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-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.

Inhibition of TMUB1 blocks apoptosis and NF‐κB pathway‐mediated inflammation in recurrent spontaneous abortion

“…The administration of LPS to pregnant mice causes placental degeneration due to acute inflammation, which results in fetal loss 21,22 . Here, we found that the embryo absorption rate and abortion rate were increased in LPS‐activated mice, which confirmed the validity of LPS as a potential inducer of inflammatory response and its associated impact on the placental vasculature 23,24 . Inflammation is reported to link with the pathogenesis of the female reproductive system which causes RSA 25 .…”

“…21,22 Here, we found that the embryo absorption rate and abortion rate were increased in LPS-activated mice, which confirmed the validity of LPS as a potential inducer of inflammatory response and its associated impact on the placental vasculature. 23,24 Inflammation is reported to link with the pathogenesis of the female reproductive system which causes RSA. 25 In this study, we found that TMUB1 silencing decreased the expression of inflammatory cytokines in LPS-activated trophoblast cells, indicating the facilitating role of TMUB1 in the inflammatory response during the development of abortion.…”

RETRACTED: Elevated Tristetraprolin Impairs Trophoblast Invasion in Women with Recurrent Miscarriage by Destabilization of HOTAIR

“… 25 Moreover, Kasra Khalaj et al. 26 showed that TTP protein was downregulated in an LPS-induced mouse pregnancy loss model, and its targets TNF-α and interleukin-6 (IL-6) were upregulated.…”

Interleukin-33 modulates inflammation in endometriosis

“…Finally, sections were counterstained with haematoxylin and bluing reagent for 4 min before adding the coverslips. For CD31 and Ki67 staining, differential cell counting analyses, image analysis software was conducted using NIH ImageJ as per previously published protocol from our group 45 . Briefly, 100 cells were manually counted from three areas from three different slides in each experimental group.…”