The role of epithelial to mesenchymal transition in human amniotic membrane rupture

Carla Janzen, Suvajit Sen, Margarida Y Y Lei, Marina Gagliardi De Assumpcao, John Challis, Gautam Chaudhuri

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Abstract

Context: Biochemical weakening of the amnion is a major factor preceding preterm premature rupture of membranes (PPROMs), leading to preterm birth. Activation of matrix metalloproteinases (MMPs) is known to play a key role in collagen degradation of the amnion; however, epithelial to mesenchymal transition (EMT) that is also induced byMMPactivation has not been investigated as a mechanism for amnion weakening. Objective: To measure amniotic EMT associated with vaginal delivery (VD) compared with unlabored cesarean sections (CSs), and to assess changes in amniotic mechanical strength with pharmacologic inhibitors and inducers of EMT, thus testing the hypothesis that EMT is a key biochemical event that promotes amniotic rupture. Findings: (1)Amnions taken fromVDcontained a significantly increased number ofmesenchymal cells relative to epithelial cells compared with unlabored CS by fluorescence-activated cell sorting analysis (60% vs 10%); (2) tumor necrosis factor (TNF)-α stimulation of amniotic epithelial cells increased expression of themesenchymal marker vimentin after 2 days; (3) EMT inhibitor, etodolac, significantly increased the time and mechanical pressure required to rupture the amnion; and (4) TNF-α and another pharmacologic EMT inducer, ethacridine, decreased the time and mechanical pressure required for amnion rupture, further confirming that themesenchymal phenotype significantly weakens the amnion. Conclusions: This work demonstrated amniotic cell EMT was associated with labor and EMT decreased the tensile strength of the amnion. These findings suggest a role for EMT in the pathophysiology of PPROM and may provide a basis for development of therapies to prevent preterm labor.

Original languageEnglish
Pages (from-to)1261-1269
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume102
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017

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Janzen, C., Sen, S., Lei, M. Y. Y., De Assumpcao, M. G., Challis, J., & Chaudhuri, G. (2017). The role of epithelial to mesenchymal transition in human amniotic membrane rupture. Journal of Clinical Endocrinology and Metabolism, 102(4), 1261-1269. https://doi.org/10.1210/jc.2016-3150