Initiation of human parturition: Signaling from senescent fetal tissues via extracellular vesicle mediated paracrine mechanism

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

A better understanding of the underlying mechanisms by which signals from the fetus initiate human parturition is required. Our recent findings support the core hypothesis that oxidative stress (OS) and cellular senescence of the fetal membranes (amnion and chorion) trigger human parturition. Fetal membrane cell senescence at term is a natural physiological response to OS that occurs as a result of increased metabolic demands by the maturing fetus. Fetal membrane senescence is affected by the activation of the p38 mitogen activated kinase-mediated pathway. Similarly, various risk factors of preterm labor and premature rupture of the membranes also cause OS-induced senescence. Data suggest that fetal cell senescence causes inflammatory senescence-associated secretory phenotype (SASP) release. Besides SASP, high mobility group box 1 and cell-free fetal telomere fragments translocate from the nucleus to the cytosol in senescent cells, where they represent damage-associated molecular pattern markers (DAMPs). In fetal membranes, both SASPs and DAMPs augment fetal cell senescence and an associated 'sterile' inflammatory reaction. In senescent cells, DAMPs are encapsulated in extracellular vesicles, specifically exosomes, which are 30-150 nm particles, and propagated to distant sites. Exosomes traffic from the fetus to the maternal side and cause laborassociated inflammatory changes in maternal uterine tissues. Thus, fetal membrane senescence and the inflammation generated from this process functions as a paracrine signaling system during parturition. A better understanding of the premature activation of these signals can provide insights into the mechanisms by which fetal signals initiate preterm parturition.

Original languageEnglish (US)
Pages (from-to)199-211
Number of pages13
JournalObstetrics and Gynecology Science
Volume62
Issue number4
DOIs
StatePublished - Jul 1 2019

Keywords

  • Aging
  • Amniochorion
  • Exosomes
  • Fetal membranes
  • Preterm birth

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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