Metabolic syndrome mediates inflammatory and oxidative stress responses in patients with recurrent pregnancy loss

Azizi, Ramyar; Soltani‐Zangbar, Mohammad Sadegh; Sheikhansari, Golshan; Pourmoghadam, Zahra; Mehdizadeh, Amir; Mahdipour, Mahdi; Sandoghchian, Siamak; Danaii, Shahla; Koushaein, Ladan; Kafil, Hossein Samadi; Yousefi, Mehdi

doi:10.1016/j.jri.2019.05.001

Cited by 31 publications

(19 citation statements)

References 36 publications

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“…Recurrent spontaneous abortion (RSA) refers to spontaneous abortion that occurs for more than three times continuously between the patient and the same partner (1). Other studies showed that more than 60% of the women, who have two consecutive spontaneous abortions, were more likely to have spontaneous abortion in a second pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Effect of immunotherapy on patients with unexplained recurrent spontaneous abortion

et al. 2020

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Background: At present, it is generally believed that immune factors account for 60% of unexplained recurrent spontaneous abortion (URSA). The treatments used for URSA depend on immunomodulation for their effects, and paternal immunization, intravenous immunoglobulin, and the use of growth factors such as granulocyte-colony stimulating factor (filgrastim) have been shown to have a beneficial effect on patients with a poor prognosis. However, these treatment schemes and effects remain controversial. This study aimed to evaluate the effect of immunotherapy using lymphocyte active immunotherapy (LAI) on patients with URSA, and to provide evidences for the clinical effect of this treatment. Methods:The detailed data of total 619 patients with URSA were collected and analyzed, of which 465 patients (LAI group) with immunotherapy and 154 patients (control group) without immunotherapy.Results: After 77.6% of all the patients in LAI group received the immunotherapy, the maternal blocking antibody (BA) was changed from negative to positive. The conversion rate of maternal BA was increased as the increase of active immunization (>4 times, P<0.05). The pregnancy rate of LAI Group was higher than that of the control group (P<0.05), and there were significant differences of live rate and abortion rate (P<0.05). In addition, compared with the natural pregnancy, the live rate was higher, and the abortion rate was lower in in vitro fertilization (IVF) patients after active immunization, although the difference was not significant (P>0.05).Conclusions: After lymphocyte immunotherapy, most of the patients with unexplained recurrent spontaneous abortion had the positive BA instead of negative BA. Whether the BA was converted or not, the pregnancy rate and live rate were increased, and the abortion rate was decreased after immunotherapy. Therefore, active immunotherapy could improve the pregnancy outcome of the patients with unexplained recurrent abortion.

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Section: Introductionmentioning

confidence: 99%

Effect of immunotherapy on patients with unexplained recurrent spontaneous abortion

et al. 2020

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“…Therefore, miR-146a may be involved in the FFA-oxidative stress-fatty liver axis. Azizi et al reported that miR-146a was significantly decreased under increased oxidative stress conditions (57). Therefore, FFA may inhibit the expression level of miR-146a by increasing the level of oxidative stress, but further investigation is needed.…”

Section: Discussionmentioning

confidence: 98%

miR‑146a improves hepatic lipid and glucose metabolism by targeting MED1

Bao

Wei

et al. 2019

Int J Mol Med

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Non-alcoholic fatty liver disease (NAFLd) is one of the most common chronic liver diseases worldwide. Increasing evidence has shown that microRNAs (miRNAs) play a vital role in the progression of NAFLd. The aim of the present study was to examine the expression level and roles of miR-146a in fatty liver of high-fat diet (HFd) and ob/ob mice and fatty acid-treated hepatic cells using RT-qPcR and western blot analysis. The results showed that the expression of miR-146a was significantly decreased in the livers of high-fat diet (HFd) and ob/ob mice and free fatty acid-stimulated cells by RT-qPcR. Overexpression of hepatic miR-146a improved glucose and insulin tolerance as well as lipid accumulation in the liver by promoting the oxidative metabolism of fatty acids. In addition, the overexpression of miR-146a increased the amount of mitochondria and promoted mitochondrial respiration in hepatocytes. Similarly, inhibition of miR-146a expression levels significantly reduced mitochondrial numbers in AML12 cells as well as the expression of mitochondrial respiration related genes. Additionally, MEd1 was a direct target of miR-146a and restoring MEd1 abolished the metabolic effects of miR-146a on lipid metabolism and mitochondrial function. Therefore, results of the present study identified a novel function of miR-146a in glucose and lipid metabolism in targeting MEd1, suggesting that miR-146a serves as a potential therapeutic target for metabolic syndrome disease.

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“…Of note, inflammation, hypoxia and oxidative stress has been revealed to affect trophoblast invasion [36][37][38]. Dysregulated miR-146a expression was noticed in patients with recurrent pregnancy loss, concurrent with increased inflammatory and oxidative stress responses [39], and it could attenuate oxygen-glucose deprivation/reoxygenationinduced cardiomyocyte apoptosis [40]. Therefore, it could be an interesting topic to evaluate the impact of miR-146a-5p on trophoblast cell invasion from the perspectives of inflammatory, hypoxia and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

et al. 2021

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Objective This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). Methods Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. Results Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. Conclusion miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

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Metabolic syndrome mediates inflammatory and oxidative stress responses in patients with recurrent pregnancy loss

Cited by 31 publications

References 36 publications

Effect of immunotherapy on patients with unexplained recurrent spontaneous abortion

Effect of immunotherapy on patients with unexplained recurrent spontaneous abortion

miR‑146a improves hepatic lipid and glucose metabolism by targeting MED1

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

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