title: Altered decorin and Smad expression in human fetal membranes in PPROM.
abstract: Humans with Ehlers-Danlos syndrome, a subtype of which is caused by abnormal decorin expression, are at increased risk of preterm birth due to preterm premature rupture of fetal membranes (PPROM). In the mouse model, the absence of decorin leads to fetal membrane abnormalities, preterm birth, and dysregulation of decorin's downstream pathway components, including the transcription factor p-Smad-2. However, the role of decorin and p-Smad-2 in idiopathic human PPROM is unknown. Fetal membranes from 20-25 pregnancies per group were obtained as a cross-sectional sample of births at one institution between January 2010 and December 2012. The groups were term, preterm without PPROM, and preterm with PPROM. Immunohistochemical analysis of fetal membranes was performed for decorin and p-Smad-2 using localization and quantification assessment. Decorin expression is developmentally regulated in fetal membranes and is decreased in preterm birth with PPROM compared to preterm birth without PPROM. In preterm with PPROM samples, the presence of infection is associated with significant decorin downregulation compared to preterm with PPROM samples without infection. The preterm with PPROM group exhibited decreased p-Smad-2 staining compared to both the term controls and the preterm-without-PPROM group. Our findings suggest that dysregulation of decorin and its downstream pathway component p-Smad-2 occurs in fetal membranes during the second trimester in pathological pregnancies, thus supporting a role for decorin and p-Smad-2 in the pathophysiology of fetal membranes and adverse pregnancy outcomes. These findings may lead to the discovery of new targets for the diagnosis and treatment of PPROM.
authors.affiliation: Department of Pediatrics, Women and Infants' Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Casie E
authors.initials: CE
authors.lastname: Horgan
authors.affiliation: Department of Pediatrics, Women and Infants' Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, Providence, Rhode Island Brown University, Providence, Rhode Island.
authors.forename: Hailey
authors.initials: H
authors.lastname: Roumimper
authors.affiliation: Department of Pediatrics, Women and Infants' Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Richard
authors.initials: R
authors.lastname: Tucker
authors.affiliation: Department of Pediatrics, Women and Infants' Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, Providence, Rhode Island blechner@wihri.org.
authors.forename: Beatrice E
authors.initials: BE
authors.lastname: Lechner
mesh_terms: D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D058575:Decorin / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D005865:Gestational Age; D006801:Humans; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology; D047928:Premature Birth / Q000378:metabolism / Q000473:pathology; D051899:Smad2 Protein / Q000378:metabolism*; D047929:Term Birth / Q000378:metabolism
chemical_list: C546878:DCN protein, human; D058575:Decorin; D010750:Phosphoproteins; C497782:SMAD2 protein, human; D051899:Smad2 Protein
keywords: PPROM; Smad; decorin; fetal membranes; preterm birth