Described in eLife, the robotic screening platform uses a fast microscope and image-processing tools that precisely track the very fast movement of human sperm, allowing the effects of drugs to be accurately measured. The system was used to rapidly test the efficacy of the ReFRAME collection, one of the world's largest collections of previously approved and clinically tested drugs. Around 13,000 drugs were tested to gauge their impact on both the motility (movement) and acrosome reaction (essential for fertilisation) of human sperm.
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"The conventional way to test drugs for contraceptive activity is prohibitively time-consuming,” said Dr Paul Andrews, who leads the National Phenotypic Screening Centre (NPSC) in Dundee. "This new system speeds up the process of drug hunting several thousand-fold. The automated system also uses a different method to examine the effects of drugs on a second critical aspect required for fertilisation, called the acrosome reaction. This dual platform now allows for major drug discovery programmes that address the critical gap in the contraceptive portfolio as well as uncover novel human sperm biology.
"By using live human sperm and examining their behaviour, or phenotype, in the presence of drugs and other chemicals, we hope to circumvent the need to second-guess which proteins are important for the cellular processes underlying sperm's fertilisation capacity."
Long considered a holy grail of medicine, a male contraceptive drug has proved stubbornly difficult to develop. According to the researchers, there are several reasons for this, including a relatively poor understanding of sperm biology, as well as the absence of a system to rapidly test the effects of drugs on sperm behaviour. The new automated platform provides a solution to the latter problem and could help redress the imbalance of contraceptive responsibility, which falls predominantly on women in the form of the contraceptive pill.
“This is a breakthrough in technology for the area,” said Chris Barratt, Professor of Reproductive Medicine at Dundee’s School of Medicine.
“It allows us for the first time to assess in large numbers how compounds can affect sperm function. Surprisingly there has been no effective, reversible and widely available form of contraception developed for the male since the condom and, as such, the burden falls largely to the female. Finding an effective male contraceptive would be a major step in addressing that inequality."
The research was funded by the Bill & Melinda Gates Foundation.
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