Samantha Weed1, Blair Armistead2,3, Michelle Coleman3, H Denny Liggit4, Brian Johnson4, Jesse Tsai5, Richard P Beyer5, Theodor K Bammler5, Nicole M Kretzer1, Ed Parker6, Jeroen P Vanderhoeven1, Craig J Bierle3,7, Lakshmi Rajagopal2,3,7, Kristina M Adams Waldorf1,2. 1. Department of Obstetrics and Gynecology, University of Washington, Seattle Washington, USA. 2. Department of Global Health, University of Washington, Seattle, Washington, USA. 3. Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA. 4. Department of Comparative Medicine, University of Washington, Seattle, Washington, USA. 5. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA. 6. Department of Ophthalmology, University of Washington, Seattle, Washington, USA. 7. Department of Pediatric Infectious Diseases, University of Washington, Seattle, Washington, USA.
Abstract
BACKGROUND: Infection-induced preterm birth is a major cause of neonatal mortality and morbidity and leads to preterm premature rupture of placental chorioamniotic membranes. The loss of amniotic epithelial cells and tensile strength preceding membrane rupture is poorly understood. We hypothesized that intrauterine bacterial infection induces changes in microRNA (miRNA) expression, leading to amniotic epithelial cell loss and membrane weakening. METHODS: Ten pregnant pigtail macaques received choriodecidual inoculation of either group B Streptococcus (GBS) or saline (n = 5/group). Placental chorioamniotic membranes were studied using RNA microarray and immunohistochemistry. Chorioamniotic membranes from women with preterm premature rupture of membranes (pPROM) and normal term pregnancies were studied using transmission electron microscopy. RESULTS: In our model, an experimental GBS infection was associated with changes in the miRNA profile in the chorioamniotic membranes consistent with epithelial to mesenchymal transition (EMT) with loss of epithelial (E-cadherin) and gain of mesenchymal (vimentin) markers. Similarly, loss of desmosomes (intercellular junctions) was seen in placental tissues from women with pPROM. CONCLUSIONS: We describe EMT as a novel mechanism for infection-associated chorioamniotic membrane weakening, which may be a common pathway for many etiologies of pPROM. Therapy based on anti-miRNA targeting of EMT may prevent pPROM due to perinatal infection.
BACKGROUND:Infection-induced preterm birth is a major cause of neonatal mortality and morbidity and leads to preterm premature rupture of placental chorioamniotic membranes. The loss of amniotic epithelial cells and tensile strength preceding membrane rupture is poorly understood. We hypothesized that intrauterine bacterial infection induces changes in microRNA (miRNA) expression, leading to amniotic epithelial cell loss and membrane weakening. METHODS: Ten pregnant pigtail macaques received choriodecidual inoculation of either group B Streptococcus (GBS) or saline (n = 5/group). Placental chorioamniotic membranes were studied using RNA microarray and immunohistochemistry. Chorioamniotic membranes from women with preterm premature rupture of membranes (pPROM) and normal term pregnancies were studied using transmission electron microscopy. RESULTS: In our model, an experimental GBSinfection was associated with changes in the miRNA profile in the chorioamniotic membranes consistent with epithelial to mesenchymal transition (EMT) with loss of epithelial (E-cadherin) and gain of mesenchymal (vimentin) markers. Similarly, loss of desmosomes (intercellular junctions) was seen in placental tissues from women with pPROM. CONCLUSIONS: We describe EMT as a novel mechanism for infection-associated chorioamniotic membrane weakening, which may be a common pathway for many etiologies of pPROM. Therapy based on anti-miRNA targeting of EMT may prevent pPROM due to perinatal infection.
Authors: E Sánchez-Tilló; L Fanlo; L Siles; S Montes-Moreno; A Moros; G Chiva-Blanch; R Estruch; A Martinez; D Colomer; B Győrffy; G Roué; A Postigo Journal: Cell Death Differ Date: 2013-09-06 Impact factor: 15.828
Authors: M Puthiyachirakkal; K Lemerand; D Kumar; R Moore; E Philipson; B M Mercer; J M Mansour; S Hauguel-de Mouzon; J J Moore Journal: Placenta Date: 2013-08-15 Impact factor: 3.481