There were several attempts to uncover tiny compounds that modulate sperm activity, but none have used high-throughput technologies. Semen samples from healthy donors were used, and samples were pooled (3–5 donors per pool). The primary screening was done once, and the dose-response screening was done twice (using independent donor pools). Spermatozoa from healthy volunteers were produced using density gradient centrifugation and then treated in 384-well plates with chemicals (6.25 μM) to find those that improved motility. A total of 17,000 compounds were screened from the libraries ReFRAME, Prestwick, Tocris, LOPAC, CLOUD, and MMV Pathogen Box. Dose-response studies of screening hits were conducted to establish the boosting effect on sperm motility. Experiments were carried out at a university. Compared with dimethylsulphoxide-treated wells, 105 substances elicited an increasing impact on sperm motility in our primary single concentration screening. The annotated targets/target classes were used to the group confirmed boosting imports. Phosphodiesterase inhibitors, particularly PDE10A inhibitors, and several chemicals not previously recognized to improve human sperm motility, such as those related to GABA signaling, were discovered as a prominent target class. Many drugs that improved sperm motility were found using this phenotypic screening assay. Researchers highlighted prospective molecules as a promising start-point for a medicinal chemistry program for the potential enhancement of male fertility and enhancing the understanding of human sperm function, such as uncovering new paths for discovery. Furthermore, they provided a valuable resource for future research in the sector by disclosing the screening results.
Source:academic.oup.com/humrep/article/37/3/466/6511992
