Involvement of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel expressed in a wide variety of epithelial cells, mutations of which are responsible for the hallmark defective chloride secretion observed in cystic fibrosis (CF). Although CFTR has been implicated in bicarbonate secretion, its ability to directly mediate bicarbonate secretion of any physiological significance has not been shown. We demonstrate here that endometrial epithelial cells possess a CFTR-mediated bicarbonate transport mechanism. Co-culture of sperm with endometrial cells treated with antisense oligonucleotide against CFTR, or with bicarbonate secretion-defective CF epithelial cells, resulted in lower sperm capacitation and egg-fertilizing ability. These results are consistent with a critical role of CFTR in controlling uterine bicarbonate secretion and the fertilizing capacity of sperm, providing a link between defective CFTR and lower female fertility in CF.

Activation of GABAAReceptor/Cl−Channel and Capacitation in Rat Spermatozoa: HCO3−and Cl−are Essential

“…This is consistent with the results obtained in earlier studies using spermatozoa from various species [Lee and Storey 1986;Shi and Roldan 1995a;Visconti et al 1995;. Our previous studies have demonstrated that the involvement of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm were important [Wang et al 2003]. Previously, some studies proposed that a crucial role of the CFTR is to conduct both Cl À and HCO 3 À [Poulsen et al 1994;Reddy and Quinton 2001].…”

“…This has been considered to be indicative of the completion of capacitation [Florman and Babcock 1991;Jaiswal and Eisenbach 2002;Visconti et al, 1998;Yanagimachi 1994]. Therefore, the sum of ''B þ AR'' patterns of spermatozoa during incubation that undergo capacitation is generally taken as an indicator for completion of capacitation [Barboni et al 1995;DasGupta et al 1994;Visconti et al 1998;Wang et al 2003;Xu et al 2007]. Although there was no significant difference (P 4 0.05) observed in the B pattern between GABAtreated ( Fig.…”

“…The optimal concentration of HCO 3 À varies from species to species but it plays a central role in sperm capacitation [Lee and Storey 1986;Neill and Olds-Clarke 1987;Shi and Roldan 1995a;Visconti et al 1995;Wang et al 2003]. Recent studies have shown that bicarbonate directly stimulates the soluble adenylyl cyclase (sAC) activity of spermatozoa.…”

NYD-SP27, a novel intrinsic decapacitation factor in sperm

“…A number of capacitation factors (such as HCO 3 -) and decapacitation factors [1,2] have been implicated in these processes. Although the presence of decapacitation factors in the seminal plasma has been reported, no such factor intrinsic to the sperm has been identified.…”

“…Mammalian spermatozoa cannot undergo fertilization without proper activation, termed 'capacitation', in the female tract [1]. During capacitation, extensive changes occur in various sperm compartments.…”