Expression and localization of prostaglandin receptors and stromal factors in human cervix—Variations in pregnant and non-pregnant states

Chellakkan S Blesson,Nathalie Roos,Olof Stephansson,Britt Masironi,Lena Sahlin,Ylva Vladic Stjernholm,Susann Reinert,Gunvor Ekman-Ordeberg

doi:10.4236/ojmip.2013.34020

Abstract

Prostaglandins (PGs) mediate cervical ripening leading to parturition. PGs are used successfully to induce cervical ripening. However, the cell type specific expression of PG receptor subtypes and various stromal factors important for cervical ripening in human cervix is not known. Our objective was to investigate the expression and localization of PG receptors EP1-4 and FP and localization of stromal factors CTGF (connective tissue growth factor), furin, calgranulin B, ALOX12 (arachidonate 12-lipooxy-genase) and ALOX15 in human cervical tissue from pregnant and non-pregnant women. Cervical biopsies were obtained from non-pregnant (NP), term pregnant (TP) and post-partum (PP) women. The mRNA expression was determined with real-time PCR, protein expression and localization with immunohistochemistry. Our results show that the EP2 mRNA level was higher in the PP group as compared to TP, whereas the EP4 mRNA level was lower in the TP group as compared to NP. Concomitantly stromal EP2 and epithelial EP3 immunoreactivity was higher in the TP as compared to the NP group, while the EP4 immunostaining in glands was lower in the TP as compared to the PP group. Immunostaining of endothelial CTGF, smooth muscle furin and ALOX12, were all lower in the TP group as compared to NP, for CTGF also the PP group was lower than NP. Endothelial calgranulin B immunoreactivity was higher in the PP group than the NP group. PG receptors and stromal factors exhibit differential expression in the cervix from women in non-pregnant and pregnant states, implying their involvement in the process of cervical ripening.

Highlights

Prostaglandins (PGs) are key pro-inflammatory agents that mediate cervical ripening [1]
Body Mass Index (BMI) or birth weight did not show any differences between the term pregnant (TP) and PP groups, but gestational age was lower in the TP than in the PP group (Table 1)
This difference was expected since the TP group consists of women having planned caesarean sections at term, normally seven to ten days before the estimated date of delivery according to clinical guidelines and routine ultrasound dating in the second trimester

Summary

Introduction

Prostaglandins (PGs) are key pro-inflammatory agents that mediate cervical ripening [1]. Cervical ripening is an inflammation-like process, involving the invasion of leukocytes, which facilitates the softening, dilation and effacement of the cervix [2]. Further support for the inflammation-like model of cervical ripening is given by the elevated level of IL-8 and the rise in leukocyte count at the time of labor [2,3]. Along with the inflammation mediated remodeling process of the extracellular matrix (ECM), is crucial for normal parturition [2]. The cell type specific expression of the different PG receptors in human cervix is not known. PG receptors are G-protein coupled receptors mediating smooth muscle cell contractility and relaxation through different signaling pathways [6].

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Conclusion