{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:40:07Z","timestamp":1780666807557,"version":"3.54.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Manchester and China Scholarship Council","award":["201806380004"],"award-info":[{"award-number":["201806380004"]}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R023166\/1"],"award-info":[{"award-number":["MR\/R023166\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Fetal growth restriction (FGR) describes a fetus which has not achieved its genetic growth potential; it is closely linked to placental dysfunction and uteroplacental hypoxia. Estrogen-related receptor gamma (ESRRG) is regulated by hypoxia and is highly expressed in the placenta. We hypothesized ESRRG is a regulator of hypoxia-mediated placental dysfunction in FGR pregnancies. Placentas were collected from women delivering appropriate for gestational age (AGA; n\u2009=\u200914) or FGR (n\u2009=\u200914) infants. Placental explants (n\u2009=\u200915) from uncomplicated pregnancies were cultured for up to 4\u00a0days in 21% or 1% O2, or with 200\u00a0\u03bcM cobalt chloride (CoCl2), or treated with the ESRRG agonists DY131 under different oxygen concentrations. RT-PCR, Western blotting, and immunochemistry were used to assess mRNA and protein levels of ESRRG and its localization in placental tissue from FGR or AGA pregnancies, and in cultured placental explants. ESRRG mRNA and protein expression were significantly reduced in FGR placentas, as was mRNA expression of the downstream targets of ESRRG, hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2), and cytochrome P-450 (CYP19A1.1). Hypoxia-inducible factor 1-alpha protein localized to the nuclei of the cytotrophoblasts and stromal cells in the explants exposed to CoCl2 or 1% O2. Both hypoxia and CoCl2 treatment decreased ESRRG and its downstream genes\u2019 mRNA expression, but not ESRRG protein expression. DY131 increased the expression of ESRRG signaling pathways and prevented abnormal cell turnover induced by hypoxia. These data show that placental ESRRG is hypoxia-sensitive and altered ESRRG-mediated signaling may contribute to hypoxia-induced placental dysfunction in FGR. Furthermore, DY131 could be used as a novel therapeutic approach for the treatment of placental dysfunction.<\/jats:p>","DOI":"10.1093\/biolre\/ioac108","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T19:22:02Z","timestamp":1653074522000},"page":"846-857","source":"Crossref","is-referenced-by-count":16,"title":["Placental expression of estrogen-related receptor gamma is reduced in fetal growth restriction pregnancies and is mediated by hypoxia"],"prefix":"10.1093","volume":"107","author":[{"given":"Zhiyong","family":"Zou","sequence":"first","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester , Manchester , UK"},{"name":"St. Mary\u2019s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre , Manchester , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda K","family":"Harris","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester , Manchester , UK"},{"name":"St. Mary\u2019s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre , Manchester , UK"},{"name":"Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, University of Manchester , Manchester , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Forbes","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester , Manchester , UK"},{"name":"St. Mary\u2019s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre , Manchester , UK"},{"name":"Discovery and 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tension","volume":"92","author":"Wang","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022091511335075700_ref43","doi-asserted-by":"crossref","first-page":"22642","DOI":"10.1074\/jbc.272.36.22642","article-title":"Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes","volume":"272","author":"Salceda","year":"1997","journal-title":"J Biol Chem"},{"key":"2022091511335075700_ref44","first-page":"3696","article-title":"The expression of 11 beta-hydroxysteroid dehydrogenase type 2 is induced during trophoblast differentiation: effects of hypoxia","volume":"87","author":"Hardy","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2022091511335075700_ref45","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1113\/jphysiol.2014.272856","article-title":"Mid- to late term hypoxia in the mouse alters placental morphology, glucocorticoid regulatory pathways and nutrient transporters in a sex-specific manner","volume":"592","author":"Cuffe","year":"2014","journal-title":"J Physiol"},{"key":"2022091511335075700_ref46","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.2337\/db12-0946","article-title":"Inverse agonist of nuclear receptor ERRgamma mediates antidiabetic effect through inhibition of hepatic gluconeogenesis","volume":"62","author":"Kim","year":"2013","journal-title":"Diabetes"},{"key":"2022091511335075700_ref47","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.2967\/jnumed.115.160366","article-title":"Inverse agonist of Estrogen-related receptor gamma enhances sodium iodide symporter function through mitogen-activated protein kinase Signaling in anaplastic thyroid cancer cells","volume":"56","author":"Singh","year":"2015","journal-title":"J Nucl Med"},{"key":"2022091511335075700_ref48","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1038\/s41467-018-04244-2","article-title":"Estrogen-related receptor gamma functions as a tumor suppressor in gastric cancer","volume":"9","author":"Kang","year":"2018","journal-title":"Nat Commun"},{"key":"2022091511335075700_ref49","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0143-4004(96)90041-7","article-title":"The effect of hypoxia on term trophoblast: hormone synthesis and release","volume":"17","author":"Esterman","year":"1996","journal-title":"Placenta"},{"key":"2022091511335075700_ref50","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1369\/jhc.3A6176.2004","article-title":"The influence of oxygen and tumor necrosis factor-alpha on the cellular kinetics of term placental villous explants in culture","volume":"52","author":"Crocker","year":"2004","journal-title":"J Histochem Cytochem"},{"key":"2022091511335075700_ref51","article-title":"Estrogen-related receptor gamma agonist DY131 ameliorates lipopolysaccharide-induced acute liver injury","volume":"12","author":"Ma","year":"2021","journal-title":"Front Pharmacol"},{"key":"2022091511335075700_ref52","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.1600349","article-title":"Tumor-homing peptides as tools for targeted delivery of payloads to the placenta","volume":"2","author":"King","year":"2016","journal-title":"Sci Adv"},{"key":"2022091511335075700_ref53","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.3390\/pharmaceutics13111778","article-title":"Targeted delivery of epidermal growth factor to the human placenta to treat Fetal growth restriction","volume":"13","author":"Renshall","year":"2021","journal-title":"Pharmaceutics"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioac108\/44118806\/ioac108.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/107\/3\/846\/45798780\/ioac108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/107\/3\/846\/45798780\/ioac108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T11:38:17Z","timestamp":1663241897000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/107\/3\/846\/6588705"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,19]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,5,19]]},"published-print":{"date-parts":[[2022,9,12]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioac108","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9]]},"published":{"date-parts":[[2022,5,19]]}}}