The role of CFTR in spermatogenesis and sperm quality

Cystic fibrosis (CF) is primarily recognized for its severe systemic effects, especially in the lungs, pancreas and digestive tract. Thus, the effect of CF transmembrane conductance regulator (CFTR) dysfunction on male fertility has been relatively overlooked despite its important roles in spermatogenesis orchestration and spermatozoa function. CFTR has physiological functions as a chloride and bicarbonate channel and a role in regulating water movement. CFTR participates in spermatogenesis, and evidence suggests its involvement in seminiferous intratubular fluid control, maintenance of the blood-testis barrier, and improvement in follicle-stimulating hormone signalling, among other functions. Emerging evidence also suggests that CFTR variant carriers, typically considered to be healthy, have reduced sperm quality. Diminished CFTR expression has been observed in spermatozoa from men with various sperm quality abnormalities (teratozoospermia, asthenozoospermia and oligozoospermia), and correlates positively with sperm motility and morphology. CFTR is thought to be involved in sperm capacitation and osmoregulation via interactions with ion and water channels. Advances in CF therapy, such as CFTR modulators, gene therapy and liposome-mediated CFTR delivery, might affect CFTR's role in sperm function and could potentially be applied to improve the fertility of individuals with CFTR dysfunction.