Assessing efficacy of ADCY10 inhibitors in cervical mucus

Male fertility depends on sperm motility, which enables sperm to traverse the female reproductive tract to the site of fertilization. Soluble adenylyl cyclase (sAC) is a key regulator of sperm motility, defining it as a promising non-hormonal contraceptive target for women and men. To evaluate the efficacy of sAC inhibitors under conditions mimicking the female reproductive tract, we employed a capillary assay using cervical mucus isolated from humans or cows as well as methylcellulose, a viscoelastic liquid that simulates cervical mucus. Addition of a sAC inhibitor, either directly to semen, modeling an on-demand male contraceptive, or to the cervical mucus, approximating a female contraceptive, effectively blocked sperm migration. These studies provide proof-of-concept for the efficacy of sAC inhibitors under physiologically relevant conditions.