Male contraceptive options and infertility treatments are limited, and almost all innovation has been limited to updates to medically assisted reproduction protocols and methods. To accelerate the development of drugs that can either improve or inhibit fertility, we established a small molecule library as a toolbox for assay development and screening campaigns using human spermatozoa. We have profiled all compounds in the Sperm Toolbox in several automated high-throughput assays that measure stimulation or inhibition of sperm motility or the acrosome reaction. We have assayed motility under non-capacitating and capacitating conditions to distinguish between pathways operating under these different physiological states. We also assayed cell viability to ensure any effects on sperm function are specific. A key advantage of our studies is that all compounds are assayed together in the same experimental conditions, which allows quantitative comparisons of their effects in complementary functional assays. We have combined the resulting datasets to generate fingerprints of the Sperm Toolbox compounds on sperm function. The data are included in an on-line R-based app for convenient querying.
PloS one. 2024 Feb 20*** epublish ***
Franz S Gruber, Anthony Richardson, Zoe C Johnston, Rachel Myles, Neil R Norcross, David P Day, Irene Georgiou, Laura Sesma-Sanz, Caroline Wilson, Kevin D Read, Sarah Martins da Silva, Christopher L R Barratt, Ian H Gilbert, Jason R Swedlow
Divisions of Computational Biology and Molecular, Cell and Developmental Biology, and National Phenotypic Screening Centre, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Division of Systems Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom.