A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activity
- University of Dundee, United Kingdom
Abstract
There is an urgent need to develop new methods for male contraception, however a major barrier to drug discovery has been the lack of validated targets and the absence of an effective high-throughput phenotypic screening system. To address this deficit, we developed a fully-automated robotic screening platform that provided quantitative evaluation of compound activity against two key attributes of human sperm function: motility and acrosome reaction. In order to accelerate contraceptive development, we screened the comprehensive collection of 12,000 molecules that make up the ReFRAME repurposing library, comprising nearly all the small molecules that have been approved or have undergone clinical development, or have significant preclinical profiling. We identified several compounds that potently inhibit motility representing either novel drug candidates or routes to target identification. This platform will now allow for major drug discovery programmes that address the critical gap in the contraceptive portfolio as well as uncover novel human sperm biology.
Data availability
Full data is available. Large files have been deposited :https://datadryad.org/stash/share/06d75FZ6GiPmme3HnKnkyTFbgKJ2mV0UVRaN-gVKoVE.
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Data from: A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activityDryad Digital Repository, doi:10.5061/dryad.jdfn2z36z.
Article and author information
Author details
Christopher LR Barratt
Funding
Bill and Melinda Gates Foundation (OPP1160989)
- Zoe C johnston
Bill and Melinda Gates Foundation (OPP1203050)
- Franz S Gruber
- Zoe C johnston
- Christopher LR Barratt
- Paul D Andrews
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The Funders did facilitate using the REFRAME library
Ethics
Human subjects: Written consent was obtained from each donor in accordance with the Human Fertilization and Embryology Authority (HFEA) Code of Practice (version 8) under local ethical approval (13/ES/0091) from the Tayside Committee of Medical Research Ethics B.
Copyright
© 2020, Gruber et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activity
eLife 9:e51739.
https://doi.org/10.7554/eLife.51739
