Divisions of Computational Biology and Molecular, Cell and Developmental Biology, and National Phenotypic Screening Centre, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
PLoS One. 2024 Feb 20;19(2):e0297666. doi: 10.1371/journal.pone.0297666. eCollection 2024.
Male contraceptive options and infertility treatments are limited, and almost all innovation has been limited to updates to medically assisted reproduction protocols and methods. To accelerate the development of drugs that can either improve or inhibit fertility, we established a small molecule library as a toolbox for assay development and screening campaigns using human spermatozoa. We have profiled all compounds in the Sperm Toolbox in several automated high-throughput assays that measure stimulation or inhibition of sperm motility or the acrosome reaction. We have assayed motility under non-capacitating and capacitating conditions to distinguish between pathways operating under these different physiological states. We also assayed cell viability to ensure any effects on sperm function are specific. A key advantage of our studies is that all compounds are assayed together in the same experimental conditions, which allows quantitative comparisons of their effects in complementary functional assays. We have combined the resulting datasets to generate fingerprints of the Sperm Toolbox compounds on sperm function. The data are included in an on-line R-based app for convenient querying.
男性避孕药具和不孕治疗的选择有限,几乎所有的创新都局限于更新医学辅助生殖的方案和方法。为了加速能够改善或抑制生育能力的药物的研发,我们建立了一个小分子文库,作为使用人类精子进行检测开发和筛选活动的工具包。我们已经在多个自动化高通量检测中对精子工具包中的所有化合物进行了分析,这些检测可以测量精子运动或顶体反应的刺激或抑制作用。我们在非诱导和诱导条件下检测了运动能力,以区分在这些不同生理状态下运作的途径。我们还检测了细胞活力,以确保对精子功能的任何影响都是特异性的。我们研究的一个关键优势是,所有化合物都在相同的实验条件下一起进行检测,这允许对它们在互补功能检测中的影响进行定量比较。我们将得到的数据集组合起来,生成精子功能的精子工具包化合物指纹。数据包含在一个基于 R 的在线应用程序中,方便查询。