title: All-trans-retinoic acid regulates aquaporin-3 expression and related cellular membrane permeability in the human amniotic environment.
abstract: BACKGROUND
  The aquaporins (AQP1, 3, 8, 9 and 11) are known to be expressed, and involved in the transport of water and small molecules through fetal membranes. To exert these crucial functions, these AQPs have to be finely regulated. All-trans-retinoic acid (atRA) was previously found to regulate some genes in this environment, raising the question of whether these AQPs were regulated by atRA.
  
  
  METHODS
  Explants, and primary and established amniotic cells were cultured to determine which AQP were transcriptionally modified by atRA, using the qRT-PCR strategy. Immunohistochemistry and glycerol uptake tests were used to determine the impact of atRA on AQP protein expression and function. Specific agonists of retinoic acid receptors were used to identify the molecular mechanisms of AQP promoter activation. A classical gene AQP promoter study was also used to identify DR5 retinoic acid receptor elements (RAREs).
  
  
  RESULTS
  Beyond these AQPs, only one specific atRA-dependent increase in AQP3 transcripts and proteins level was established in amnion (not in chorion) and in related primary and established cells. We found three DR5-RAREs essential for inducing this transcriptional AQP3 through RARα. This transactivation of the AQP3 coding gene was functionally related to an increase of AQP3 permeability tests by a glycerol uptake assay.
  
  
  CONCLUSIONS
  Our data support an atRA regulatory model of AQP3 expression leading to an increased cellular permeability in the epithelial amniotic environment. We cast new light on AF regulation in healthy pregnancy, and advance new hypotheses for obstetrical complications linked to impairment of the retinoic signaling pathway.
authors.affiliation: Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.
authors.forename: C
authors.initials: C
authors.lastname: Prat
authors.affiliation: Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France; CHU Clermont-Ferrand, Biochemistry and Molecular Biology Department, F-63000 Clermont-Ferrand, France.
authors.forename: D
authors.initials: D
authors.lastname: Bouvier
authors.affiliation: Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.
authors.forename: A
authors.initials: A
authors.lastname: Comptour
authors.affiliation: Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France; CHU Clermont-Ferrand, Biochemistry and Molecular Biology Department, F-63000 Clermont-Ferrand, France.
authors.forename: G
authors.initials: G
authors.lastname: Marceau
authors.affiliation: Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, GReD, F-63000 Clermont-Ferrand, France.
authors.forename: C
authors.initials: C
authors.lastname: Belville
authors.affiliation: Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.
authors.forename: G
authors.initials: G
authors.lastname: Clairefond
authors.affiliation: Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France; CHU Clermont-Ferrand, Biochemistry and Molecular Biology Department, F-63000 Clermont-Ferrand, France.
authors.forename: P
authors.initials: P
authors.lastname: Blanc
authors.affiliation: Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France; CHU Clermont-Ferrand, Obstetrics and Gynecology Department, F-63000 Clermont-Ferrand, France.
authors.forename: D
authors.initials: D
authors.lastname: Gallot
authors.affiliation: Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.
authors.forename: L
authors.initials: L
authors.lastname: Blanchon
authors.affiliation: Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France; CHU Clermont-Ferrand, Biochemistry and Molecular Biology Department, F-63000 Clermont-Ferrand, France. Electronic address: vincent.sapin@udamail.fr.
authors.forename: V
authors.initials: V
authors.lastname: Sapin
mesh_terms: D000650:Amnion / Q000187:drug effects* / Q000378:metabolism; D051400:Aquaporin 3 / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D010539:Permeability / Q000187:drug effects; D011247:Pregnancy; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D051400:Aquaporin 3; D014212:Tretinoin
keywords: Amniotic fluid; Aquaporins; Fetal membranes; Retinoic acid