Improving male contraception by targeting the sperm enzymes responsible for fertilization

This project looks at a novel family of serine/threonine kinases known as testis-specific serine kinases (TSSKs). Our group predicts that TSSKs play an important role in sperm function. The fact that these kinases do not affect premature sperm make them exemplary candidates for roles in novel drug design regarding fertility.

We assessed the enzyme kinetics of TSSK1, specifically, by application of homogeneous assays and high-throughput screening. Through these methods, we tested for inhibitors that would block the activity of TSSK1. This allowed us to find a variety of inhibitors that sequestered its activity and made it possible to sort them based on sensitivity, specificity, and overall effectiveness. Two protein kinase inhibitors we have tested (H7 and H89) have been shown to sequester TSSK1 activity in experimental trials performed in-lab. The successful results observed during testing of inhibitors such as these allowed us to explore other inhibitors as potentially better candidates.

The anticipated outcome of this research is to ultimately develop reversible male contraceptives based off this inhibition of TSSK1. Our findings will set the basis for future studies involving human sperm function and will provide the scientific community with a better understanding of spermatogenesis. With this data we hope to help directly combat the societal issue of overpopulation by supplying the general public with alternative methods of safe contraception.