Estrogen-related receptor γ regulates expression of 17β-hydroxysteroid dehydrogenase type 1 in fetal growth restriction

Zhu, Hui; Huang, Liwu; He, Zhiming; Zou, Zhiyong; Luo, Yang

doi:10.1016/j.placenta.2018.05.012

Cited by 13 publications

(18 citation statements)

References 39 publications

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“…Thus, the structure of the ERRs, specifically that of the LBD and DBD, is vital to the regulation of ERR signalling, including that of ESRRG. Furthermore, abnormal placental expression of ESRRG in FGR and preeclampsia suggests a potential role for ESRRG in the development or potentiation of these pregnancy complications (Luo et al 2014, Zhu et al 2018a. This review will consider how ESRRG is regulated, its effects in trophoblast and how this may contribute to the phenotypes of placental dysfunction observed in FGR and preeclampsia.…”

Section: Structure Of Errsmentioning

confidence: 99%

“…Estrogen-related receptor-gamma is a member of the ERR family of orphan nuclear receptors, which is highly expressed in the human placenta (Takeda et al 2009). Evidence suggests that ESRRG serves an important role in trophoblast differentiation, proliferation, and invasion, and may be involved in blood pressure homeostasis (Luo et al 2014, Zhu et al 2018a). In addition, deficient expression of ESRRG is linked to impaired placental mitochondrial function (Poidatz et al 2012), which could lead to inadequate energy supply and thus reduced energy expenditure within the placenta.…”

Section: Introductionmentioning

confidence: 99%

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The potential role of the E SRRG pathway in placental dysfunction

et al. 2021

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Normal placental development and function is of key importance to fetal growth. Conversely aberrations of placental structure and function are evident in pregnancy complications including fetal growth restriction (FGR) and preeclampsia. 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 (ERRγ) in the development of placental dysfunction in FGR and preeclampsia. This relationship deserves particular consideration because ERRγ 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 or other potential upstream regulators of ERRγ negatively influence trophoblast function which could contribute to placental dysfunction seen in FGR and preeclampsia. Interestingly, microRNAs regulate ERRγ expression in human trophoblast. Thus, if ERRγ 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 ERRγ and upstream regulation of ERRγ-mediated pathways resulting in the trophoblast turnover, placental vascularisation, and placental metabolism underlying placental dysfunctions. This demonstrates that the ERRγ pathway merits further investigation as a potential therapeutic target in FGR and preeclampsia.

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Section: Structure Of Errsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The potential role of the E SRRG pathway in placental dysfunction

et al. 2021

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“…Several important factors involved in the adaptive changes of uterine vascular function are dysregulated in preeclampsia and IUGR. Placental estrogen biosynthesis was impaired due to the downregulation of 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) and aromatase [29,304,305,306] in these pregnancy complications. Downregulation of BK Ca channel β1 subunit was observed in placental chorionic plate arteries in preeclampsia and uterine arteries in high-altitude pregnancy [172,307].…”

Section: Mirnas and Uteroplacental Circulation Adaptation Under Phmentioning

confidence: 99%

“…In addition, miR-22 was found to inhibit CYP19A1 expression indirectly by targeting ERα encoding gene ESR1 [319]. ERRγ a constitutively active orphan nuclear receptor, stimulated HSD17B1 expression in the placenta [306]. The expression of ESRRG could be inhibited by elevated miR-320a in preeclamptic placenta [103].…”

Section: Mirnas and Uteroplacental Circulation Adaptation Under Phmentioning

confidence: 99%

MicroRNAs in Uteroplacental Vascular Dysfunction

Zhang

2019

Cells

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Pregnancy complications of preeclampsia and intrauterine growth restriction (IUGR) are major causes of maternal and perinatal/neonatal morbidity and mortality. Although their etiologies remain elusive, it is generally accepted that they are secondary to placental insufficiency conferred by both failure in spiral artery remodeling and uteroplacental vascular malfunction. MicroRNAs (miRNAs) are small no-coding RNA molecules that regulate gene expression at the post-transcriptional level. Increasing evidence suggests that miRNAs participate in virtually all biological processes and are involved in numerous human diseases. Differentially expressed miRNAs in the placenta are typical features of both preeclampsia and IUGR. Dysregulated miRNAs target genes of various signaling pathways in uteroplacental tissues, contributing to the development of both complications. In this review, we provide an overview of how aberrant miRNA expression in preeclampsia and IUGR impacts the expression of genes involved in trophoblast invasion and uteroplacental vascular adaptation.

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“…ESRRG role in regulating placental steroidogenesis (36) has been recently proposed by an in vitro model reporting its binding to CYP19A1 promoter (35), with the consequent induction of Cytochrome p450 aromatase (37). Moreover, silencing of ESRRG in extravillous trophoblasts has been recently reported to suppress the expression of HSD17β1, another steroidogenic enzyme critical to the placental conversion of estrone to estradiol (38).…”

Section: Introductionmentioning

confidence: 99%

Placental ESRRG-CYP19A1 Expressions and Circulating 17-Beta Estradiol in IUGR Pregnancies

et al. 2019

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Introduction: Sex steroids are regulating factors for intrauterine growth. 17-β Estradiol (E2) is particularly critical to a physiological pregnancy, as increased maternal E2 was correlated to lower fetal weight at delivery. The placenta itself is a primary source of estrogens, synthetized from cholesterol precursors. Cytochrome P450 aromatase (encoded by CYP19A1 gene) is a rate-limiting enzyme for E2 biosynthesis. CYP19A1 transcription is supported by Estrogen Related-Receptor Gamma (ERRγ- ESRRG gene), which thus has an indirect role in placental steroidogenesis. Here we investigated maternal E2 levels and placental CYP19A1 and ESRRG expressions in pregnancies with IntraUterine Growth Restriction (IUGR). Methods: Singleton pregnancies were studied. E2 was measured in maternal plasma by electrochemiluminescence in 16 term controls and 11 IUGR (classified by umbilical artery doppler pulsatility index) at elective cesarean section, and also in 13 controls during pregnancy at a gestational age comparable to IUGR. CYP19A1 and ESRRG expressions were analyzed in placental tissue. Maternal/fetal characteristics, placental and molecular data were compared among study groups and tested for correlations. Results: Maternal E2 plasma concentrations were significantly decreased in IUGR compared to controls at delivery. When analyzing normal pregnancies at a gestational age similar to IUGR, E2 levels were not different to pathological cases. However, E2 levels at delivery positively correlated with placental efficiency. Placental CYP19A1 levels were significantly higher in IUGR placental tissue vs. controls, and specifically increased in female IUGR placentas. ESRRG expression was not different among groups. Discussion: We report a positive correlation between 17-β Estradiol levels and placental efficiency, that might indicate a disrupted steroidogenesis in IUGR pregnancies. Moreover, we show alterations of CYP19A1 expression in IUGR placentas, possibly indicating a compensatory effect to the adverse IUGR intrauterine environment, also depending on fetal sex. Further studies are needed to deeper investigate IUGR alterations in the complex interaction among molecules involved in placental steroidogenesis.

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Estrogen-related receptor γ regulates expression of 17β-hydroxysteroid dehydrogenase type 1 in fetal growth restriction

Cited by 13 publications

References 39 publications

The potential role of the E SRRG pathway in placental dysfunction

The potential role of the E SRRG pathway in placental dysfunction

MicroRNAs in Uteroplacental Vascular Dysfunction

Placental ESRRG-CYP19A1 Expressions and Circulating 17-Beta Estradiol in IUGR Pregnancies

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