Imperial College London
Alternate

Dr Kaiyu Lei

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 2137k.lei08

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Georgiou:2016:molehr/gaw037,
author = {Georgiou, EX and Lei, K and Lai, PF and Yulia, A and Herbert, BR and Castellanos, M and May, ST and Sooranna, SR and Johnson, MR},
doi = {molehr/gaw037},
journal = {Molecular Human Reproduction},
title = {The study of progesterone action in human myometrial explants.},
url = {http://dx.doi.org/10.1093/molehr/gaw037},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - STUDY HYPOTHESIS: Myometrial explants represent a superior model compared with cell culture models for the study of human myometrial progesterone (P4) signalling in parturition. STUDY FINDING: Gene expression analysis showed myometrial explants closely resemble the in vivo condition and the anti-inflammatory action of P4 is not lost with labour onset. WHAT IS KNOWN ALREADY: Circulating P4 levels decline before the onset of parturition in most animals, but not in humans. This has led to the suggestion that there is a functional withdrawal of P4 action at the myometrial level prior to labour onset. However, to date, no evidence of a loss of P4 function has been provided, with studies hampered by a lack of a physiologically relevant model. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Myometrial biopsies obtained at Caesarean section were dissected into explants after a portion was immediately snap frozen (t = 0). Microarray analysis was used to compare gene expression of t = 0 with paired (i) explants, (ii) passage 4 myometrial cell cultures or (iii) the hTERT myometrial cell line. Western blotting and chemokine/cytokine assays were used to study P4 signalling in myometrial explants. MAIN RESULTS AND THE ROLE OF CHANCE: Gene expression comparison of t = 0 to the three models demonstrated that explants more closely resemble the in vivo status. At the protein level, explants maintain both P4 receptor (PR) and glucocorticoid receptor (GR) levels versus t = 0 whereas cells only maintain GR levels. Additionally, treatment with 1 µM P4 led to a reduction in interleukin-1 (IL-1) β-driven cyclooxygenase-2 in explants but not in cells. P4 signalling in explants was PR-mediated and associated with a repression of p65 and c-Jun phosphorylation. Furthermore, the anti-inflammatory action of P4 was maintained after labour onset. LIMITATIONS/REASONS FOR CAUTION: There is evidence of basal inflammation in the myometrial explant model. WIDER IMPLICATIONS OF THE FINDINGS: Myomet
AU  - Georgiou,EX
AU  - Lei,K
AU  - Lai,PF
AU  - Yulia,A
AU  - Herbert,BR
AU  - Castellanos,M
AU  - May,ST
AU  - Sooranna,SR
AU  - Johnson,MR
DO  - molehr/gaw037
PY  - 2016///
SN  - 1460-2407
TI  - The study of progesterone action in human myometrial explants.
T2  - Molecular Human Reproduction
UR  - http://dx.doi.org/10.1093/molehr/gaw037
ER  -
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