The rat placental renin-angiotensin system - a gestational gene expression study

Vaswani, Kanchan, Chan, Hsiu-Wen, Verma, Pali, Nitert, Marloes Dekker, Peiris, Hassendrini N., Wood-Bradley, Ryan J., Armitage, James A., Rice, Gregory E. and Mitchell, Murray D. (2015) The rat placental renin-angiotensin system - a gestational gene expression study. Reproductive Biology and Endocrinology, 13 89: 1-10. doi:10.1186/s12958-015-0088-y

Author Vaswani, Kanchan
Chan, Hsiu-Wen
Verma, Pali
Nitert, Marloes Dekker
Peiris, Hassendrini N.
Wood-Bradley, Ryan J.
Armitage, James A.
Rice, Gregory E.
Mitchell, Murray D.
Title The rat placental renin-angiotensin system - a gestational gene expression study
Journal name Reproductive Biology and Endocrinology   Check publisher's open access policy
ISSN 1477-7827
Publication date 2015-08-12
Sub-type Article (original research)
DOI 10.1186/s12958-015-0088-y
Open Access Status DOI
Volume 13
Issue 89
Start page 1
End page 10
Total pages 10
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2016
Language eng
Formatted abstract
Background:  The placenta is an essential organ that provides nutrients and oxygen to the developing fetus and removes toxic waste products from the fetal circulation. Maintaining placental blood osmotic pressure and blood flow is crucial for viable offspring. The renin-angiotensin system (RAS) in the placenta is a key player in the regulation of maternal-fetal blood flow during pregnancy. Therefore, the aim of this study was to determine if RAS genes are differentially expressed in mid to late gestation in rat placenta.

Methods:  Whole placental tissue samples from pregnant Sprague Dawley rats at embryonic (E) days 14.25, 15.25, 17.25 and 20 (n = 6 for each gestational age) were used for genome-wide gene expression by microarray. RAS genes with expression differences of >2 fold were further analyzed. Quantitative Real-Time PCR (qPCR) was performed on independent samples to confirm and validate microarray data. Immunohistochemisty and Western blotting were performed on a differentially expressed novel RAS pathway gene (ANPEP).

Results:  Six out of 17 genes of the RAS pathway were differentially expressed at different gestational ages. Gene expression of four genes (Angiotensin converting enzyme (Ace), angiotensin converting enzyme 2 (Ace2), membrane metalloendopeptidase (Mme) and angiotensin II receptor 1A (Agtr1a)) were significantly upregulated at E20 whereas two others (Thimet oligopeptidase 1 (Thop1) and Alanyl aminopeptidase (Anpep)) were downregulated at E20 prior to the onset of labour. These changes were confirmed by qPCR. Western blots revealed no overall differences in ANPEP protein expression in the placentae. Immunohistochemical studies, however, indicated that the localization of ANPEP differed at E17.25 and E20 as ANPEP localization in the giant trophoblast cell of the junctional zone was no longer detectable at E20.

Conclusions:  The current study investigated the expression of members of the RAS pathway in rat placentae and observed significantly altered expression of 6 RAS genes at 4 gestational ages. These findings present the need for further comprehensive investigation of RAS genes in normal and complicated pregnancies.
Keyword Gestation
Renin-Angiotensin System
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
School of Medicine Publications
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