{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T22:02:15Z","timestamp":1747173735699,"version":"3.40.5"},"reference-count":38,"publisher":"Cambridge University Press (CUP)","issue":"3","license":[{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"},{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["www.cambridge.org"],"crossmark-restriction":true},"short-container-title":["J Dev Orig Health Dis"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The soluble fms-like tyrosine kinase factor 1 (sFlt-1) is a major contributor to antiangiogenesis during preeclampsia. However, little is known about the effects of sFlt-1 on fetal health. In this study we aim to evaluate the effects of the sFlt-1 concentration during pregnancy on fetal liver physiology. We used adenoviral gene delivery in Sprague-Dawley dams (seven females, 10 weeks old) during mid-gestation (gestational day 8) with adenovirus overexpressing sFlt-1, and age-matched controls (six females, 10 weeks old) with empty adenoviral virus in order to quantify the sFlt-1 concentrations in pregnant dams. Dams exposed to adenoviral sFlt-1 delivery were subdivided into a low (<jats:italic>n<\/jats:italic>=4) and high sFlt-1 (<jats:italic>n<\/jats:italic>=3) group based on host response to the virus. One-way analysis of variance showed that fetuses (five per dam) exposed to high sFlt-1 concentrations <jats:italic>in utero<\/jats:italic> show fetal growth restriction (1.84\u00b10.043 g high sFlt-1 <jats:italic>v.<\/jats:italic> 2.32\u00b10.036 g control; mean (M)\u00b1<jats:sc>s.e.m.<\/jats:sc>; <jats:italic>P<\/jats:italic>&lt;0.001), without hypertension or proteinuria in the dams. In continuation, the microarray analysis of the fetal liver of the high sFlt-1 group showed significant enrichment of key genes for fatty acid metabolism and Ppara targets. In addition, using pyrosequencing, we found that the Ppara enrichment in the high sFlt-1 group is accompanied by decreased methylation of its promoter (1.89\u00b10.097 mean % methylation in high sFlt-1 <jats:italic>v.<\/jats:italic> 2.26\u00b10.095 mean % methylation in control, M\u00b1<jats:sc>s.e.m.<\/jats:sc>, <jats:italic>P<\/jats:italic>&lt;0.02). Our data show that high sFlt-1 concentrations during pregnancy have detrimental effects on the fatty acid metabolism genes and the Ppara targets in the fetal liver.<\/jats:p>","DOI":"10.1017\/s2040174418000831","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T06:04:58Z","timestamp":1554876298000},"page":"353-361","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":2,"title":["<i>In utero<\/i> sFlt-1 exposure differentially affects gene expression patterns in fetal liver"],"prefix":"10.1017","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5772-2843","authenticated-orcid":false,"given":"V.","family":"Stojanovska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. M.","family":"Holwerda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. M.","family":"van der Graaf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. N.","family":"Verkaik-Schakel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. V.","family":"Boekschoten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. M.","family":"Faas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. A.","family":"Scherjon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Pl\u00f6sch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2019,4,10]]},"reference":[{"key":"S2040174418000831_ref37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00372.2015"},{"key":"S2040174418000831_ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2008.10.006"},{"key":"S2040174418000831_ref6","first-page":"170","article-title":"The impact of maternal obesity on maternal and fetal health","volume":"1","author":"Leddy","year":"2008","journal-title":"Rev Obs Gynecol"},{"key":"S2040174418000831_ref38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.05.022"},{"key":"S2040174418000831_ref24","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.115.135780"},{"key":"S2040174418000831_ref30","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev070"},{"key":"S2040174418000831_ref12","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-006-9055-8"},{"key":"S2040174418000831_ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2012.11.014"},{"key":"S2040174418000831_ref15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17189"},{"key":"S2040174418000831_ref2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-13-26"},{"key":"S2040174418000831_ref5","doi-asserted-by":"publisher","DOI":"10.1017\/S2040174417000241"},{"key":"S2040174418000831_ref21","doi-asserted-by":"publisher","DOI":"10.1113\/JP271099"},{"key":"S2040174418000831_ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2011.12.012"},{"key":"S2040174418000831_ref8","doi-asserted-by":"publisher","DOI":"10.1017\/S2040174417000290"},{"key":"S2040174418000831_ref16","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-7-538"},{"key":"S2040174418000831_ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2013.01.042"},{"key":"S2040174418000831_ref14","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25789"},{"key":"S2040174418000831_ref29","doi-asserted-by":"publisher","DOI":"10.1042\/CS20060161"},{"key":"S2040174418000831_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.12.008"},{"key":"S2040174418000831_ref3","doi-asserted-by":"publisher","DOI":"10.1111\/j.2047-6310.2012.00146.x"},{"key":"S2040174418000831_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2009.01.044"},{"key":"S2040174418000831_ref7","first-page":"214","article-title":"Birth weight and obesity risk at first grade in a cohort of Chilean children","volume":"26","author":"Loaiza","year":"2011","journal-title":"Nutr Hosp"},{"key":"S2040174418000831_ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2004.09.001"},{"key":"S2040174418000831_ref10","first-page":"950","article-title":"Preeclampsia and fetal growth","volume":"96","author":"Odegard","year":"2000","journal-title":"Obstet Gynecol"},{"key":"S2040174418000831_ref11","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2004.036715"},{"key":"S2040174418000831_ref17","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114507894438"},{"key":"S2040174418000831_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2006.12.024"},{"key":"S2040174418000831_ref19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031884"},{"key":"S2040174418000831_ref20","doi-asserted-by":"publisher","DOI":"10.1159\/000438451"},{"key":"S2040174418000831_ref22","doi-asserted-by":"publisher","DOI":"10.1002\/uog.54"},{"key":"S2040174418000831_ref23","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0000000000000051"},{"key":"S2040174418000831_ref25","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.10.2279"},{"key":"S2040174418000831_ref26","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-978592"},{"key":"S2040174418000831_ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2005.09.010"},{"key":"S2040174418000831_ref32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088584"},{"key":"S2040174418000831_ref34","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2891-13-17"},{"key":"S2040174418000831_ref35","doi-asserted-by":"publisher","DOI":"10.3945\/an.113.003798"},{"key":"S2040174418000831_ref36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.12.7543"}],"container-title":["Journal of Developmental Origins of Health and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S2040174418000831","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T08:21:13Z","timestamp":1561710073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S2040174418000831\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,10]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["S2040174418000831"],"URL":"https:\/\/doi.org\/10.1017\/s2040174418000831","relation":{},"ISSN":["2040-1744","2040-1752"],"issn-type":[{"type":"print","value":"2040-1744"},{"type":"electronic","value":"2040-1752"}],"subject":[],"published":{"date-parts":[[2019,4,10]]},"assertion":[{"value":"\u00a9 Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019.\u00a0","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}