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Title: Sildenafil Therapy Normalizes the Aberrant Metabolomic Profile in the Comt-/- Mouse Model of Preeclampsia/Fetal Growth Restriction
Authors: Stanley, J. L.
Sulek, K.
Andersson, I. J.
Davidge, S. T.
Kenny, L. C.
Sibley, C. P.
Mandal, R.
Wishart, D. S.
Broadhurst, D. I.
Baker, Philip Newton
First Published: 15-Dec-2015
Publisher: Nature Publishing Group: Open Access Journals
Citation: Scientific Reports, 2015, 5, 18241
Abstract: Preeclampsia (PE) and fetal growth restriction (FGR) are serious complications of pregnancy, associated with greatly increased risk of maternal and perinatal morbidity and mortality. These complications are difficult to diagnose and no curative treatments are available. We hypothesized that the metabolomic signature of two models of disease, catechol-O-methyl transferase (COMT(-/-)) and endothelial nitric oxide synthase (Nos3(-/-)) knockout mice, would be significantly different from control C57BL/6J mice. Further, we hypothesised that any differences in COMT(-/-) mice would be resolved following treatment with Sildenafil, a treatment which rescues fetal growth. Targeted, quantitative comparisons of serum metabolic profiles of pregnant Nos3(-/-), COMT(-/-) and C57BL/6J mice were made using a kit from BIOCRATES. Significant differences in 4 metabolites were observed between Nos3(-/-) and C57BL/6J mice (p < 0.05) and in 18 metabolites between C57BL/6J and COMT(-/-) mice (p < 0.05). Following treatment with Sildenafil, only 5 of the 18 previously identified differences in metabolites (p < 0.05) remained in COMT(-/-) mice. Metabolomic profiling of mouse models is possible, producing signatures that are clearly different from control animals. A potential new treatment, Sildenafil, is able to normalize the aberrant metabolomic profile in COMT(-/-) mice; as this treatment moves into clinical trials, this information may assist in assessing possible mechanisms of action.
DOI Link: 10.1038/srep18241
eISSN: 2045-2322
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015, the authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Appears in Collections:Published Articles, College of Medicine, Biological Sciences and Psychology

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