Project 461902

Infertility is a major health problem that affects 1 in 7 couples in the US and Canada, and male infertility affects up to half of these couples. Between 40-50% of male infertility cases remain unexplained, illustrating our poor knowledge of male reproductive biology. The testis produces immature sperm that then transit in the epididymis, a small organ formed by a single long tubule (as long as 7 meters in men). Male infertility can be caused by sperm that cannot reach and fertilize an oocyte. Sperm acquire these crucial functions in the epididymis. However, the cellular mechanisms responsible for the acquisition of sperm fertilizing competence in the epididymis remain poorly characterized. Our proposed study aims at filling this gap by elucidating how an optimal environment in the epididymis is established for the maturation and viability of spermatozoa. The epididymal tubule cavity is lined by specialized "epithelial" cells that work together to establish a unique acidic environment that is essential for the proper maturation of spermatozoa, and defects in acid/base balance in this organ impairs the ability of a man to have children. Our overall objective is to identify new intercellular communication networks that epididymal epithelial cells use to detect and respond to local stimuli to modulate their environment. Our long-term goal is to provide actionable information that could eventually be translated into clinical advances for the diagnosis and treatment of male infertility associated with dysfunctions of the post-testicular male reproductive tract. Male infertility has a strong emotional impact for couples who wish to have children. We believe that our study will provide alternative options to in vitro fertilization (IVF), one of the very few options available to these couples. In addition, IVF is associated with a number of potential risks to the woman, and our study will not only help men's health, but will also ultimately help women's health.