Dataset Information

Hypomethylation of PRDM1 is associated with recurrent pregnancy loss.

ABSTRACT: Recurrent pregnancy loss (RPL) rates have continued to rise during the last few decades, yet the underlying mechanisms remain poorly understood. An emerging area of interest is the mediation of gene expression by DNA methylation during early pregnancy. Here, genome-wide DNA methylation from placental villi was profiled in both RPL patients and controls. Subsequently, differentially expressed genes were analysed for changes in gene expression. Many significant differentially methylated regions (DMRs) were identified near genes dysregulated in RPL including PRDM1. Differentially expressed genes were enriched in immune response pathways indicating that abnormal immune regulation contributes to RPL. Integrated analysis of DNA methylome and transcriptome demonstrated that the expression level of PRDM1 is fine-tuned by DNA methylation. Specifically, hypomethylation near the transcription start site of PRDM1 can recruit other transcription factors, like FOXA1 and GATA2, leading to up-regulation of gene expression and resulting in changes to trophoblast cell apoptosis and migration. These phenotypic differences may be involved in RPL. Overall, our study provides new insights into PRDM1-dependent regulatory effects during RPL and suggests both a mechanistic link between changes in PRDM1 expression, as well as a role for PRDM1 methylation as a potential biomarker for RPL diagnosis.

SUBMITTER: Du G

PROVIDER: S-EPMC7299696 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Hypomethylation of PRDM1 is associated with recurrent pregnancy loss.

Du Guizhen G Yu Mingming M Xu Qiaoqiao Q Huang Zhenyao Z Huang Xiaomin X Han Li L Fan Yun Y Zhang Yan Y Wang Ruohan R Xu Shuyu S Han Xiumei X Fu Guangbo G Lv Shuyan S Qin Yufeng Y Wang Xinru X Lu Chuncheng C Xia Yankai Y

Journal of cellular and molecular medicine 20200429 12

Recurrent pregnancy loss (RPL) rates have continued to rise during the last few decades, yet the underlying mechanisms remain poorly understood. An emerging area of interest is the mediation of gene expression by DNA methylation during early pregnancy. Here, genome-wide DNA methylation from placental villi was profiled in both RPL patients and controls. Subsequently, differentially expressed genes were analysed for changes in gene expression. Many significant differentially methylated regions (D ...[more]

PMID: 32349189

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Project description:Study questionWhat is the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature?Summary answerThe guideline development group formulated 77 recommendations answering 18 key questions on investigations and treatments for RPL, and on how care should be organized.What is known alreadyA previous guideline for the investigation and medical treatment of recurrent miscarriage was published in 2006 and is in need of an update.Study design size durationThe guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 31 March 2017 and written in English were included. Cumulative live birth rate, live birth rate and pregnancy loss rate (or miscarriage rate) were considered the critical outcomes.Participants/materials setting methodsBased on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee.Main results and the role of chanceThe guideline provides 38 recommendations on risk factors, prevention and investigations in couples with RPL, and 39 recommendations on treatments. These include 60 evidence-based recommendations - of which 31 were formulated as strong recommendations and 29 as conditional - and 17 good practice points. The evidence supporting investigations and treatment of couples with RPL is limited and of moderate quality. Of the evidence-based recommendations, only 10 (16.3%) were supported by moderate quality evidence. The remaining recommendations were supported by low (35 recommendations: 57.4%), or very low quality evidence (16 recommendations: 26.2%). There were no recommendations based on high quality evidence. Owing to the lack of evidence-based investigations and treatments in RPL care, the guideline also clearly mentions investigations and treatments that should not be used for couples with RPL.Limitations reasons for cautionSeveral investigations and treatments are offered to couples with RPL, but most of them are not well studied. For most of these investigations and treatments, a recommendation against the intervention or treatment was formulated based on insufficient evidence. Future studies may require these recommendations to be revised.Wider implications of the findingsThe guideline provides clinicians with clear advice on best practice in RPL, based on the best evidence available. In addition, a list of research recommendations is provided to stimulate further studies in RPL. One of the most important consequences of the limited evidence is the absence of evidence for a definition of RPL.Study funding/competing interestsThe guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. J.E. reports position funding from CARE Fertility. S.L. reports position funding from SpermComet Ltd. S.M. reports research grants, consulting and speaker's fees from GSK, BMS/Pfizer, Sanquin, Aspen, Bayer and Daiichi Sankyo. S.Q. reports speaker's fees from Ferring. The other authors report no conflicts of interest.ESHRE Pages are not externally peer reviewed. This article has been approved by the Executive Committee of ESHRE.

