The world’s population has been steadily increasing, with projections showing that it will reach 9 billion by 2037, emphasizing the importance of family planning. However, there have been limited advancements in contraception in recent years, especially for men who do not have access to oral contraceptive pills. A new study published in the journal Science presents a novel non-hormonal approach to male contraception that offers a promising option for reversible birth control. Researchers at Baylor College of Medicine and collaborating institutions focused on targeting a protein called serine/threonine kinase 33 (STK33) that is essential for fertility in both men and mice.
Previous research has shown that STK33 is required for the formation of functional sperm in mice and humans. Knocking out the Stk33 gene in mice results in sterility due to abnormal sperm, and mutations in the STK33 gene in men lead to infertility with similar sperm defects. The researchers identified potent STK33 inhibitors using DNA-Encoded Chemistry Technology (DEC-Tec) and found that one compound, CDD-2807, was particularly effective. They tested this compound in mouse models and observed a significant reduction in sperm motility and numbers, ultimately leading to reversible male infertility. Importantly, the treatment did not have any toxic effects on the mice and did not accumulate in the brain.
In addition to testing the efficacy of CDD-2807 in animal models, the researchers also determined the crystal structure of STK33 and how the inhibitor interacts with the protein. This knowledge allowed them to optimize the compound for better drug-like properties. The study represents a significant step towards developing a male contraceptive pill that targets a specific protein involved in sperm production. The researchers plan to further evaluate the STK33 inhibitor and similar compounds in primates to determine their effectiveness as reversible male contraceptives.
The research team at Baylor College of Medicine, along with collaborators, demonstrated that targeting STK33 with a specific inhibitor could be a viable option for reversible male contraception. By focusing on a protein that is essential for sperm production but does not have other critical functions in the body, the researchers were able to develop a promising contraceptive strategy. The compound CDD-2807 effectively reduced sperm motility and numbers in mice without causing toxicity or altering testis size. The contraceptive effect was also reversible, allowing the mice to regain fertility after stopping treatment with CDD-2807.
The study highlights the potential for a non-hormonal, reversible male contraceptive option that specifically targets a protein involved in sperm production. The researchers used innovative techniques to identify and optimize a potent STK33 inhibitor, paving the way for further development and evaluation in primate models. This research represents a major step forward in the quest for male contraception options and provides hope for the development of a birth control pill for men in the future. Collaborations between institutions and interdisciplinary teams are crucial for advancing scientific discoveries and developing new contraceptive strategies to address the growing global population.