A Bicarbonate Boost to Fertility

Abstract

Wang et al. linked cystic fibrosis transmembrane conductance regulator (CFTR)-mediated bicarbonate transport in endometrial epithelia to sperm capacitation. Sperm capacitation, which depends on environmental factors in the female reproductive tract, is a process critical to the ability of sperm to fertilize eggs. Cystic fibrosis is a genetic disease associated with mutations of CFTR, a cyclic adenosine monophosphate (cAMP)-activated anion channel found in epithelial tissues. The ensuing defect in chloride secretion, and consequent production of thick sticky mucus, leads to impaired respiratory and digestive function and has been presumed to underlie reduced fertility in women with cystic fibrosis. Although CFTR also mediates bicarbonate secretion, and bicarbonate has been associated--through activation of adenylyl cyclase--with sperm capacitation in vitro (see Sutton et al. ), the physiological significance of these observations has been unclear. Wang et al. used electrophysiological, pharmacological, and antisense analysis, together with fluorimetric measurements of intracellular pH and ion substitution, to implicate CFTR in bicarbonate transport across mouse endometrial epithelial cell cultures. Capacitation of mouse sperm was enhanced by conditioned medium from endometrial epithelial cultures or by bicarbonate. The ability of conditioned medium to enhance sperm capacitation was inhibited by antisense against CFTR. Conditioned medium from a pancreatic duct cell line that expressed CFTR promoted capacitation, whereas medium from a pancreatic line expressing a mutant CFTR that was defective in bicarbonate secretion did not. Capacitation by the latter was rescued by bicarbonate, or by transfecting cells with wild-type CFTR. These data point to a physiological role for bicarbonate transport by CFTR, as well as support a role for bicarbonate in mediating capacitation--and thereby contributing to fertility--in vivo. X. F. Wang, C. X. Zhou, Q. X. Shi, Y. Y. Yuan, M. K. Yu, L. C. Ajonuma, L. S. Ho, P. S. Lo, L. L. Tsang, Y. Liu, S. Y. Lam, L. N. Chan, W. C. Zhao, Y. W. Chung, H. C. Chan, Involvement of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm. Nat. Cell Biol . 5 , 902-906 (2003). [Online Journal] K. A. Sutton, M. K. Jungnickel, H. M. Florman, Of fertility, cystic fibrosis and the bicarbonate ion. Nat. Cell Biol . 5 , 857-859 (2003). [Online Journal]