Oxidative stress induces p38MAPK-dependent senescence in the feto-maternal interface cells

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Abstract

Objective: This study tested the mechanism of the oxidative stress (OS)-induced senescence pathway at the feto-maternal interface cells. Methods: Primary amnion mesenchymal cells (AMCs), chorion and decidual cells isolated from the placental membranes of women at normal term (not in labor) were exposed to OS-inducing cigarette smoke extract (CSE) for 48 h. Reactive oxygen species (ROS) was measured using 2′7′-dichlorodihydrofluorescein. Western blot analysis determined phosphorylated (P) p38MAPK and p53 expression. Senescence-associated β-Galactosidase (SA-β-Gal) and matrix metallopeptidase 9 (MMP9) histochemistry were used to measure senescence and inflammation respectively. Cotreatment of cells with the antioxidant, N-acetyl cysteine (NAC), or the p38MAPK inhibitor, SB203580 (SB), verified the activation specificity. Results: CSE increased ROS production from AMCs, chorion cells, and decidual cells (P < 0.05) compared to controls. Western blot analysis determined that CSE induced p38MAPK activation (P < 0.05) and cotreatment with NAC inhibited ROS production and p38MAPK activation (P < 0.05) in all cell types. CSE did not increase p53 phosphorylation in any of the cells; however, AMCs showed constitutive P-p53 expression. CSE increased senescence in AMCs and chorion cells compared to controls (P = 0.01 and P = 0.003, respectively); however, senescence was not observed in decidual cells. Senescence was significantly reduced following cotreatment with SB and NAC (AMCs; P = 0.01 and chorion; P = 0.009). CSE increased MMP9 in all cells that was reduced by NAC. Conclusion: OS induced p38MAPK activation and inflammation in all cell types that was associated with senescence in fetal cells but not in maternal cells.

Original languageEnglish (US)
Pages (from-to)15-23
Number of pages9
JournalPlacenta
Volume67
DOIs
StatePublished - Jul 1 2018

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Keywords

  • Amnion mesenchymal cells
  • Chorion
  • Decidua
  • Oxidative stress
  • p38MAPK
  • Senescence

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

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