title: Utero-placental expression of angiotensin-(1-7) and ACE2 in the pregnant guinea-pig.
abstract: BACKGROUND
  In humans, trophoblast invasion, vascular remodeling and placental development are critical to determine the fate of pregnancy. Since guinea-pigs (GP) and humans share common pregnancy features including extensive trophoblast invasion, transformation of the uterine spiral arteries and a haemomonochorial placenta, the GP animal model was deemed suitable to extend our knowledge on the spatio-temporal immunoreactive expression of the vasodilator arpeptide of the renin-angiotensin system, angiotensin-(1-7) [Ang-(1-7)] and its main generating enzyme, angiotensin converting enzyme 2 (ACE2).
  
  
  METHODS
  Utero-placental units were collected in days 15, 20, 40 and 60 of a 64-67 day long pregnancy in 25 Pirbright GP. Ang-(1-7) and ACE2 expression in utero-placental units were evaluated by immunohistochemistry.
  
  
  RESULTS
  Ang-(1-7) and ACE2 were detected in the endothelium and syncytiotrophoblast of the labyrinthine placenta, interlobium, subplacenta, giant cells, syncytial sprouts, syncytial streamers, and myometrium throughout pregnancy. In late pregnancy, perivascular or intramural trophoblasts in spiral and mesometrial arteries expressed both factors. Immunoreactive Ang-(1-7) and ACE2 were present in decidua and in the vascular smooth muscle of spiral, myometrial and mesometrial arteries, which also express kallikrein (Kal), the bradykinin receptor 2 (B2R), vascular endothelial growth factor (VEGF) and its type 2 receptor (KDR), but no endothelial nitric oxide synthase (eNOS). In addition, the signal of Ang-(1-7) and ACE2 was especially remarkable in giant cells, which also show Kal, B2R. eNOS, VEGF and KDR.
  
  
  CONCLUSIONS
  The spatio-temporal expression of Ang-(1-7) and ACE2 in GP, similar to that of humans, supports a relevant evolutionary conserved function of Ang-(1-7) and ACE2 in decidualization, trophoblast invasion, vascular remodeling and placental flow regulation, as well as the validity of the GP model to understand the local adaptations of pregnancy. It also integrates Ang-(1-7) to the utero-placental vasodilatory network. However, its antiangiogenic effect may counterbalance the proangiogenic activity of some of the other vasodilator components.
authors: Centro de Investigaciones Médicas y Departamento de Nefrología, Escuela de Medicina, Pontificia Universidad Católica, Santiago, Chile. gvaldesst@gmail.com
authors: Gloria
authors: G
authors: Valdés
authors: Jenny
authors: J
authors: Corthorn
authors: Manish S
authors: MS
authors: Bharadwaj
authors: Janae
authors: J
authors: Joyner
authors: Daniela
authors: D
authors: Schneider
authors: K Bridget
authors: KB
authors: Brosnihan
mesh_terms: D000803:Angiotensin I / Q000032:analysis*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D003656:Decidua / Q000737:chemistry; D042783:Endothelial Cells / Q000737:chemistry; D005260:Female; D005865:Gestational Age; D006168:Guinea Pigs; D007150:Immunohistochemistry; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D010446:Peptide Fragments / Q000032:analysis*; D007703:Peptidyl-Dipeptidase A / Q000032:analysis*; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D014327:Trophoblasts / Q000737:chemistry; D055988:Uterine Artery / Q000737:chemistry; D014599:Uterus / Q000098:blood supply / Q000737:chemistry*
chemical_list: D010446:Peptide Fragments; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)