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Histologic Evidence of Oxidative Stress and Premature Senescence in Preterm Premature Rupture of the Human Fetal Membranes Recapitulatedin vitro

Authors
Journal
American Journal Of Pathology
0002-9440
Publisher
Elsevier
Volume
184
Issue
6
Identifiers
DOI: 10.1016/j.ajpath.2014.02.011
Disciplines
  • Chemistry
  • Medicine

Abstract

Abstract Preterm prelabor rupture of the membranes (pPROM) may lead to preterm births (PTBs). We investigated premature senescence of fetal membranes in pPROM and spontaneous PTB with intact membranes (< 34 weeks) and the inducibility fetal membrane senescence phenotype by oxidative stress in vitro. Immunohistochemistry was performed for p53, p21, and phospho (p)-p38MAPK as markers of senescence phenotype in pPROM, PTB, and term births. Term fetal membranes were exposed to cigarette smoke extract to induce oxidative stress. Western blots documented phospho (p)-p53 and p-p38MAPK. Transmission electron microscopy assessed cellular morphology in clinical and cigarette smoke extract-treated membranes. 80% pPROM and >60% of term cells were positive for all three senescence phenotype markers and were higher than PTB (p < 0.05). p53 staining was comparable in membranes from PTB and term whereas only < 30% and < 45% of cells were positive for p21 and p38MAPK, respectively. In vitro cigarette smoke extract exposure increased p-p38MAPK without any detectable change in p-p53. Enlargement of organelles consistent with senescence phenotype was evident in pPROM and term membranes in vivo and after cigarette smoke extract treatment in vitro but was less apparent in PTB. Histologic and biochemical resemblance of pPROM and term membranes suggests premature senescence of the membranes is a mechanistic feature in pPROM and this can be phenocopied in an in vitro model.

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