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In this paper, we show that the cases with preeclampsia (PE) have increased circulating <jats:italic>NR4A2<\/jats:italic> transcripts compared to those with normotensive FGR. We aimed to establish whether the dysfunctional placenta mirrors the increase in <jats:italic>NR4A2<\/jats:italic> transcripts and further, to uncover the function of placental <jats:italic>NR4A2. NR4A2<\/jats:italic> expression was detected in preterm and term placental tissue; expressed higher at term. <jats:italic>NR4A2<\/jats:italic> mRNA expression and protein were not altered in placentas from preterm FGR or PE pregnancies. Hypoxia (1% O<jats:sub>2<\/jats:sub> compared to 8% O<jats:sub>2<\/jats:sub>) significantly reduced cytotrophoblast <jats:italic>NR4A2<\/jats:italic> mRNA expression, but not placental explant <jats:italic>NR4A2<\/jats:italic> expression. Silencing cytotrophoblast <jats:italic>NR4A2<\/jats:italic> expression under hypoxia (via short interfering (si)RNAs) did not alter angiogenic Placental Growth Factor, nor anti-angiogenic <jats:italic>sFlt-1<\/jats:italic> mRNA expression or protein secretion, but increased expression of cellular antioxidant, oxidative stress, inflammatory, and growth genes. <jats:italic>NR4A2<\/jats:italic> expression was also not altered in a model of tumour necrosis factor-\u03b1-induced endothelial dysfunction, or with pravastatin treatment. Further studies are required to identify the origin of the circulating transcripts in pathological pregnancies, and investigate the function of placental <jats:italic>NR4A2.<\/jats:italic><\/jats:p>","DOI":"10.1038\/s41598-021-00192-y","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T10:04:50Z","timestamp":1634637890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["NR4A2 expression is not altered in placentas from cases of growth restriction or preeclampsia, but is reduced in hypoxic cytotrophoblast"],"prefix":"10.1038","volume":"11","author":[{"given":"Natasha","family":"de Alwis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Beard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie K.","family":"Binder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha","family":"Pritchard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tu\u2019uhevaha J.","family":"Kaitu\u2019u-Lino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan P.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Owen","family":"Stock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie M.","family":"Groom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Henry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne M.","family":"Said","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Seeho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan C.","family":"Kane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie J.","family":"Hannan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,19]]},"reference":[{"issue":"55","key":"192_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3389\/fendo.2019.00055","volume":"10","author":"A Malhotra","year":"2019","unstructured":"Malhotra, A. et al. 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