Research Papers: Pathology:
RNA binding protein, tristetraprolin in a murine model of recurrent pregnancy loss
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Abstract
Kasra Khalaj1,2,*, Rayana Leal Luna2,*, Maria Eduarda Rocha de França2, Wilma Helena de Oliveira2, Christina Alves Peixoto2 and Chandrakant Tayade1
1 Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada
2 Ultrastructure Laboratory, Aggeu Magalhães Research Center of the Oswaldo Cruz Foundation in Recife - FIOCRUZ, Recife, PE, Brazil
* These authors have contributed equally to this work
Correspondence to:
Christina Alves Peixoto, email:
Chandrakant Tayade, email:
Keywords: pregnancy, inflammation, RNA, RPL, 3’ UTR, Pathology Section
Received: September 23, 2016 Accepted: September 26, 2016 Published:October 09, 2016
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-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 (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-α and IL-6 were upregulated in LPS group compared to controls. We observed increased TTP nuclear immunolocalization corresponding with higher NF-κB 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.
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PII: 12539