A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activity

Area of Science:

• Reproductive biology
• Drug discovery
• Andrology

Background:

• A significant need exists for novel male contraceptive methods.
• Current male contraceptive development is hindered by a lack of validated targets and effective high-throughput screening systems.

Purpose of the Study:

• To develop a fully-automated robotic screening platform for evaluating compounds impacting human sperm function.
• To accelerate the discovery of new male contraceptive agents by screening a large library of existing drugs.

Main Methods:

• A high-throughput, automated robotic platform was created to quantitatively assess compound activity on human sperm motility and acrosome reaction.
• The ReFRAME repurposing library, containing 12,000 molecules, was screened using this platform.

Main Results:

• Several compounds were identified that exhibit potent inhibition of sperm motility.
• These findings suggest novel drug candidates and potential new targets for male contraception.

Conclusions:

• The developed screening platform is effective for identifying male contraceptive leads.
• This approach facilitates major drug discovery programs and can uncover new aspects of human sperm biology.