Endometrial-Peritoneal Interactions during Endometriotic Lesion Establishment

M Louise Hull, Escareno CR, Claudia Rangel Escareno, Claudia Rangel‐Escareño, Godsland JM, Jane M Godsland, Doig JR, John R Doig, Claire M Johnson, Stephen C Phillips, Phillips SC, S. K. Smith, Stephen K Smith, Simon Tavaré, Cristin G Print, D. Stephen Charnock‐Jones, D Stephen Charnock-Jones
The American journal of pathology · 2008 · vol. 173(3) , pp. 700–715 · doi:10.2353/ajpath.2008.071128 · PMID:18688027 · PMC2527068 · W2056660087
article OA: bronze CC0 ⤵ 136 in-corpus citations
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This paper investigates the interactions between endometrial cells and peritoneal cells during the initial development of endometriosis lesions.

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Abstract

The pathophysiology of endometriosis remains unclear but involves a complex interaction between ectopic endometrium and host peritoneal tissues. We hypothesized that disruption of this interaction would suppress endometriotic lesion formation. We hoped to delineate the molecular and cellular dialogue between ectopic human endometrium and peritoneal tissues in nude mice as a first step toward testing this hypothesis. Human endometrium was xenografted into nude mice, and the resulting lesions were analyzed using microarrays. A novel technique was developed that unambiguously determined whether RNA transcripts identified via microarray analyses originated from human cells (endometrium) or mouse cells (mesothelium). Four key pathways (ubiquitin/proteasome, inflammation, tissue remodeling/repair, and ras-mediated oncogenesis) were revealed, demonstrating communication between host mesothelial cells and ectopic endometrium. Morphometric analysis of nude mouse lesions confirmed that necrosis, inflammation, healing and repair, and cell proliferation occurred during xenograft development. These processes were entirely consistent with the molecular networks revealed by the microarray data. The transcripts detected in the xenografts overlapped with differentially expressed transcripts in a comparison between paired eutopic and ectopic endometria from human endometriotic patients. For the first time, components of the interaction between ectopic endometrium and peritoneal stromal tissues are revealed. Targeted disruption of this dialogue is likely to inhibit endometriotic tissue formation and may prove to be an effective therapeutic strategy for endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Peritoneum Adult Animals Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Gene Expression Humans Immunohistochemistry Mice Mice, Nude Middle Aged Oligonucleotide Array Sequence Analysis Peritoneum

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