Human fetal membranes at term: Dead tissue or signalers of parturition?

Abstract

Various endocrine, immune, and mechanical factors produced by feto-maternal compartments at term increase intrauterine inflammatory loads to induce labor. The role of fetal (placental) membranes (amniochorion) as providers of parturition signals has not been well investigated. Fetal membranes line the intrauterine cavity and grow with and protect the fetus. Fetal membranes exist as an entity between the mother and fetus and perform unique functions during pregnancy. Membranes undergo a telomere-dependent p38 MAPK-induced senescence and demonstrate a decline in functional and mechanical abilities at term, showing signs of aging. Fetal membrane senescence is also allied with completion of fetal maturation at term as the fetus readies for delivery, which may also indicate the end of independent life and longevity of fetal membranes as their functional role concludes. Fetal membrane senescence is accelerated at term because of oxidative stress and increased stretching. Senescent fetal membranes cells produce senescence-associated secretory phenotype (SASP-inflammation) and also release proinflammatory damage-associated molecular patterns (DAMPs), namely HMGB1 and cell-free fetal telomere fragments. In a feedback loop, SASP and DAMPs increase senescence and enhance the inflammatory load to promote labor. Membranes increase the inflammatory load to disrupt homeostatic balance to transition quiescent uterine tissues toward a labor phenotype. Therefore, along with other well-described labor-promoting signals, senescent fetal membranes may also contribute to human term parturition.

Regulation of p38 mitogen‐activated kinase‐mediated fetal membrane senescence by statins

“…11,13,14 Chorioamniotic senescence is a natural physiologic process that occurs throughout gestation and is dominant at term labor. 15,16 In vitro, we have recapitulated this finding using not-in-labor, fetal membrane-derived amnion epithelial cells. 15,16 In vitro, we have recapitulated this finding using not-in-labor, fetal membrane-derived amnion epithelial cells.…”

Amnion epithelial cell–derived exosomes induce inflammatory changes in uterine cells

“…Based on recent findings of senescence in various gestational tissues that coincide with fetal growth, and our findings in fetal membrane models showing that membrane senescence and damage are associated with parturition, we hypothesized that senescent fetal membranes generate inflammatory mediators to signal fetal readiness for parturition. 25,73,74 We propose that these signals are propagated from fetal tissues to the uterine parturition effector tissues (decidua and myometrium) via fetal cell derived exosomes.…”

Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging

“…Human aging is a lifelong process that likely begins in utero (Menon, 2016) and is characterized by a dynamic phenotype that changes over time. Continuous interactions among genetic and epigenetic makeup and environmental ( e.g.…”