High-Throughput Screening for Novel Contraceptive Agents

Francisco Diaz of Pennsylvania State University in the U.S. will develop a high-throughput screening method to identify compounds that can block two biological events essential for female fertility without affecting ovulation or hormone production in order to identify new contraceptives with fewer side effects. These two events, which occur at the same time, are cumulus expansion, whereby cumulus cells release from the oocyte to enable it to enter the oviduct, and oocyte maturation, whereby the oocyte divides to produce the egg and a smaller polar body. They will extract cumulus oocyte complexes from primed female mice and apply them to a microwell array prototype that will contain 1,024 wells coated with different test compounds and connected in groups by microfluidic channels. Oocytes in the wells will be stimulated to undergo first cumulus expansion, and, after removal of cumulus cells, oocyte maturation. The ability of each compound to inhibit each step will be assessed by automated inverted microscopy. They will first optimize their platform using known inhibitors and then test it using a library of 1,200 FDA approved molecules.