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Related Concept Videos

Sperm Transport01:15

Sperm Transport

The journey of sperm from its origin to the point of ejaculation begins within the seminiferous tubules of the testis. Here, Sertoli cells produce fluid that propels non-motile sperm through a series of conduits, starting with the straight tubules leading to the rete testis. This interconnected network of tubules acts as the initial pathway for sperm, guiding them into the efferent ductules and then into the epididymis for maturation.
The maturation phase occurs in the epididymis, where sperm...

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Compounds enhancing human sperm motility identified using a high-throughput phenotypic screening platform.

Franz S Gruber1, Zoe C Johnston2, Neil R Norcross3

  • 1National Phenotypic Screening Centre, School of Life Sciences, University of Dundee, Dundee, UK.

Human Reproduction (Oxford, England)
|January 20, 2022
PubMed
Summary
This summary is machine-generated.

A high-throughput screening platform identified numerous compounds that can enhance sperm motility, offering a promising starting point for male fertility drug discovery and advancing our understanding of sperm function.

Keywords:
drug discoveryhigh-throughput screeningsperm motilityspermatozoasubfertility

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Area of Science:

  • Reproductive Biology
  • Pharmacology
  • Drug Discovery

Background:

  • Previous efforts to discover small molecules for modulating sperm function have not utilized high-throughput screening (HTS) technology.
  • HTS offers a novel approach to systematically screen compound libraries for potential male fertility agents.

Purpose of the Study:

  • To investigate the utility of a high-throughput screening platform in identifying compounds that enhance sperm motility.
  • To discover novel small molecules that could serve as starting points for male fertility drug development.

Main Methods:

  • Utilized a phenotypic screening assay involving approximately 17,000 compounds from diverse libraries.
  • Spermatozoa from healthy donors were incubated with compounds in 384-well plates to assess effects on motility.
  • Dose-response experiments were conducted on confirmed hits to validate their efficacy.

Main Results:

  • Identified 105 compounds that significantly enhanced sperm motility compared to controls.
  • Discovered that phosphodiesterase inhibitors, particularly PDE10A inhibitors, were a major class of compounds affecting motility.
  • Identified compounds related to GABA signaling as novel enhancers of human sperm motility.

Conclusions:

  • The high-throughput screening platform successfully identified a substantial number of compounds that increase sperm motility.
  • These findings provide a valuable resource for male fertility research and highlight potential lead compounds for medicinal chemistry programs.
  • Further in vitro and in vivo studies are necessary to fully characterize compound activity, mechanisms, and potential therapeutic applications.