CFTR Regulation of Aquaporin-Mediated Water Transport: A Target in Male Fertility

The formation of competent spermatozoa is associated with the movement of large quantities of water and electrolytes in the various tissues and luminal fluids of the male reproductive tract. The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated Cl(-) and HCO3(-) membrane transporter. CFTR gene mutations cause cystic fibrosis (CF), the most common lethal genetic disease in Caucasians. Of note, one hallmark in CF is male infertility. Indeed, mutations of CFTR gene cause abnormal production of germ cells and a reduction in germ cell quality and number. Compelling evidence illustrates that CFTR is involved in several pivotal processes for male fertility, including spermatogenesis and sperm capacitation. Recent studies show that CFTR acts as a molecular partner of specific water channels, known as aquaporins, in somatic testicular cells. Aquaporins are water-selective channels that enable high permeability fluxes of water across plasma membranes. In the male reproductive tract, water movements and ion concentrations are determinants for the male reproductive function. Therefore, aquaporins expression and function play a key role in male fertility. Herein we present an overview of the expression and function of CFTR in the male reproductive tract, highlighting the reproductive outcomes in male carriers of CFTR mutations and CF couples. We also present an up-to-date discussion on the expression and role of aquaporins in the male reproductive tract. Finally, we discuss the regulation of aquaporin-mediated water transport by CFTR in the male reproductive tract and its implication for male fertility.