title: The effects of gestational age and maternal hypoxia on the placental renin angiotensin system in the mouse.
abstract: BACKGROUND
  The renin angiotensin system (RAS) is an important mediator of placental development. However, a comprehensive expression profile for 8 key components of the placental RAS throughout murine gestation has not been performed. Furthermore, maternal hypoxia induces dysregulation of RAS expression in fetal tissues but the effects on the murine placental RAS are less well known.
  
  
  METHODS
  Placentas were collected from male and female CD1 mouse fetuses at seven gestational ages for qPCR analysis of Agt, Ren1, Atp6ap2, Ace, Ace2, Agtr1a, Agtr2 and Mas1. mRNA localisation of Agtr1 and Mas1 and protein localisation of ACE and ACE2 was determined at E18.5. To determine the effects of maternal hypoxia on the placental RAS, mice were housed in 12% oxygen from E14.5-E18.5 and placentas examined at E18.5.
  
  
  RESULTS
  All RAS genes were expressed in the placenta throughout pregnancy and expression varied with fetal sex and age. Agtr1 was expressed within the labyrinth while Mas1 was expressed within the intraplacental yolk sac. ACE and ACE2 were localised to both labyrinth and junctional zones. In response to maternal hypoxia the expression of Agt, Ace and Ace2 was decreased but expression of Agtr1a was increased. Ace and Agtr1a mRNA levels were affected to a greater extent in females compared to males.
  
  
  CONCLUSIONS
  Collectively, the location within the placenta as well as the expression profiles identified, support a role for the placental RAS in labyrinth development. The placental RAS is disturbed by maternal hypoxia in a sexually dimorphic manner and may contribute to impairment of placental vascular development.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: J S M
authors.initials: JS
authors.lastname: Cuffe
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: Walton
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: S E
authors.initials: SE
authors.lastname: Steane
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: R R
authors.initials: RR
authors.lastname: Singh
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: D G
authors.initials: DG
authors.lastname: Simmons
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia. Electronic address: k.moritz@uq.edu.au.
authors.forename: K M
authors.initials: KM
authors.lastname: Moritz
mesh_terms: D000818:Animals; D005260:Female; D005865:Gestational Age; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D051379:Mice; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012084:Renin-Angiotensin System; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor; C000715470:MAS1 protein, human; C000715471:Mas1 protein, mouse
keywords: Hypoxia; Placenta; Renin angiotensin system