Hayley Dickinson of Monash University in Australia will evaluate the spiny mouse, which is the only rodent that naturally menstruates, as a new animal model for developing and testing contraceptives. Menstruation is an essential feature of human reproduction, and is regulated by hormonal contraceptives. However, current contraceptives like the contraceptive pill can cause side effects such as anxiety and low libido. A small animal model that mimics human menstruation would be valuable for testing new contraceptives that have fewer side effects. The menstrual cycle of the spiny mouse, like that in humans, involves progesterone production from a transient endocrine gland. These mice also display cycles of anxiety behavior similar to premenstrual tension. They will validate it as a model for contraceptive drug discovery by analyzing the effects of current human contraceptives on fertility, hormonal profiles, vaginal cytology, and behavior.

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.

Randall Peterson of the University of Utah in the U.S. will develop a zebrafish model for high-throughput screens to identify compounds that inhibit the formation of gametes, i.e., sperm or eggs, (gametogenesis), which could lead to male and female contraceptives that last for weeks or months after only a single dose. They will generate transgenic zebrafish lines that express a selection of four fluorescently-labeled markers for different stages of gametogenesis that can be rapidly quantified to measure the effects of candidate compounds on blocking gamete production. The suitability of these zebrafish lines for high-throughput multi-well compound screens will be tested using known inhibitors of gametogenesis.

Maria Gallo of Ohio State University in the U.S. will adapt a validated computer-based psychological test known as the Implicit Association Test to measure the true opinions of women in Vietnam on hormonal contraceptives in order to encourage use. Vietnam has one of the highest rates of abortion worldwide. Although hormonal contraceptives are available, it is thought that many women are worried about using them and instead use alternative methods that are generally less effective. Finding out exactly what these women think about hormonal contraceptives in order to dispel any myths is challenging because many people either don’t say or don’t realize what they think for a variety of social and psychological reasons. The Implicit Association Test overcomes this challenge by measuring the strength of the associations an individual makes between two pairs of contrasting concepts based on speed. They will adapt the test to determine opinions about the intrauterine device and oral contraception by measuring the strength of their associations with good or bad, and natural or unnatural. This will be tested using a cross-sectional study of 500 non-pregnant females.