Abstract
Nearly 50% of the pregnancies worldwide are unintended, which causes 80,000 maternal deaths every year due to unsafe abortions. This indicates there is an unmet need for new male contraceptive methods, which would facilitate family planning and promote family health. EPPIN (Epididymal protease inhibitor) is a promising target for male contraception due to its crucial role on reproduction and druggable properties. In humans, EPPIN is present on the surface of ejaculate spermatozoa, where it plays a role on sperm motility. In vitro studies showed that anti-EPPIN antibodies decreased progressive motility of human spermatozoa, indicating that sperm function can be inhibited by the pharmacological manipulation of EPPIN. To further develop EPPIN as a target for male contraceptive drugs a transition from in vitro to in vivo models is required. This would allow a deeper understanding on its physiological roles and facilitate the rational design of new EPPIN-binding drugs. Here, we propose to investigate the role of Eppin gene in the male fertility using the mouse as an experimental model. We will perform functional, molecular and protein-protein interaction assays to advance our knowledge regarding EPPIN´s role in reproduction and its potential as a therapeutic target for male contraception. Our results will provide the basis for the development of an animal model to evaluate the in vivo efficacy of male contraceptive drugs that inhibit sperm motility by binding to EPPIN, to shed light into the basic mechanisms by which EPPIN controls male fertility in vivo, and to provide new insights into the evolution of EPPIN gene. Our proposal has relevance and potential to innovate in the field of Pharmacology. (AU)
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