title: Involvement of Cl(-)/HCO3(-) exchanger SLC26A3 and SLC26A6 in preimplantation embryo cleavage.
abstract: Bicarbonate (HCO3(-)) is essential for preimplantation embryo development. However, the mechanism underlying the HCO3(-) transport into the embryo remains elusive. In the present study, we examined the possible involvement of Cl(-)/HCO3(-) exchanger in mediating HCO3(-) transport into the embryo. Our results showed that depletion of extracellular Cl(-), even in the presence of HCO3(-), suppressed embryo cleavage in a concentration-dependent manner. Cleavage-associated HCO3(-)-dependent events, including increase of intracellular pH, upregulation of miR-125b and downregulation of p53, also required Cl(-). We further showed that Cl(-)/HCO3(-) exchanger solute carrier family 26 (SLC26) A3 and A6 were expressed at 2-cell through blastocyst stage. Blocking individual exchanger's activity by inhibitors or gene knockdown differentially decreased embryo cleavage and inhibited HCO3(-)-dependent events, while inhibiting/knocking down both produced an additive effect to an extent similar to that observed when CFTR was inhibited. These results indicate the involvement of SLC26A3 and A6 in transporting HCO3(-) essential for embryo cleavage, possibly working in concert with CFTR through a Cl(-) recycling pathway. The present study sheds light into our understanding of molecular mechanisms regulating embryo cleavage by the female reproductive tract.
authors.affiliation: Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Yong Chao
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong SAR, China.
authors.forename: Kin Lam
authors.initials: KL
authors.lastname: Fok
authors.affiliation: Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Ying Hui
authors.initials: YH
authors.lastname: Ye
authors.affiliation: Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Zheng Yun
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Xin Mei
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.|The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: He Feng
authors.initials: HF
authors.lastname: Huang
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong SAR, China.
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001755:Blastocyst / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D011247:Pregnancy; D000076988:Sulfate Transporters; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D001639:Bicarbonates; C505032:CFTR protein, human; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; C531888:MIRN125 microRNA, human; D026901:Membrane Transport Proteins; D035683:MicroRNAs; C081011:SLC26A3 protein, human; C439529:SLC26A6 protein, human; D000076988:Sulfate Transporters; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019005:Cystic Fibrosis Transmembrane Conductance Regulator