Title:CFTR Regulation of Aquaporin-Mediated Water Transport: A Target in Male Fertility
Volume: 16
Issue: 9
Author(s): Marco G. Alves, Rosália Sá, Tito T. Jesus, Mário Sousa and Pedro F. Oliveira
Affiliation:
Keywords:
Aquaporins, CFTR, male reproductive tract, male fertility, spermatogenesis.
Abstract: 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.
