Involvement of CFTR in oviductal HCO-3secretion and its effect on soluble adenylate cyclase-dependent early embryo development

Min Hui Chen, Hui Chen, Zhen Zhou, Yechun Ruan, Hau Yan Wong, Yong Chao Lu, Jing Hui Guo, Yiu Wa Chung, Ping Bo Huang, He Feng Huang, Wen Liang Zhou, Hsiao Chang Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

28 Citations (Scopus)

Abstract

Background: The cystic fibrosis transmembrane conductance regulator (CFTR) plays a critical role in electrolyte and fluid transport in epithelial cells, and women with cystic fibrosis (CF), caused by CFTR gene mutations, have a higher incidence of infertility. Methods: In the present study, we investigated the expression of CFTR in porcine oviduct and its functional role in oviductal HCO3-secretion and embryo development with RT-PCR, western blot, patch-clamp, short-circuit current (Isc), pH measurement and embryo culture. Results: RT-PCR and western blot analysis showed the expression of CFTR mRNA and protein in the oviduct with its localization demonstrated by immunohistochemstry. The whole-cell patch-clamp recording revealed a forskolin (FSK)-activated current with electrophysiological and pharmacological characteristics of CFTR. The Isc measurement showed that FSK-stimulated an increase in the Isc, which could be significantly reduced by CFTR inhibitor or removal of both CO2 and HCO3-. pH measurement showed a FSK stimulated alkalization at the apical surface, which could be inhibited by CFTR inhibitor, indicating CFTR-mediated HCO3-secretion. Mouse embryo development from 2-cell to morula or blastocyst stage was significantly inhibited in the absence of HCO3-or when co-cultured with HCO3-secretion-deficient CFTR mutant cells as compared with the wild-type. RT-PCR, western blot and immunostaining showed the expression of soluble adenylate cyclase (sAC), the known HCO3-sensor, in embryos. Treatment with its inhibitors, 2-hydroxyestradiol and KH7, prevented the HCO3-dependent embryo development. Conclusion: The present Results: suggest that CFTR-mediated oviductal HCO3-secretion may be vital for sAC-dependent early embryo development, a defect of which may contribute to the reduced fertility seen in women with CF.
Original languageEnglish
Pages (from-to)1744-1754
Number of pages11
JournalHuman Reproduction
Volume25
Issue number7
DOIs
Publication statusPublished - 1 Jul 2010
Externally publishedYes

Keywords

  • CFTR
  • embryo development
  • HCO - 3
  • oviduct
  • soluble adenylate cyclase

ASJC Scopus subject areas

  • Reproductive Medicine
  • Rehabilitation
  • Obstetrics and Gynaecology

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