The effects of gestational age and maternal hypoxia on the placental renin angiotensin system in the mouse

Cuffe, J. S. M., Walton, S. L., Steane, S. E., Singh, R. R., Simmons, D. G. and Moritz, K. M. (2014) The effects of gestational age and maternal hypoxia on the placental renin angiotensin system in the mouse. Placenta, 35 11: 953-961. doi:10.1016/j.placenta.2014.09.004

Author Cuffe, J. S. M.
Walton, S. L.
Steane, S. E.
Singh, R. R.
Simmons, D. G.
Moritz, K. M.
Title The effects of gestational age and maternal hypoxia on the placental renin angiotensin system in the mouse
Journal name Placenta   Check publisher's open access policy
ISSN 1532-3102
Publication date 2014-11-01
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.placenta.2014.09.004
Open Access Status
Volume 35
Issue 11
Start page 953
End page 961
Total pages 9
Place of publication London United Kingdom
Publisher Elsevier
Language eng
Formatted abstract

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.


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.


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.


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.
Keyword Placenta
Renin angiotensin system
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1009338
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Alliance for Agriculture and Food Innovation
Official 2015 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
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