The Role of Epithelial to Mesenchymal Transition in Human Amniotic Membrane Rupture.

The Role of Epithelial to Mesenchymal Transition in Human Amniotic Membrane Rupture.

J Clin Endocrinol Metab. 2016 Dec 19;:jc20163150

Authors: Janzen C, Sen S, Lei MY, Gagliardi de Assumpcao M, Challis J, Chaudhuri G

Abstract
CONTEXT: Biochemical weakening of the amnion is a major factor preceding preterm premature rupture of membranes (PPROM), leading to preterm birth. Activation of matrix metalloproteinases (MMPs) is known to play a key role in collagen degradation of the amnion, yet epithelial to mesenchymal transition (EMT) that is also induced by MMP activation, has not been investigated as a mechanism for amnion weakening.
OBJECTIVE: To measure amniotic EMT associated with vaginal delivery (VD) as compared to non-labored cesarean sections (CS), and 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 from VD contained a significantly increased number of mesenchymal cells relative to epithelial cells as compared to unlabored cesarean section (CS) by FACS analysis (60% vs. 10%), 2) TNFα stimulation of amniotic epithelial cells increased expression of the mesenchymal marker, vimentin after 2 days 3) EMT inhibitor, etodolac, significantly increased the time and the mechanical pressure required to rupture the amnion, and 4) TNFα and another pharmacological EMT inducer, ethacridine, decreased the time and mechanical pressure required for amnion rupture, further confirming that the mesenchymal phenotype significantly weakens the amnion.
CONCLUSION: This work demonstrated that amniotic cell EMT was associated with labor, and that 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.

PMID: 27992249 [PubMed - as supplied by publisher]

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