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Although trophoblast turnover and function is altered in these conditions, their underlying aetiologies and pathophysiology remains unclear, which hampers development of therapeutic interventions. Here we review evidence that supports a role for estrogen related receptor-gamma (ESRRG) in the development of placental dysfunction in FGR and preeclampsia. This relationship deserves particular consideration because ESRRG is highly expressed in normal placenta, is reduced in FGR and preeclampsia and its expression is altered by hypoxia, which is thought to result from deficient placentation seen in FGR and preeclampsia. Several studies have also found microRNA (miRNA) or other potential upstream regulators of ESRRG negatively influence trophoblast function which could contribute to placental dysfunction seen in FGR and preeclampsia. Interestingly, miRNAs regulate ESRRG expression in human trophoblast. Thus, if ESRRG is pivotally associated with the abnormal trophoblast turnover and function it may be targeted by microRNAs or other possible upstream regulators in the placenta. This review explores altered expression of ESRRG and upstream regulation of ESRRG-mediated pathways resulting in the trophoblast turnover, placental vascularisation, and placental metabolism underlying placental dysfunctions. This demonstrates that the ESRRG pathway merits further investigation as a potential therapeutic target in FGR and preeclampsia.<\/jats:p>","DOI":"10.1530\/rep-20-0272","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T11:20:45Z","timestamp":1608722445000},"page":"R45-R60","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":21,"title":["The potential role of the\n                    <i>E<\/i>\n                    \u00a0\n                    <i>SRRG<\/i>\n                    pathway in placental dysfunction"],"prefix":"10.1093","volume":"161","author":[{"given":"Zhiyong","family":"Zou","sequence":"first","affiliation":[{"name":"Maternal and Fetal Health Research Centre , University of Manchester, St Mary\u2019s Hospital, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Forbes","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre , University of Manchester, St Mary\u2019s Hospital, Manchester, UK"},{"name":"Leeds Institute of Cardiovascular and Metabolic Medicine , Faculty of Medicine and Health, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda K","family":"Harris","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre , University of Manchester, St Mary\u2019s Hospital, 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":"Alexander E P","family":"Heazell","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre , University of Manchester, St Mary\u2019s Hospital, Manchester, UK"},{"name":"St Mary\u2019s Hospital , Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, 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