Abstract
BackgroundCervical ripening is an inflammatory reaction. The glucocorticoid receptor (GR) mediates glucocorticoid anti-inflammatory reactions, whereas nuclear factor (NF)kappaB is a key pro-inflammatory transcription factor. Prostaglandins as well as platelet activating factor (PAF) are inflammatory mediators. Inducible nitric oxide synthase (iNOS) regulates the level of nitric oxide (NO) in response to various inflammatory stimuli. We hypothesize that a changed biological response to glucocorticoids could be a mechanism regulating the inflammatory events resulting in cervical ripening.MethodsWe monitored GR and NFkappaB, prostaglandin synthases cyclooxygenase (COX)-1 and -2, iNOS, as well as the PAF-receptor (PAF-R) in the uterine cervix from term pregnant women (with unripe cervices) before the onset of labor (TP), immediately after parturition (PP), as compared to non-pregnant (NP), using immunohistochemistry and RT-PCR.ResultsThe GR protein was detected by immunohistochemistry in the nuclei of stroma and squamous epithelium (SQ). Stromal GR staining was increased in TP as compared to the NP group and decreased again after parturition. GR staining in SQ was decreased after parturition as compared to term. NFkappaB was present in SQ and glandular epithelium (GE), stroma and vascular endothelium. Increased nuclear NFkappaB staining was observed postpartum as compared to term pregnancy in stroma and GE. Stromal immunostaining for COX-1 as well as COX-2 was increased in the TP and PP groups as compared to the NP, and GE displayed an intensely increased COX-2 immunostaining at term and postpartum. Stromal PAF-R immunostaining was highest at term, while it was greatly increased in GE postpartum.No difference in the immunostaining for iNOS was found between the groups. RT-PCR showed a predominance of GRalpha to GRbeta mRNA in cervical tissue. The COX-2 mRNA level was increased in the PP group as compared to the TP group.ConclusionsThere is a decrease in GR levels in human cervix at parturition. Concomitantly there is an increase of factors such as NFkappaB, PAF-R, COX-1 and COX-2, suggesting that they may participate in the sequence of events leading to the final cervical ripening.
Highlights
glucocorticoid receptor (GR) By immunohistochemistry the GR protein was localized to the nuclei of cervical stroma (S), squamous epithelium (SQ), glandular epithelium (GE) and vascular endothelium (Figure 1a,1b,1c,1d,1e,1f,1g,1h,1i) in samples from the NP, term pregnant (TP) and PP groups
There was a significant decrease in immunostaining of the PP group as compared to the TP group, both in stroma and SQ (Figure 2)
We conclude that GRα is the major receptor type observed in our study, GRβ could contribute to the GR protein level in the TP group
Summary
We hypothesize that a changed biological response to glucocorticoids could be a mechanism regulating the inflammatory events resulting in cervical ripening. The human uterine cervix undergoes biochemical changes resulting in softening, effacement and dilatation during pregnancy and labor. This remodeling, or ripening, is a prerequisite for parturition [1]. It is characterized by inflammatory events, such as extravasation of neutrophils and macrophages [2,3] and an increased cervical level of pro-inflammatory cytokines such as interleukin (IL)-8 [3,4]. Placental production of progesterone and adrenal synthesis of glucocorticoids [6] increase markedly during human pregnancy. Placental CRH, synthesized in abundance in the human placental syncytiotrophoblasts and trophoblasts [9], has been proposed to be a key regulator for human parturition trough interactions with adrenal steroids and estrogen [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
