TY - JOUR
T1 - The role of epithelial to mesenchymal transition in human amniotic membrane rupture
AU - Janzen, Carla
AU - Sen, Suvajit
AU - Lei, Margarida Y Y
AU - De Assumpcao, Marina Gagliardi
AU - Challis, John
AU - Chaudhuri, Gautam
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85017308993&partnerID=8YFLogxK
U2 - 10.1210/jc.2016-3150
DO - 10.1210/jc.2016-3150
M3 - Article
C2 - 28388726
AN - SCOPUS:85017308993
VL - 102
SP - 1261
EP - 1269
JO - Journal of Endocrinology & Metabolism
JF - Journal of Endocrinology & Metabolism
SN - 0021-972X
IS - 4
ER -