Project description:BackgroundThe treatment for recurrent pregnancy loss (RPL) has been addressed in international guidelines. However, limited studies have investigated the risk factors associated with pregnancy and live birth outcomes in patients with RPL after treatment. The objective of this study was to offer a comprehensive assessment of the risk factors for pregnancy loss in patients with a history of RPL following therapeutic interventions.MethodsThis retrospective cohort study involved 431 women in early pregnancy with a history of RPL who experienced treatment at the Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between June 2018 and June 2020. The main outcome measures were the ongoing pregnancy ≥ 12 weeks and the live birth outcomes. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for pregnancy loss < 12 weeks and live birth outcomes.ResultsPatient's age and the prevalence of uterine malformations were significantly different between the patients with and without ongoing pregnancy ≥ 12 weeks (32.64 ± 5.08 vs. 31.54 ± 4.34, P = 0.026; 34.70% vs. 24.60%, P = 0.035). The risk of pregnancy loss < 12 weeks was significantly increased with age and those with uterine abnormalities (adjusted OR: 1.48 [95% CI: 1.05 to 2.07], P = 0.025; adjusted OR:1.78 [95% CI 1.11 to 2.79], P = 0.016). The risk of non-live birth was significantly increased in couples with parental karyotype abnormalities (adjusted OR: 0.08 [95% CI 0.01 to 0.76], P = 0.029). No statistically significant differences were found between the patients with and without ongoing pregnancy ≥ 12 weeks and live birth regarding number of miscarriages, BMI, thyroid stimulating hormone, thyroid peroxidase antibody, thyroglobulin antibody, homa insulin-resistance, parental karyotype abnormality, B lymphocyte, NK cells, antinuclear antibody, antithrombin III activity, platelet aggregation function, anticardiolipin antibody, lupus anticoagulant, homocysteine, protein C, protein S, anti-β2 glycoprotein antibody, anti-phosphatidylserine and thromboelastograms.ConclusionsIn patients with RPL after treatment, age and uterine anomalies were identified as risk factors linked to pregnancy loss < 12 weeks, while parental karyotype abnormalities were recognized as an independent risk factor affecting live birth outcomes.Clinical trial numberNot applicable.

Project description:ObjectiveOxidative stress biomarkers (OSBs) may be strongly associated with disease progression and recurrent pregnancy loss (RPL). However, the research on associations of most OSBs (e.g., 8-nitroguanine [8-NO2Gua] and 4-hydroxy-2-nonenal-mercapturic acid [HNE-MA]) with RPL is limited. Therefore, we aimed to investigate the effect of OSBs exposure on RPL risk by performing a case-control study.Material and methodsWe use our established dataset, Taiwan Recurrent Pregnancy Loss and Environmental Study (TREPLES), which included 514 Taiwanese reproductive age women (aged 20-50 years; 397 cases and 117 controls) from National Cheng Kung University Hospital. RPL is clinically defined by a history of two or more consecutive miscarriages, where a miscarriage is defined as the termination of pregnancy before 20 weeks of gestation. The urinary levels of several OSBs (e.g., 8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-NO2Gua, 8-isoprostaglandin F2α [8-isoPGF2α], and HNE-MA) and malondialdehyde (MDA) were measured using isotope dilution liquid chromatography-tandem mass spectrometry and thiobarbituric acid reactive substances, respectively.ResultsThe median levels of 8-NO2Gua (6.15 vs. 3.76 ng/mL) and HNE-MA (30.12 and 21.54 ng/mL) were significantly higher in the RPL group than in the control group. By categorizing the OSBs data into tertiles, after we adjusted for age and urine creatinine levels discovered that the RPL risk associated with 8-NO2Gua and HNE-MA levels in the third tertile were approximately 2 times higher than those in the first tertile (8-NO2Gua, adjusted OR = 3.27, 95 % CI = 1.66-6.43; HNE-MA, adjusted OR = 1.96, 95 % CI = 1.05-3.64; p < 0.05). These findings suggest that the oxidative stress biomarkers of 8-NO2Gua and HNE-MA are risk factors for RPL.ConclusionOur findings indicate that specific OSBs are associated with an increased RPL risk, suggesting that reducing OSB levels can improve RPL risk. Nevertheless, more studies on preventive medicine are required to understand the exposure sources and adverse outcome pathways of OSBs associated with RPL.

Dataset Information

Hypomethylation of PRDM1 is associated with recurrent pregnancy loss.

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Hypomethylation of PRDM1 is associated with recurrent pregnancy loss.

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