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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<jats:sup>\u2212\/\u2212<\/jats:sup>) and endothelial nitric oxide synthase (Nos3<jats:sup>\u2212\/\u2212<\/jats:sup>) knockout mice, would be significantly different from control C57BL\/6J mice. Further, we hypothesised that any differences in COMT<jats:sup>\u2212\/\u2212<\/jats:sup> mice would be resolved following treatment with Sildenafil, a treatment which rescues fetal growth. Targeted, quantitative comparisons of serum metabolic profiles of pregnant Nos3<jats:sup>\u2212\/\u2212<\/jats:sup>, COMT<jats:sup>\u2212\/\u2212<\/jats:sup> and C57BL\/6J mice were made using a kit from BIOCRATES. Significant differences in 4 metabolites were observed between Nos3<jats:sup>\u2212\/\u2212<\/jats:sup> and C57BL\/6J mice (p\u2009&lt;\u20090.05) and in 18 metabolites between C57BL\/6J and COMT<jats:sup>\u2212\/\u2212<\/jats:sup> mice (p\u2009&lt;\u20090.05). Following treatment with Sildenafil, only 5 of the 18 previously identified differences in metabolites (p\u2009&lt;\u20090.05) remained in COMT<jats:sup>\u2212\/\u2212<\/jats:sup> 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<jats:sup>\u2212\/\u2212<\/jats:sup> mice; as this treatment moves into clinical trials, this information may assist in assessing possible mechanisms of action.<\/jats:p>","DOI":"10.1038\/srep18241","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T10:03:06Z","timestamp":1450173786000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Sildenafil Therapy Normalizes the Aberrant Metabolomic Profile in the Comt\u2212\/\u2212 Mouse Model of Preeclampsia\/Fetal Growth Restriction"],"prefix":"10.1038","volume":"5","author":[{"given":"Joanna L.","family":"Stanley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Sulek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene J.","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra T.","family":"Davidge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise C.","family":"Kenny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin P.","family":"Sibley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupasri","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Wishart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David I.","family":"Broadhurst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip N.","family":"Baker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,12,15]]},"reference":[{"key":"BFsrep18241_CR1","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1111\/j.1471-0528.2007.01423.x","volume":"114","author":"M Knight","year":"2007","unstructured":"Knight, M. 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