Placental membrane aging and HMGB1 signaling associated with human parturition

• Published in: Aging (Albany, NY.) Vol. 8; no. 2; pp. 216 - 230
• Main Authors: Menon, Ramkumar, Behnia, Faranak, Polettini, Jossimara, Saade, George R, Campisi, Judith, Velarde, Michael
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 01.02.2016
• Subjects: Blotting, Western; Cells, Cultured; Cellular Senescence - physiology; Enzyme-Linked Immunosorbent Assay; Female; HMGB1 Protein - metabolism; Humans; Immunohistochemistry; Labor, Obstetric - physiology; Parturition - physiology; Placenta - metabolism; Pregnancy; Research Paper; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; preterm birth; chorion; fetal membranes; inflammation; pregnancy; MAPK; SASP; DAMPs; amnion
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.100891

Aging is associated with the onset of several diseases in various organ systems; however, different tissues may age differently, rendering some of them dysfunctional sooner than others. Placental membranes (fetal amniochorionic membranes) protect the fetus throughout pregnancy, but their longevity is limited to the duration of pregnancy. The age-associated dysfunction of these membranes is postulated to trigger parturition. Here, we investigated whether cellular senescence-the loss of cell division potential as a consequence of stress-is involved in placental membrane function at term. We show telomere reduction, p38 MAPK activation, increase in p21 expression, loss of lamin B1 loss, increase in SA-β-galactosidase , and senescence-associated secretory phenotype (SASP) gene expression in placental membranes after labor and delivery (term labor [TL]) compared to membranes prior to labor at term (term, not-in-labor [TNIL]). Exposing TNIL placental membranes to cigarette smoke extract, an oxidative stress inducer, also induced markers of cellular senescence similar to those in TL placental membranes. Bioinformatics analysis of differentially expressed SASP genes revealed HMGB1 signaling among the top pathways involved in labor. Further, we show that recombinant HMGB1 upregulates the expression of genes associated with parturition in myometrial cells. These data suggest that the natural physiologic aging of placental tissues is associated with cellular senescence and human parturition.