Dataset Information

RNA binding protein, tristetraprolin in a murine model of recurrent pregnancy loss.

ABSTRACT: Recurrent pregnancy loss is a major reproductive pathology affecting 1-5% of pregnant women worldwide. A distinct feature of this reproductive pathology is involvement of key inflammatory cytokines and transcription factors such as tumor necrosis factor alpha (TNF-?), interleukin 6 (IL-6) and nuclear factor kappa beta (NF-?B). Special classes of RNA-binding proteins regulate the transcripts of many of these important cytokines and regulatory factors via binding to the 3' untranslated regions (UTRs) and/or poly(A) tail and destabilizing/stabilizing the transcript. The tristetraprolin (TTP/ZFP36) family have been found to be potent destabilizers of the aforementioned inflammatory and cellular response cytokines. The aim of this study was to evaluate whether tristetraprolin is expressed in the placenta and involved in modulating inflammation in mouse model of lipopolysaccharide (LPS)-induced fetal loss. In this study, Swiss-albino mice were injected with LPS at gestational day 15.5 and placental tissues were harvested 6 hours post-LPS injection. Histopathology and immunohistochemistry analyses clearly revealed cellular stress and death in LPS treated placentas compared to controls. TTP protein was downregulated, while targets TNF-? and IL-6 were upregulated in LPS group compared to controls. We observed increased TTP nuclear immunolocalization corresponding with higher NF-?B nuclear localization in trophoblasts from LPS treated placentas. Our results suggest that RNA-binding proteins such as TTP are expressed and perhaps involved in the modulation of inflammation-induced pregnancy pathologies.

SUBMITTER: Khalaj K

PROVIDER: S-EPMC5341924 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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RNA binding protein, tristetraprolin in a murine model of recurrent pregnancy loss.

Khalaj Kasra K Luna Rayana Leal RL de França Maria Eduarda Rocha ME de Oliveira Wilma Helena WH Peixoto Christina Alves CA Tayade Chandrakant C

Oncotarget 20161101 45

Recurrent pregnancy loss is a major reproductive pathology affecting 1-5% of pregnant women worldwide. A distinct feature of this reproductive pathology is involvement of key inflammatory cytokines and transcription factors such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and nuclear factor kappa beta (NF-κB). Special classes of RNA-binding proteins regulate the transcripts of many of these important cytokines and regulatory factors via binding to the 3' untranslated regions (UT ...[more]

PMID: 27732963

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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.

Dataset Information

RNA binding protein, tristetraprolin in a murine model of recurrent pregnancy loss.

Publications

RNA binding protein, tristetraprolin in a murine model of recurrent pregnancy loss.

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