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Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect.


ABSTRACT: To acquire the ability to fertilize, spermatozoa undergo complex, but at present poorly understood, activation processes. The intracellular rise of cAMP produced by the bicarbonate-dependent soluble adenylyl cyclase (sAC) has been suggested to play a central role in initiating the cascade of the events that culminates in spermatozoa maturation. Here, we show that targeted disruption of the sAC gene does not affect spermatogenesis but dramatically impairs sperm motility, leading to male sterility. sAC mutant spermatozoa are characterized by a total loss of forward motility and are unable to fertilize oocytes in vitro. Interestingly, motility in sAC mutant spermatozoa can be restored on cAMP loading, indicating that the motility defect observed is not caused by a structural defect. We, therefore, conclude that sAC plays an essential and nonredundant role in the activation of the signaling cascade controlling motility and, therefore, in fertility. The crucial role of sAC in fertility and the absence of any other obvious pathological abnormalities in sAC-deficient mice may provide a rationale for developing inhibitors that can be applied as a human male contraceptive.

SUBMITTER: Esposito G 

PROVIDER: S-EPMC365733 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature

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Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect.

Esposito Gloria G   Jaiswal Bijay S BS   Xie Fang F   Krajnc-Franken Magda A M MA   Robben Tamara J A A TJ   Strik Ankie M AM   Kuil Cor C   Philipsen Ria L A RL   van Duin Marcel M   Conti Marco M   Gossen Jan A JA  

Proceedings of the National Academy of Sciences of the United States of America 20040219 9


To acquire the ability to fertilize, spermatozoa undergo complex, but at present poorly understood, activation processes. The intracellular rise of cAMP produced by the bicarbonate-dependent soluble adenylyl cyclase (sAC) has been suggested to play a central role in initiating the cascade of the events that culminates in spermatozoa maturation. Here, we show that targeted disruption of the sAC gene does not affect spermatogenesis but dramatically impairs sperm motility, leading to male sterility  ...[more]

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