Association of a reduction of G-protein coupled receptor 30 expression and the pathogenesis of preeclampsia

Xu, Feng; Zhou, Liyuan; Mao, Xinhua; Tong, Chao; Chen, Xuyang; Zhao, Diqi; Baker, Philip N.; Xia, Yinyin; Zhang, Hua

doi:10.3892/mmr.2017.7341

Cited by 24 publications

(21 citation statements)

References 34 publications

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“…Other animal models of preeclampsia such as L-N G -Nitroarginine methyl ester (L-Name), induce preeclamptic symptoms through chronic nitric oxide synthase inhibition 8 . However, the dose-dependent hypertension produced by the L-Name treated animals does not model the placental signaling believed to initiate the human disease 28 . The mechanical reduction in placental blood flow in the RUPP makes it ideal for validation of our spectral photoacoustic imaging methods to detect placental ischemia.…”

Section: Discussionmentioning

confidence: 99%

Spectral photoacoustic imaging to estimate in vivo placental oxygenation during preeclampsia

Lawrence

Escott

Myers

et al. 2019

Sci Rep

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Preeclampsia is a pregnancy-related hypertensive disorder accounting for 14% of global maternal deaths annually. Preeclampsia — maternal hypertension and proteinuria — is promoted by placental ischemia resulting from reduced uteroplacental perfusion. Here, we assess longitudinal changes in placental oxygenation during preeclampsia using spectral photoacoustic imaging. Spectral photoacoustic images were acquired of the placenta of normal pregnant (NP) and preeclamptic reduced uterine perfusion pressure (RUPP) Sprague Dawley rats on gestational days (GD) 14, 16, and 18, corresponding to mid- to late gestation (n = 10 per cohort). Two days after implementation of the RUPP surgical model, placental oxygen saturation decreased 12% in comparison with NP. Proteinuria was determined from a 24-hour urine collection prior to imaging on GD18. Blood pressure measurements were obtained on GD18 after imaging. Placental hypoxia in the RUPP was confirmed with histological staining for hypoxia-inducible factor (HIF)-1α, a cellular transcription regulator which responds to local oxygen levels. Using in vivo, longitudinal imaging methods we determined that the placenta in the reduced uterine perfusion pressure rat model of preeclampsia is hypoxic, and that this hypoxia is maintained through late gestation. Future work will utilize these methods to assess the impact of novel therapeutics on placental ischemia and the progression of preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Spectral photoacoustic imaging to estimate in vivo placental oxygenation during preeclampsia

Lawrence

Escott

Myers

et al. 2019

Sci Rep

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“…For example, Yin et al observed significantly higher ERα levels within the fetal part of the placenta in severe PE compared with the control group [50]. This finding is especially interesting given the reduced placental levels of another estrogen receptor, GPR30, observed by other authors in both the chorionic villi and decidua of PE patients [51]. It has also been reported that the risk of developing severe PE is associated with polymorphisms in the ESR1 gene [52] which could affect production of the receptor itself.…”

Section: Discussionmentioning

confidence: 87%

Expression of Estrogen Receptor α by Decidual Macrophages in Preeclampsia

et al. 2021

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Preeclampsia is a gestation-associated hypertensive syndrome that threatens the life and health of the mother and the child. The condition is presumably caused by systemic failure with a strong involvement of innate immunity. In particular, it has been associated with flexible phenotypes of macrophages, which depend on the molecules circulating in the blood and tissue fluid, such as cytokines and hormones. This study aimed at a comparative evaluation of pro-inflammatory (TNFα) and anti-inflammatory (CD206, MMP9, HGF) markers, as well as the levels of estrogen receptor α, expressed by decidual macrophages in normal pregnancy and in patients with early- and late-onset preeclampsia. The tissue samples of decidua basalis were examined by immunohistochemistry and Western blotting. Isolation of decidual macrophages and their characterization were performed using cultural methods, flow cytometry and real-time PCR. Over 50% of the isolated decidual macrophages were positive for the pan-macrophage marker CD68. In the early-onset preeclampsia group, the levels of estrogen receptor α in decidua were significantly decreased. Furthermore, significantly decreased levels of HGF and CD206 were observed in both preeclampsia groups compared with the control group. The observed downregulation of estrogen receptor α, HGF and CD206 may contribute to the balance of pro- and anti-inflammatory macrophages and thereby to pathogenesis of preeclampsia.

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“…Recently, a new ER denominated GPR30, which is a G-coupled receptor, has been reported [20]. This new ER participates in the nongenomic actions of E 2 and it has been associated with the estrogen-related tumorogenesis and cardioprotection [21,22], and interestingly, deficiency of GPR30 and 2ME is related to preeclampsia occurrence [23]. Probably, 2ME induces Spon1 expression via GPR30 activation in Ishikawa cells, but this remains to be demonstrated.…”

Section: Discussionmentioning

confidence: 99%

F-Spondin Is the Signal by Which 2-Methoxyestradiol Induces Apoptosis in the Endometrial Cancer Cell Line Ishikawa

Rincón‐Rodríguez

Mena

et al. 2019

IJMS

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The metabolite 2-methoxyestradiol (2ME) is an endogenous estrogen metabolite with potential therapeutic properties in reproductive cancers. However, the molecular mechanisms by which 2ME exerts its anticancer activity are not well elucidated. The purpose of this study was to determine the molecular signals associated with the apoptotic effects of 2ME in a human endometrial cancer cell line. Ishikawa cells were treated with non-apoptotic (0.1 µM) or apoptotic concentrations (5 µM) of 2ME, and 12 hours later mRNA levels for Scd2, Snx6, and Spon1 were determined by real-time PCR. We then investigated by immunofluorescence and Western blot the expression and distribution of F-spondin, encoded by Spon1, in Ishikawa cells treated with 2ME 5 µM at 6, 12, or 24 h after treatment. The role of estrogen receptors (ER) in the effect of 2ME on the Spon1 level was also investigated. Finally, we examined whether 2ME 5 µM induces cell death in Ishikawa cells pre-incubated with a neutralizing F-spondin antibody. Non-apoptotic or apoptotic concentrations of 2ME decreased Scd2 and increased Snx6. However, Spon1 was only increased with the 2ME apoptotic concentration. F-spondin protein was also increased at 12 and 24 h after 2ME treatment, while 2ME-induced Spon1 increase was independent of ER. Neutralization of F-spondin blocked the effect of 2ME on the cell viability. These results show that F-spondin signaling is one of the components in the apoptotic effects of 2ME on Ishikawa cells and provide experimental evidence underlying the mechanism of action of this estrogen metabolite on cancer cells.

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Association of a reduction of G-protein coupled receptor 30 expression and the pathogenesis of preeclampsia

Cited by 24 publications

References 34 publications

Spectral photoacoustic imaging to estimate in vivo placental oxygenation during preeclampsia

Spectral photoacoustic imaging to estimate in vivo placental oxygenation during preeclampsia

Expression of Estrogen Receptor α by Decidual Macrophages in Preeclampsia

F-Spondin Is the Signal by Which 2-Methoxyestradiol Induces Apoptosis in the Endometrial Cancer Cell Line Ishikawa

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