Dataset Information

An additive interaction between the NFkappaB and estrogen receptor signalling pathways in human endometrial epithelial cells.

ABSTRACT:

Background

Human embryo implantation is regulated by estradiol (E2), progesterone and locally produced mediators including interleukin-1beta (IL-1beta). Interactions between the estrogen receptor (ER) and NF kappa B (NFkappaB) signalling pathways have been reported in other systems but have not been detailed in human endometrium.

Methods and results

Real-time PCR showed that mRNA for the p65 and p105 NFkappaB subunits is maximally expressed in endometrium from the putative implantation window. Both subunits are localized in the endometrial epithelium throughout the menstrual cycle. Reporter assays for estrogen response element (ERE) activity were used to examine functional interactions between ER and NFkappaB in telomerase immortalized endometrial epithelial cells (TERT-EEC). E2 and IL-1beta treatment of TERT-EECs enhances ERE activity by a NFkappaB and ER dependent mechanism; this effect could be mediated by ERalpha or ERbeta. E2 and IL-1beta also positively interact to increase endogenous gene expression of prostaglandin E synthase and c-myc. This is a gene-dependent action as there is no additive effect on cyclin D1 or progesterone receptor expression.

Conclusion

In summary, we have established that NFkappaB signalling proteins are expressed in normal endometrium and report that IL-1beta can enhance the actions of E2 in a cell line derived from healthy endometrium. This mechanism may allow IL-1beta, possibly from the developing embryo, to modulate the function of the endometrial epithelium to promote successful implantation, for example by regulating prostaglandin production. Aberrations in the interaction between the ER and NFkappaB signalling pathways may have a negative impact on implantation contributing to pathologies such as early pregnancy loss and infertility.

SUBMITTER: King AE

PROVIDER: S-EPMC2806182 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Publications

An additive interaction between the NFkappaB and estrogen receptor signalling pathways in human endometrial epithelial cells.

King A E AE Collins F F Klonisch T T Sallenave J-M JM Critchley H O D HO Saunders P T K PT

Human reproduction (Oxford, England) 20091202 2

<h4>Background</h4>Human embryo implantation is regulated by estradiol (E2), progesterone and locally produced mediators including interleukin-1beta (IL-1beta). Interactions between the estrogen receptor (ER) and NF kappa B (NFkappaB) signalling pathways have been reported in other systems but have not been detailed in human endometrium.<h4>Methods and results</h4>Real-time PCR showed that mRNA for the p65 and p105 NFkappaB subunits is maximally expressed in endometrium from the putative implant ...[more]

PMID: 19955102

Similar Datasets

Project description:CONTEXT:Poor uterine receptivity is one major factor leading to pregnancy loss and infertility. Understanding the molecular events governing successful implantation is hence critical in combating infertility. OBJECTIVE:To define Progesterone Receptor (PGR)-regulated molecular mechanisms and epithelial roles in receptivity. DESIGN:RNA-sequencing and PGR-ChIP-seq were conducted in parallel to identify PGR-regulated pathways during the Window of implantation (WOI) in endometrium of fertile women. SETTING:Endometrial biopsies from the proliferative and mid-secretory phases were analyzed. PATIENTS OR OTHER PARTICIPANTS:Participants were fertile, reproductive aged (18-37 years) women with normal cycle length, and without any history of dysmenorrhea, infertility, or irregular cycles. In total, 42 endometrial biopsies obtained from 42 women were analyzed in this study. INTERVENTIONS:There were no interventions during this study. MAIN OUTCOME MEASURES:Here we measured the alterations in gene expression and PGR occupancy in the genome during the WOI, based on the hypothesis that PGR binds uterine chromatin cycle dependently to regulate genes involved in uterine cell differentiation and function. RESULTS:653 genes were identified with regulated PGR binding and differential expression during the WOI. These were involved in regulating inflammatory response, xenobiotic metabolism, epithelial mesenchymal transition, cell death, interleukin/Signal Transducer And Activator Of Transcription (STAT) signaling, estrogen response, and Mammalian target of rapamycin complex 1 (MTORC1) response. Transcriptome of the epithelium identified 3052 differentially expressed genes, of which 658 were uniquely regulated. Transcription factors Interferon Regulatory Factor 8 (IRF8) and Myocyte Enhancer Factor 2C (MEF2C) were found to be regulated in the epithelium during the WOI at the protein level, suggesting potentially important functions that are previously unrecognized. CONCLUSION:PGR binds the genomic regions of genes regulating critical processes in uterine receptivity and function.

Dataset Information

An additive interaction between the NFkappaB and estrogen receptor signalling pathways in human endometrial epithelial cells.

Background

Methods and results

Conclusion

Publications

An additive interaction between the NFkappaB and estrogen receptor signalling pathways in human endometrial epithelial cells.

Similar Datasets

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