Involvement of CFTR in oviductal HCO3- secretion and its effect on soluble adenylate cyclase-dependent early embryo development  

Oleh:

Min Hui, Chen ; Hui, Chen ; Zhen, Zhou

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Human Reproduction vol. 25 no. 07 (Jul. 2010), page 1744-1754.
Topik: CFTR; HCO3-; oviduct; soluble adenylate cyclase; embryo development

Ketersediaan

Perpustakaan FK Nomor Panggil: H07.K.2010.03 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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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.

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