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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.

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Figure 1: Involvement of CFTR in mediating cAMP-stimulated bicarbonate extrusion in mouse endometrial epithelial cells.
Figure 2: Involvement of CFTR in uterine bicarbonate secretion.
Figure 3: CFTR-suppressed endometrial epithelial cells decreases sperm capacitation and egg-fertilizing ability.
Figure 4: Defective bicarbonate-secreting CF cells decreases sperm capacitation and egg-fertilizing ability.

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Acknowledgements

The work was supported by the Strategic Program of the Chinese University of Hong Kong, Distinguished Young Investigator Fund by National Science Foundation of China (to H.C.C.) and National 973 Project of China.

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Correspondence to Hsiao Chang Chan.

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Wang, X., Zhou, C., Shi, Q. et al. Involvement of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm. Nat Cell Biol 5, 902–906 (2003). https://doi.org/10.1038/ncb1047

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