Plasma membrane receptor mediated MAPK signaling pathways are activated in human uterine cervix at parturition

Hong Wang,Ylva Vladic Stjernholm

doi:10.1186/1477-7827-5-3

Hong Wang, Ylva Vladic Stjernholm

Open Access

https://doi.org/10.1186/1477-7827-5-3

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Abstract

BackgroundCervical ripening resembles an inflammatory reaction. Estrogens induce leukocyte migration into tissue and factors promoting cervical remodeling and labor, although the mechanisms are only partially known. The aim of this study was to investigate whether plasma membrane receptor mediated pathways, known to be activated by estrogens and proinflammatory compounds, are involved in cervical ripening before labor.MethodsThe expression and distribution of mitogen activated protein kinases (MAPK), which transduce extracellular signals into intracellular responses through phosphorylation, and their intracellular targets transcription factors c-Jun and c-Fos proteins (AP-1) were analysed in cervical biopsies from term pregnant women (TP), immediately after parturition (PP), and from non-pregnant women (NP). Immunohistochemistry and RT-PCR techniques were used.ResultsCell-specific alterations in the immunostaining pattern for MAPK were observed. The expressions of activated, phosphorylated MAPK forms pERK1/2, pJNK and p38MAPK were significantly increased in cervical stroma until TP and pERK1/2 expression was significantly enhanced in PP group. c-Jun was significantly increased in cervical stroma and smooth muscle in TP as compared to NP group. c-Fos was significantly increased in stroma, squamous epithelium and glandular epithelium in PP as compared to TP group.ConclusionWe report, for the first time, cell-specific activation of pMAPKs and their targets transcription factors c-Fos and c-Jun (AP-1) proteins in human uterine cervix until term pregnancy, and immediately after parturition. These results suggest a role for MAPK activation in cervical ripening before labor.

Highlights

All three types of phosphorylated Mitogen activated protein kinases (MAPK) were positively stained in the cervix, in both cell nuclei and cytoplasm (Figure 1 and 2)
The distribution of pMAPKs by using different antibodies in the cervical connective tissue was described as following: ERK1/2 (p42/44) ERK immunostaining was observed in different compartments of the cervix by using non-phosphorylated and phosphorylated antibodies
The pERK1/2 expression was unchanged between the groups

Summary

Introduction

Estrogens induce leukocyte migration into tissue and factors promoting cervical remodeling and labor, the mechanisms are only partially known. The aim of this study was to investigate whether plasma membrane receptor mediated pathways, known to be activated by estrogens and proinflammatory compounds, are involved in cervical ripening before labor. Maternal plasma levels of estrogens increase exponentially until term pregnancy and at labor concomitant with unchanged or decreased progesterone levels [7,9,10]. Despite the high maternal plasma estradiol level present at term pregnancy, the total nuclear estrogen receptor (ER) level in the uterine cervix is markedly decreased as compared to non-pregnant, suggesting a markedly limited nuclear ER mediated biological response to estrogens at parturition [7,9]. The aim of this study was to investigate the expression and distribution of MAPKs and their intracellular target transcription factor AP-1

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