Oxidative stress damage-associated molecular signaling pathways differentiate spontaneous preterm birth and preterm premature rupture of the membranes

Eryn H. Dutta, Faranak Behnia, Istvan Boldogh, George Saade, Brandie D. Taylor, Marian Kacerovský, Ramkumar Menon

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Study hypothesis: In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture. study finding:We demonstrate mechanistic differences between preterm birth (PTB) and PPROM by revealing differences in fetal membrane redox status, oxidative stress-induced damage, distinct signaling pathways and senescence activation. what is known already: Oxidative stress-associated fetal membrane damage and cell cycle arrest determine adverse pregnancy outcomes, such as spontaneous PTB and PPROM. study design, samples/materials, methods: Fetalmembranes and amniotic fluid samples were collected fromwomen with PTB and PPROM. Molecular, biochemical and histologic markers were used to document differences in oxidative stress and antioxidant enzyme status,DNAdamage, secondary signaling activation by Ras-GTPase and mitogen-activated protein kinases, and activation of senescence between membranes from the two groups. main results and the role of chance: Oxidative stress was higher and antioxidant enzymes were lower in PPROMcompared with PTB. PTBmembranes had minimalDNAdamage and showed activation of Ras-GTPase and ERK/JNK signaling pathway with minimal signs of senescence.PPROMhad higher numbers of cells withDNAdamage, prosenescence stress kinase (p38MAPK)activation and signs of senescence. limitations, reasons for caution: Samples were obtained retrospectively after delivery. The markers of senescence that we tested are specific but are not sufficient to confirm senescence as the pathology in PPROM. wider implications of the findings: Oxidative stress-induced DNA damage and senescence are characteristics of fetal membranes from PPROM, compared with PTB with intact membranes. PTB and PPROM arise from distinct pathophysiologic pathways. Oxidative stress and oxidative stress-induced cellular damages are likely determinants of the mechanistic signaling pathways and phenotypic outcome. study funding and competing interests: This study is supported by developmental funds to Dr R. Menon from the Department of Obstetrics and Gynecology at The University of Texas Medical Branch at Galveston and funds to Dr M. Kacerovský from the Ministry of Health Czech Republic (UHHK, 001799906). The authors report no conflict of interest.

Original languageEnglish (US)
Article numbergav074
Pages (from-to)143-157
Number of pages15
JournalMolecular Human Reproduction
Volume22
Issue number2
DOIs
StatePublished - Aug 28 2015

Keywords

  • Aging
  • Biomarkers
  • MAPK signaling
  • Oxidative stress
  • Prematurity

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Developmental Biology
  • Genetics
  • Cell Biology
  • Embryology
  • Molecular Biology

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