Developing a Novel In Vitro Screening Model to Assess Male Contraceptives

Charles Easley of the University of Georgia Research Foundation in the U.S. is developing a complete human spermatogenesis model system for high-throughput drug screens to identify new compounds that reversibly block the maturation of sperm and could be used as male contraceptives. A simple oral male contraceptive would lessen the burden on women, particularly those who suffer from adverse side-effects of hormonal contraceptives. Their model involves inducing human pluripotent stem cells to differentiate into mature sperm cells, which occurs via intermediate cell types that can each be fluorescently labeled for high-throughput analyses. In Phase I, they demonstrated proof-of-concept by optimizing the culturing method for in vitro human spermatogenesis, and stably transducing several human pluripotent stem cell lines with individual fluorescent reporter constructs. These cell lines were then induced to differentiate, and the reporters were confirmed to be functional. In Phase II, they will use this platform to conduct screens of candidate contraceptive compounds. Hit compounds will be subjected to metabolomics and bioinformatics approaches to identify their mechanisms of action, and their reversibility and specificity. Finally, they will develop a three-dimensional model of human spermatogenesis using testis tissue from and use it to retest their hit compounds and evaluate them for any potential adverse side-effects.