A complex phenotypic assay of mammalian oocyte maturation identifies compounds that block meiotic progression for non-hormonal contraceptive discovery

Despite the prevalent use and efficacy of hormonal contraception, it remains unsuitable for many due to the prevalence of perceived and actual side effects. Thus, there is a need for novel contraceptives for women worldwide, especially non-hormonal options. During ovulation, oocytes undergo a maturation process by which they progress through meiosis, a specialized cell division needed to reduce chromosome content. Given that meiotic progression is essential for generating a fertilizable egg but does not affect hormone production, it represents a promising biological mechanism to target for female non-hormonal contraception. In this study, we developed a phenotypic screening platform modeled after biopharmaceutical industry practices using mouse oocytes to screen for compounds that block meiotic progression. Oocytes were matured in vitro in the presence of selected compounds from a bioactive compound library, and confirmed hits were identified as those that potently and reproducibly blocked meiotic progression. In addition, we showed that the inhibitory effect of these compounds was persistent and reversible. Thus, our oocyte drug screening pipeline provides a powerful system to identify novel drug discovery candidates for further follow up for non-hormonal contraception development.