This blog series highlights pertinent publications that were featured in MCI's monthly newsletter editions in the first quarter of 2025. The purpose of this blog is to report interesting or relevant work from MCI Fellows, Grantees, staff members, and other community authors in the field of male contraception. This review, by several MCI grantees and luminaries in the field, summarizes the history and current status of YCT-529, an MCI-funded nonhormonal contraceptive currently in early clinical trials. Researchers have identified retinoic acid receptor alpha (RARα) as a promising target for non-hormonal male contraception. A new compound, YCT-529, selectively inhibits RARα and has shown strong results in mice—effectively inducing reversible infertility without affecting overall health. Now advancing through clinical development, YCT-529 could mark a major breakthrough in expanding male birth control options. Following the Dobbs ruling and the overturning of Roe v. Wade, reports have shown a rise in interest in permanent contraception methods, including vasectomy. This paper, with a lead author from MCI’s Youth Advisory Board, dives deeper, analyzing Google Trends and web traffic data that reveal a significant spike in public interest in novel male contraceptive options. Searches for "male birth control" more than doubled, and visits to male contraception websites surged, underscoring a growing demand for new methods in a shifting reproductive health landscape. This research, from the lab of MCI Grantee Jean-Ju Chung, has uncovered the critical role of the CatSperε subunit in the assembly and function of the sperm-specific CatSper calcium channel, essential for male fertility. The study shows that CatSperε’s extracellular domains are required for proper channel formation and activity during sperm capacitation. Male mice lacking this subunit are sterile, and attempts to restore function without the full protein failed. However, introducing a fragment of CatSperε during capacitation disrupted channel activity—offering a potential new target for non-hormonal male contraceptives. This publication outlines the preclinical development of ADAM, an injectable, two-component hydrogel designed for long-lasting and nonpermanent vas-occlusive contraception by MCI partner Contraline. Preclinical testing shows the gel is safe, durable, and selectively permeable—blocking sperm while allowing fluid flow. It forms quickly after injection, withstands normal pressures, and caused no significant adverse reactions in a 2-year canine study. ADAM offers hope for a long-lasting, reversible male contraceptive and is a strong candidate for future clinical trials. This review from the lab of MCI grantee and collaborator Dr. Gunda Georg highlights the promising potential of cyclin-dependent kinase 2 (CDK2) inhibitors as non-hormonal male contraceptives. Originally developed for cancer treatment, these compounds are now being explored for their ability to disrupt sperm development. The review covers the evolution of CDK2 inhibitors, current clinical trials, and innovative strategies like allosteric and covalent inhibitors, opening exciting possibilities for future male contraceptive options. This paper, from the lab of 2025 MCI Grantee Dr. Steven Tang, reveals how a naturally occurring antisperm antibody, OBF13, can block fertilization by binding to an allosteric site on murine sperm IZUMO1. This binding prevents a critical conformational change needed for IZUMO1 to interact with the egg receptor JUNO, disrupting sperm–egg adhesion and fusion. The study provides key structural insights into species-specific fertilization and highlights the potential of immunocontraceptives and immuno-infertility diagnostics. Are there any interesting publications about non-hormonal, reversible male contraception that you'd like to see featured? Please reach out to us and share your thoughts!
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