title: Estradiol modulates Na(+) -dependent HCO3 (-) transporters altering intracellular pH and ion transport in human Sertoli cells: A role on male fertility?
abstract: BACKGROUND
  Infertile men often present deregulation of serum estrogen levels. Notably, high levels of estradiol (E2) are associated with low sperm production and quality. Sertoli cells (SCs) are responsible for spermatogenesis maintenance and are major targets for the hormonal signalling that regulates this complex process.
  
  
  RESULTS
  In this study, we used primary cultures of human SCs and studied the localisation, expression and functionality of the Na(+) -dependent HCO3 (-) transporters by confocal microscopy, immunoblot, epifluorescence and voltage clamp after 24 h of exposure to E2 (100 nM). All studied transporters were identified in human SCs. In E2-treated human SCs, there was an increase in NBCn1, NBCe1 and NDCBE protein levels, as well as an increase in intracellular pH and a decrease in transcellular transport.
  
  
  CONCLUSIONS
  We report an association between increased levels of E2 and the expression/function of Na(+) -dependent HCO3 (-) transporters in human SCs. Our results provide new evidence on the mechanisms by which E2 can regulate SCs physiology and consequently spermatogenesis. These mechanisms may have an influence on male reproductive potential and help to explain male infertility conditions associated with estrogen deregulation.
  
  
  CONCLUSIONS
  Exposure to E2 increased human SCs intracellular pH. E2 is a modulator of ionic transcellular transport in human SCs.
authors.affiliation: Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.
authors.forename: Raquel L
authors.initials: RL
authors.lastname: Bernardino
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Costa
authors.affiliation: Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.|CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Ana D
authors.initials: AD
authors.lastname: Martins
authors.affiliation: Centre for Reproductive Genetics Prof. Alberto Barros, Porto, Portugal.
authors.forename: Joaquina
authors.initials: J
authors.lastname: Silva
authors.affiliation: Centre for Reproductive Genetics Prof. Alberto Barros, Porto, Portugal.|Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal.|I3S, Institute for Innovation and Health Research, University of Porto, Porto, Portugal.
authors.forename: Alberto
authors.initials: A
authors.lastname: Barros
authors.affiliation: Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.|Centre for Reproductive Genetics Prof. Alberto Barros, Porto, Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Sousa
authors.affiliation: Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.
authors.forename: Rosália
authors.initials: R
authors.lastname: Sá
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Marco G
authors.initials: MG
authors.lastname: Alves
authors.affiliation: Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.|I3S, Institute for Innovation and Health Research, University of Porto, Porto, Portugal.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Oliveira
mesh_terms: D001639:Bicarbonates / Q000378:metabolism; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005298:Fertility / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D027982:Sodium-Bicarbonate Symporters; D004958:Estradiol; D012964:Sodium
keywords: Electron/light microscopy; Membrane transport; Reproductive biology; Transporters