Novel Modulators of Human Sperm Motility
Male factor is the underlying cause in 50% cases of infertility, and is most commonly characterised by asthenozoospermia (reduced sperm motility). Incredibly, there is currently no known treatment for this condition, and the only option is Artificial Reproduction Technology (ART) which is expensive and invasive. The development of a novel treatment would fulfil a therapeutic niche that needs to be met. Using calcium as a surrogate for motility, a Flexstation high-throughput screening assay (HTS) of 3312 drug discovery ion channel compounds was performed. The screen identified 14 hit compounds that increase intracellular calcium in human spermatozoa. This project investigated these compounds, along with, 6 hit compounds previously identified from a HTS of a Chemogenomics library (246 compounds) for their potential to enhance sperm motility. One compound, Trequinsin hydrochloride (Chemogenomics library), produced statistically significant increases in progressive motility (P=0.02) instantaneously (t=0 min), an effect that was sustained for 3 hrs. Trequinsin hydrochloride, a potent class 3 phosphodiesterase inhibitor, along with B1, an ion channel compound, produced statistically significant increases in penetrating ability of spermatozoa through viscous medium. These compounds were both examined on sub-fertile patient samples, with positive results, providing preliminary data on their clinical relevance.
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