Menstrual effluent induces epithelial-mesenchymal transitions in mesothelial cells

Demir, A.Y., Groothuis, P.G., Nap, A.W., Punyadeera, C., de Goeij, A.F.P.M., Evers, J.L.H., & Dunselman, G.A.J. (2004) Menstrual effluent induces epithelial-mesenchymal transitions in mesothelial cells. Human Reproduction, 19(1), pp. 21-29.

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Menstrual effluent affects mesothelial cell (MC) morphology. We evaluated whether these changes were consistent with epithelial-mesenchymal transitions (EMT).


Monolayer cultures of MC were incubated overnight in conditioned media, prepared from cells isolated form menstrual effluent, with or without kinase and ATP inhibitors. Changes in cell morphology were monitored using time-lapse video microscopy and immunohistochemistry. Effects on the expression of EMT-associated molecules were evaluated using real-time RT-PCR and/or Western blot analysis.


Incubation in conditioned media disrupted cell-cell contacts, and increased MC motility. The changes were reversible. During the changes the distribution of cytokeratins, fibrillar actin and α-tubulin changed. Sodium azide, an inhibitor of ATP production, and Genistein, a general tyrosine kinase inhibitor, antagonized these effects. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, and SU6656, an Src tyrosine kinase inhibitor, only partially antagonized the effect. The expression of Snail and vimentin was markedly up-regulated, whereas the expression of E-cadherin was decreased and cytokeratins were altered.


In MC, menstrual effluent initiates a reversible, energy-dependent transition process from an epithelial to a mesenchymal phenotype. Involvement of the (Src) tyrosine kinase signalling pathway and the changes in the expression of cytokeratins, Snail, vimentin and E-cadherin demonstrate that the morphological changes are EMT.

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25 citations in Web of Science®

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ID Code: 77808
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Additional URLs:
Keywords: E-cadherin, Endometriosis, Mesothelial cells, Snail, Vimentin, 2, 3 dihydro 2 oxo 3 (4, 5, 6, 7 tetrahydro 1h indol 2 ylmethylene) 1h indole 5 sulfonic acid dimethylamide, adenosine triphosphatase, adenosine triphosphatase inhibitor, alpha tubulin, cytokeratin, F actin, genistein, phosphatidylinositol 3 kinase inhibitor, phosphotransferase inhibitor, protein, protein kinase p60 inhibitor, protein tyrosine kinase inhibitor, sodium azide, transcription factor Snail, unclassified drug, uvomorulin, wortmannin, article, cell culture, cell interaction, cell isolation, cell motility, cell structure, controlled study, culture medium, drug antagonism, drug effect, energy, epithelium cell, female, human, immunohistochemistry, incubation time, menstruation, mesenchyme cell, mesothelium cell, microscopy, molecule, phase transition, phenotype, protein expression, real time polymerase chain reaction, signal transduction, upregulation, videorecording, Western blotting, Actins, Cadherins, Cell Communication, Cell Movement, Cells, Cultured, Culture Media, Conditioned, DNA-Binding Proteins, Epithelial Cells, Humans, Indoles, Keratins, Omentum, RNA, Messenger, Sulfonamides, Tissue Distribution, Transcription Factors, Tubulin, Up-Regulation, Gastropoda
DOI: 10.1093/humrep/deh042
ISSN: 0268-1161
Deposited On: 19 Oct 2014 23:41
Last Modified: 30 Jan 2015 05:20

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