Oral Presentation Australasia Extracellular Vesicles Conference 2017

Feto-Placental Exosomes in Human Parturition: Characterization, trafficking, and functional role (#16)

Ramkumar Menon 1 , Carlos Salomon 2
  1. Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas, USA
  2. Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Faculty of Health Sciences, University of Queensland, Brisbane, QLD, Australia

Conventional theories of human parturition initiation signaling are primarily linked to feto-maternal endocrine and immune changes in the intrauterine cavity, correlating with fetal growth and development. Homeostatic imbalances produced by these changes lead to an inflammatory overload that disrupts the maintenance of pregnancy, resulting in labor-related changes resulting in delivery of the fetus (parturition). Nonetheless, the signature of these signals and their precise mechanisms in initiating parturition are still unclear. Understanding these mechanisms are important for prevention of preterm birth (birth before 37 weeks of gestation), a major complication of pregnancy. We propose a novel paracrine signaling mechanism that can initiate human parturition mediated by fetal tissue senescence induced by oxidative stress (OS). Senescence of feto-placental tissues coincides with fetal growth and maturation and signals completion of in utero life and readiness for delivery. Senescence generates sterile inflammation within the maternal-fetal interface and exosomes released by senescent cells cargo these inflammatory markers – specifically senescence associate secretory phenotype (SASP) and damage associated molecular pattern markers (DAMPs). SASP and DAMPs are capable of enhancing inflammatory load in the uterine tissues to induce contraction (labor) at term.  Our studies using pregnant mice models have shown that fetal exosomes can be propagated to the maternal side of the uterus that can potentially enhance maternal inflammatory load. To support this concept, our experiments have shown that senescent fetal cell derived exosomes cause functional changes in the maternal uterine smooth muscle cells (myometrium) transitioning them from a quiescent to active status with gene expressions associated with contractions (labor). Thus human parturition involve a signaling mechanism through exosomes from senescent fetal cells that are proxy for fetal maturity in utero. A better understanding of these paracrine signalers and their function at term parturition is expected to help us to examine premature activation of fetal tissue senescence in response to risk exposures, untimely SASP and DAMPs loaded exosome release and their functional role in causing preterm birth.