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Open Access 01-12-2015 | Research

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

Authors: Kanchan Vaswani, Hsiu-Wen Chan, Pali Verma, Marloes Dekker Nitert, Hassendrini N. Peiris, Ryan J. Wood-Bradley, James A. Armitage, Gregory E. Rice, Murray D. Mitchell

Published in: Reproductive Biology and Endocrinology | Issue 1/2015

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.

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Title: The rat placental renin-angiotensin system - a gestational gene expression study
Authors: Kanchan Vaswani
Hsiu-Wen Chan
Pali Verma
Marloes Dekker Nitert
Hassendrini N. Peiris
Ryan J. Wood-Bradley
James A. Armitage
Gregory E. Rice
Murray D. Mitchell
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Reproductive Biology and Endocrinology / Issue 1/2015
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/s12958-015-0088-y

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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