579: Senescence associated secretory phenotype: a signal for parturition?

Abstract

Senescence of placenta and fetal membranes have been documented in term labor tissues in contrast to term not in labor. This is associated with a unique set of biomarkers called Senescence Associated Secretory Phenotype (SASP). This study documented histologic characteristics of senescence at term and the differences in amniotic fluid SASP markers at term (labor vs. non labor) to further confirm senescence associate changes associated with labor. Amniochorionic membranes (n=7) and amniotic fluids (AF) were collected from normal term deliveries; Group 1: Term labor (TL) and vaginal delivery Group 2: Term not in labor (TNIL). Term labor AF (n=29) samples were collected by transvaginal amniocentesis and TNIL (n=33) by transabdominal amniocentesis. Membranes were subjected to transmission electron microscopy (TEM) to document senescence associated changes. A Fast protein microarray technology was used to analyze 14 SASP biomarkers. Associations between SASP markers transformed to log base2 and Term L were examined using generalized linear models. Spearman correlation was used to determine among the entire cohort if any of the SASP markers were correlated. TEM showed signs of senescence in TL membranes characterized by enlarged cells and organelles, (heterochromatic nuclei, endoplasmic reticulum and mitochondria) than TNIL (Fig 1). Of the 14 markers studied, 7 markers showed significant differences. There were significant associations between GM-CSF, IL-6 and IL-8 (All p<0.01) and increased log odds of having term L. In contrast, there were significant associations between anti-cell death markers, eotaxin (p=0.056), Fas Ligand, osteoprotegerin (both p<0.0001), and adhesion molecule ICAM-1 (P<0.0001) with a decreased log odds of having term L. Senescence is associated with TL and AF SASP markers at TL are uterotonic agents.Domination of anti-cell death markers at TNIL validate that senescence generate noninfectious inflammatory markers that may signal parturition by the fetus.