title: Regulatory mechanism underlying cyclic changes in mouse uterine bicarbonate secretion: role of estrogen.
abstract: Our previous study has demonstrated that bicarbonate in the uterine fluid plays an indispensable role in sperm capacitation. However, the cellular mechanisms underlying the formation of bicarbonate-rich uterine fluid and the regulatory mechanism remained largely unknown. In this study, the expression profiles of bicarbonate transport/production proteins, the cystic fibrosis transmembrane conductance regulator (CFTR), SLC26A6, carbonic anhydrase 2 (CAR2, CA2) and CAR12 (CA12), throughout the estrous cycle, were examined in the mouse uterus by western blot. The results showed that the maximum expression levels of the proteins examined were observed at estrus. Luminal surface pH measurements showed that the resting uterine surface pH at estrus was significantly higher than that at diestrus, which could be reduced significantly by CFTR blocker, diphenylamine-2,2'-dicarboxylic acid, SLC26A6 inhibitor, 4',4'-diisothiocyanostilbene-2',2'-disulfonic acid, and CA inhibitor, acetazolamide. In ovariectomized mice and primary culture of endometrial epithelial cells, estrogen could upregulate CFTR, SLC26A6, CAR2, and CAR12 expression with a corresponding increase in the bicarbonate-dependent short-circuit current (I(sc)) and endometrial surface pH. The present results have demonstrated dynamic changes in uterine bicarbonate secretion and expression of the proteins involved in bicarbonate secretion during the estrous cycle and suggested a novel role of estrogen in regulating uterine bicarbonate transport, which may be important for successful reproduction.
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, People's Republic of China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: He
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Connie Hau Yan
authors.initials: CH
authors.lastname: Wong
authors.forename: Lai Ling
authors.initials: LL
authors.lastname: Tsang
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D030762:Estrous Cycle / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D051379:Mice; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D000076988:Sulfate Transporters; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D017920:Antiporters; D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D004965:Estrogen Antagonists; D004967:Estrogens; D007527:Isoenzymes; D011960:Receptors, Estrogen; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002256:Carbonic Anhydrases