Glucocorticoid exposure in early placentation induces preeclampsia in rats via interfering trophoblast development

Zhang, Dongxin; Liu, Haojing; Zeng, Jing; Miao, Xili; Huang, Wei; Chen, Hongxiang; Huang, Yu; Li, Yongsheng; Ye, Duyun

doi:10.1016/j.ygcen.2015.09.019

Cited by 34 publications

(32 citation statements)

References 40 publications

(61 reference statements)

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“…Dexamethasone administered during early placentation inhibits proliferation, migration, and invasion of trophoblasts, induces placental oxidative damage, and manifests as reduced placental and fetal size [24]. Maternal administration of glucocorticoids reduces placental weight and is associated with reduced expression of proliferative markers and increased expression of apoptotic factors [25, 26].…”

Section: Glucocorticoids Regulate the Function Of Organs In The Repromentioning

confidence: 99%

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Whirledge

Cidlowski

2017

Trends in Endocrinology & Metabolism

127

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Glucocorticoids are steroid hormones that regulate diverse cellular functions and are essential to facilitate normal physiology. Yet, stress-induced levels of glucocorticoids result in several pathologies including profound reproductive dysfunction. Compelling new evidence indicates glucocorticoids are crucial to the establishment and maintenance of reproductive function. The fertility promoting or inhibiting activity of glucocorticoids depends on timing, dose, and glucocorticoid-responsiveness within a given tissue, which is mediated by the glucocorticoid receptor. The glucocorticoid receptor gene and protein are subject to cellular processing, contributing to signaling diversity and providing a mechanism by which both physiological and stress-induced levels of glucocorticoids function in a cell-specific function. Understanding how glucocorticoids regulate fertility and infertility may lead to novel approaches to the regulation of reproductive function.

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Section: Glucocorticoids Regulate the Function Of Organs In The Repromentioning

confidence: 99%

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Whirledge

Cidlowski

2017

Trends in Endocrinology & Metabolism

127

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“…45 It has now become apparent that hypoxia and HIF-1a activation have the potential of modulating the activity of major EMT-triggering pathways by either regulating the expression levels of EMT inducers and their receptors, by affecting the expression levels of pathway associated signaling molecules and downstream effectors, or by a signal enhancing functional interaction with EMT-associated nuclear factors. 46 In this review, we have specifically focused on the transcription factors that are directly involved in the regulation of EMT signaling therefore we have not discussed hypoxia and HIF-1a in the trophoblast differentiation.…”

Section: Transcriptional Regulation Of Emtmentioning

confidence: 99%

Epithelial-mesenchymal transition during extravillous trophoblast differentiation

Davies

Pollheimer

Yong

et al. 2016

Cell Adhesion & Migration

200

134

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A successful pregnancy depends on the intricate and timely interactions of maternal and fetal cells. Placental extravillous cytotrophoblast invasion involves a cellular transition from an epithelial to mesenchymal phenotype. Villous cytotrophoblasts undergo a partial epithelial to mesenchymal transition (EMT) when differentiating into extravillous cytotrophoblasts and gain the capacity to migrate and invade. This review summarizes our current knowledge regarding known regulators of EMT in the human placenta, including the inducers of EMT, upstream transcription factors that control EMT and the downstream effectors, cell adhesion molecules and their differential expression and functions in pregnancy pathologies, preeclampsia (PE) and fetal growth restriction (FGR). The review also describes the research strategies that were used for the identification of the functional role of EMT targets in vitro. A better understanding of molecular pathways driven by placental EMT and further elucidation of signaling pathways underlying the developmental programs may offer novel strategies of targeted therapy for improving feto-placental growth in placental pathologies including PE and FGR.

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“…4,6 Glucocorticoids regulate gene expression by binding the glucocorticoid receptor (GR) and affecting gene transcription. 7 Placental trophoblast cells express high levels of the GR 8,9 and are responsive to the stress hormone, cortisol.…”

Section: Introductionmentioning

confidence: 99%

Cortisol inhibits CSF2 and CSF3 via DNA methylation and inhibits invasion in first‐trimester trophoblast cells

Smith

Witte

McGee

et al. 2017

American J Rep Immunol

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Problem Heightened maternal stress affects trophoblast function and increases risk for adverse pregnancy outcomes. Methods of Study Studies were performed using the first-trimester trophoblast cell line, Sw.71. Cytokines were quantified using qPCR and ELISA. Epigenetic regulation of cytokines was characterized by inhibiting histone deacetylation (1 μmol/L suberoylanilide hydroxamic acid [SAHA]) or methylation (5 μmol/L 5-azacytidine), or with chromatin immunoprecipitation (ChIP) with a pan-acetyl histone-3 antibody. Invasion assays used Matrigel chambers. Results Cortisol inhibited expression of CSF2 (GM-CSF) and CSF3 (G-CSF) in trophoblast cells. Cortisol-associated inhibition was dependent on DNA methylation and was not affected by acetylation. There was also a modest decrease in trophoblast invasion, not dependent on loss of CSFs. Conclusion In first-trimester trophoblast cells, the physiological glucocorticoid, cortisol, inhibited two cytokines with roles in placental development and decreased trophoblast invasion. Cortisol-associated changes in trophoblast function could increase the risk for immune-mediated abortion or other adverse pregnancy outcomes.

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Glucocorticoid exposure in early placentation induces preeclampsia in rats via interfering trophoblast development

Cited by 34 publications

References 40 publications

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Epithelial-mesenchymal transition during extravillous trophoblast differentiation

Cortisol inhibits CSF2 and CSF3 via DNA methylation and inhibits invasion in first‐trimester trophoblast cells

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