• PMID: 14976244
• Gene Name: ADCY1
• Condition: Associated with sperm motility defect, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility

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

Esposito G, Jaiswal BS, Xie F, Krajnc-Franken MA, Robben TJ, Strik AM, Kuil C, Philipsen RL, van Duin M, Conti M, Gossen JA.

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. FAU - Esposito, Gloria AU - Esposito G AD - Department of Pharmacology and Lead Discovery Unit, NV Organon, P.O. Box 20, 5340 BH, Oss, The Netherlands. FAU - Jaiswal, Bijay S AU - Jaiswal BS FAU - Xie, Fang AU - Xie F FAU - Krajnc-Franken, Magda A M AU - Krajnc-Franken MA FAU - Robben, Tamara J A A AU - Robben TJ FAU - Strik, Ankie M AU - Strik AM FAU - Kuil, Cor AU - Kuil C FAU - Philipsen, Ria L A AU - Philipsen RL FAU - van Duin, Marcel AU - van Duin M FAU - Conti, Marco AU - Conti M