Subeen Hong1, Yehyon Park2, Yu Mi Kim2, Ji Eun Lee3, Hyeon Ji Kim2, Kyo Hoon Park2. 1. Department of Obstetrics and Gynecology, College of Medicine, Catholic University of Korea, Seoul, Korea. 2. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. 3. Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Korea.
Abstract
PROBLEM: We aimed to identify amniotic fluid (AF) proteins associated with the subsequent rupture of membranes (ROM) occurring in the absence of active labor in women with threatened preterm labor (PTL) using an antibody microarray. METHOD OF THE STUDY: This retrospective cohort study included 183 singleton pregnant women with PTL (24-33 weeks) who underwent amniocentesis. A nested case-control study was conducted using AF samples from 20 women with subsequent ROM within 7 days of sampling (case subjects) and 20 gestational age-matched women with term delivery (TD) without ROM (control subjects), via protein-antibody microarray analysis. Seven candidate proteins of interest were validated via ELISA in the total cohort. RESULTS: Seventeen proteins displayed significant intergroup differences. ELISA validation confirmed that the levels of EN-RAGE, Fas, IL-8, IP-10, MMP-8, and MMP-9 were significantly higher, whereas IGFBP-3 levels were significantly lower in the AF of women with subsequent ROM within 7 days of sampling than in that of women with TD without ROM. Moreover, the time interval from sampling to membrane rupture was significantly correlated with the expression levels of AF proteins, except for IL-10. CONCLUSION: Using an antibody microarray, we identified various inflammatory, angiogenic, matrix-degrading, and apoptosis-related proteins in the AF that were associated with subsequent ROM occurring in the absence of active labor in women with threatened PTL. These findings provide novel insights into the molecular mechanisms underlying membrane rupture without active labor in threatened PTL.
PROBLEM: We aimed to identify amniotic fluid (AF) proteins associated with the subsequent rupture of membranes (ROM) occurring in the absence of active labor in women with threatened preterm labor (PTL) using an antibody microarray. METHOD OF THE STUDY: This retrospective cohort study included 183 singleton pregnant women with PTL (24-33 weeks) who underwent amniocentesis. A nested case-control study was conducted using AF samples from 20 women with subsequent ROM within 7 days of sampling (case subjects) and 20 gestational age-matched women with term delivery (TD) without ROM (control subjects), via protein-antibody microarray analysis. Seven candidate proteins of interest were validated via ELISA in the total cohort. RESULTS: Seventeen proteins displayed significant intergroup differences. ELISA validation confirmed that the levels of EN-RAGE, Fas, IL-8, IP-10, MMP-8, and MMP-9 were significantly higher, whereas IGFBP-3 levels were significantly lower in the AF of women with subsequent ROM within 7 days of sampling than in that of women with TD without ROM. Moreover, the time interval from sampling to membrane rupture was significantly correlated with the expression levels of AF proteins, except for IL-10. CONCLUSION: Using an antibody microarray, we identified various inflammatory, angiogenic, matrix-degrading, and apoptosis-related proteins in the AF that were associated with subsequent ROM occurring in the absence of active labor in women with threatened PTL. These findings provide novel insights into the molecular mechanisms underlying membrane rupture without active labor in threatened PTL.