TY - JOUR
T1 - Healing of Preterm Ruptured Fetal Membranes
AU - Mogami, Haruta
AU - Hari Kishore, Annavarapu
AU - Akgul, Yucel
AU - Word, R. Ann
N1 - Funding Information:
We thank Mr. Jesus’ Acevedo and Ms. Haolin Shi for pregnant mice preparation, the physicians and staff of Parkland Memorial Hospital, and Ms. Sylvia Wright for valuable assistance in tissue procurement. We also thank the shared resource cores in Microscopic Imaging, Molecular Pathology (Mr. John Shelton), Electron Microscopy (Dr. Anza Darehshouri and Ms. Phoebe Doss) at UTSWMC for technical support. This work was supported by March of Dimes Foundation Premature Research Initiation grants #21-FY13–35 and #21-FY15-138. The Tissue Acquisition Core supported by NIH P01HD087150 is gratefully acknowledged.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Preterm premature rupture of membrane (pPROM) is associated with 30-40% of preterm births. Infection is considered a leading cause of pPROM due to increased levels of proinflammatory cytokines in amniotic fluid. Only 30%, however, are positive for microbial organisms by amniotic fluid culture. Interestingly, in some pregnancies complicated by preterm premature rupture of membranes (pPROM), membranes heal spontaneously and pregnancy continues until term. Here, we investigated mechanisms of amnion healing. Using a preclinical mouse model, we found that small ruptures of the fetal membrane closed within 72 h whereas healing of large ruptures was only 40%. Small rupture induced transient upregulation of cytokines whereas large ruptures elicited sustained upregulation of proinflammatory cytokines in the fetal membranes. Fetal macrophages from amniotic fluid were recruited to the wounded amnion where macrophage adhesion molecules were highly expressed. Recruited macrophages released limited and well-localized amounts of IL-1β and TNF which facilitated epithelial-mesenchymal transition (EMT) and epithelial cell migration. Arg1 + macrophages dominated within 24 h. Migration and healing of the amnion mesenchymal compartment, however, remained compromised. These findings provide novel insights regarding unique healing mechanisms of amnion.
AB - Preterm premature rupture of membrane (pPROM) is associated with 30-40% of preterm births. Infection is considered a leading cause of pPROM due to increased levels of proinflammatory cytokines in amniotic fluid. Only 30%, however, are positive for microbial organisms by amniotic fluid culture. Interestingly, in some pregnancies complicated by preterm premature rupture of membranes (pPROM), membranes heal spontaneously and pregnancy continues until term. Here, we investigated mechanisms of amnion healing. Using a preclinical mouse model, we found that small ruptures of the fetal membrane closed within 72 h whereas healing of large ruptures was only 40%. Small rupture induced transient upregulation of cytokines whereas large ruptures elicited sustained upregulation of proinflammatory cytokines in the fetal membranes. Fetal macrophages from amniotic fluid were recruited to the wounded amnion where macrophage adhesion molecules were highly expressed. Recruited macrophages released limited and well-localized amounts of IL-1β and TNF which facilitated epithelial-mesenchymal transition (EMT) and epithelial cell migration. Arg1 + macrophages dominated within 24 h. Migration and healing of the amnion mesenchymal compartment, however, remained compromised. These findings provide novel insights regarding unique healing mechanisms of amnion.
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U2 - 10.1038/s41598-017-13296-1
DO - 10.1038/s41598-017-13296-1
M3 - Article
C2 - 29030612
AN - SCOPUS:85031689734
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 13139
ER -