PDE11 is not known. We generated PDE11 knockout (PDE11-/-) mice to investigate the role of PDE11 in spermatozoa physiology. Ejaculated sperm from PDE11-/- mice displayed reduced sperm concentration, rate of forward progression, and percentage of live spermatozoa. Pre-ejaculated sperm from PDE11-/- mice displayed increased premature/spontaneous capacitance. These data are consistent with human data and suggest a role for PDE11 in spermatogenesis and fertilization potential. This is the first phenotype described for the PDE11-/- mouse and the first report of a physiological role for PDE11.
authors.affiliation: Discovery Biology, Pfizer Global Research and Development, Sandwich, Kent, UK. chris_wayman@sandwich.pfizer.com
authors.forename: C
authors.initials: C
authors.lastname: Wayman
authors.forename: S
authors.initials: S
authors.lastname: Phillips
authors.forename: C
authors.initials: C
authors.lastname: Lunny
authors.forename: T
authors.initials: T
authors.lastname: Webb
authors.forename: L
authors.initials: L
authors.lastname: Fawcett
authors.forename: R
authors.initials: R
authors.lastname: Baxendale
authors.forename: G
authors.initials: G
authors.lastname: Burgess
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010727:Phosphoric Diester Hydrolases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011467:Prostate / Q000201:enzymology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017385:Sequence Homology; D013075:Sperm Capacitation; D013076:Sperm Count; D013081:Sperm Motility; D013091:Spermatogenesis; D013094:Spermatozoa / Q000201:enzymology / Q000502:physiology*; D013737:Testis / Q000201:enzymology; D014162:Transfection
chemical_list: D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C406737:PDE11A protein, human; C520793:Pde11a protein, mouse; D006152:Cyclic GMP