A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activity

Abstract
Data availability
Article and author information
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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.

The following data sets were generated

(2019) Data from: A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activity
Dryad Digital Repository, doi:10.5061/dryad.jdfn2z36z.

http://dx.doi.org/10.5061/dryad.jdfn2z36z

Article and author information

Author details

Franz S Gruber

School of Life Sciences, University of Dundee, Dundee, United Kingdom

Competing interests
No competing interests declared.
Zoe C johnston

Division of Systems Medicine, University of Dundee, Dundee, United Kingdom

Competing interests
No competing interests declared.
Christopher LR Barratt

Division of Systems Medicine, University of Dundee, Dundee, United Kingdom

For correspondence
c.barratt@dundee.ac.uk

Competing interests
Christopher LR Barratt, Editor for RBMO, has received lecturing fees from Merck, Pharmasure and Ferring and was on the Scientific Advisory Panel for Ohana BioSciences.

"This ORCID iD identifies the author of this article:" 0000-0003-0062-9979
Paul D Andrews

School of Life Sciences, University of Dundee, Dundee, United Kingdom

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-7699-5604

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

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.