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The future of male infertility treatment

Published: 05 Nov 2019
Category: Young pharmacologists
By Rachel McBrinn

Despite living in a generation that is more expressive and open to change, male infertility is still quite a taboo subject, making it an under-acknowledged problem. Approximately 1 in 20 men have a fertility issue, with asthenozoospermia (poor sperm swimming) being the most common problem. However, there is currently no treatment or cure. Intracytoplasmic sperm injection (ICSI) is the most likely treatment option, but this is invasive, removes all-natural selection steps and places the burden of treatment on the woman. The lack of male treatment options is ultimately comes down to our limited understanding of normal sperm function. Sperm cells are incredibly unique and highly specialised cells. Our ultimate goal is to develop a drug that can improve how a man’s sperm swim, or to be used in vitro to improve fertilisation success.

My team received funding from the Scottish Government’s Chief Scientist Office and the Medical Research Council to progress our understanding of normal and dysfunctional sperm and facilitate our drug-discovery goal. Here in the heart of Dundee, our team at Ninewells Hospital, in collaboration with the University of Dundee’s Drug Discovery Unit and Abertay University, identified trequinsin hydrochloride from a panel of small-molecule compounds. It improved sperm motility in both healthy-donor and patient populations. Importantly, we used an effective screening strategy to narrow down how the compound achieved this. Using advanced techniques such as high-performance liquid chromatography, patch-clamp electrophysiology, and intracellular calcium measurement, we demonstrated how this compound boosts motility and sperm cell penetration:
 
  • via sperm-specific calcium and potassium channels
  • via cyclic nucleotide (cyclic guanosine monophosphate) signalling.
Our research group has published several studies on sperm drug discovery. This is an exciting time for research into the causes and treatments of male fertility as we push the theoretical and technical boundaries. Using advanced screening strategies, we can identify compounds like trequinsin hydrochloride that increase the functionality of sperm and aid successful fertilisation. As I near the end of my PhD, I hope that the research I have contributed to helps establish a much-needed drug for male infertility.
 

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About the author

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Rachel McBrinn is a PhD student at Abertay University, where she specialises in the use of high-performance liquid chromatography to measure cyclic nucleotide activity in human sperm. Collaborating with the Reproductive Medicine Group at Ninewells Hospital in Dundee, Rachel’s biggest achievement is identifying the mechanistic actions of trequinsin hydrochloride to improve sperm movement. Her life’s ambition to see a readily available male fertility drug.