PMID- 29357727 OWN - NLM STAT- MEDLINE DCOM- 20191014 LR - 20220317 IS - 1476-4954 (Electronic) IS - 1476-4954 (Linking) VI - 32 IP - 14 DP - 2019 Jul TI - Amniotic fluid HIF1alpha and exosomal HIF1alpha in cervical insufficiency patients with physical examination-indicated cerclage. PG - 2287-2294 LID - 10.1080/14767058.2018.1432037 [doi] AB - OBJECTIVE: Hypoxia inducible factor 1alpha (HIF1alpha) has been reported to activate inflammatory cascade. Recently, exosomes have been known to have pivotal roles in intercellular communication. The aim of this study was to compare the concentration of amniotic fluid (AF) HIF1alpha, exosomal HIF1alpha, and inflammatory cytokines such as interleukin 1alpha (IL1alpha), interleukin 1beta (IL1beta), interleukin 6 (IL6), and tumor necrosis factor alpha (TNFalpha) between physical examination-indicated cerclage (PEIC) and control group. We also investigated the associations between biomarkers and amniocentesis-to-delivery interval and the correlations of inflammatory cytokines, HIF1alpha, and exosomal HIF1alpha. METHODS: Case-control study was performed. Cases are defined as 16 patients who underwent PEIC and controls are 19 women who underwent amniocentesis for confirming chromosomal abnormalities. The concentration of IL1alpha, IL1beta, IL6, TNFalpha, HIF1alpha, and exosomal HIF1alpha were measured using enzyme-linked immunosorbent assay (ELISA). Exosomes were confirmed by tumor susceptibility Gene 101 (TSG 101) and transmission electron microscopy (TEM). RESULTS: The mean HIF1alpha in PEIC group was higher than control group (PEIC, 15.03 +/- 9.60-pg/mL versus control, 2.96 +/- 1.99 pg/mL; p < .01). There were significant differences in inflammatory cytokines between two groups. A significant difference in exosomal HIF1alpha was shown between two groups (PEIC, 27.97 +/- 28.61-microg/mL versus control, 12.42 +/- 8.20 microg/mL; p < .01). HIF1alpha, IL1alpha, IL6, TNFalpha, and exosomal HIF1alpha showed significantly negative association with cerclage-to-delivery interval. However, IL1beta was not associated with cerclage-to-delivery interval. HIF1alpha was positively correlated with exosomal HIF1alpha (rho = 0.93, p < .01). Both HIF1alpha and exosomal HIF1alpha were significantly associated with TNFalpha (rho = 0.94, p < .01; rho = 0.97, p < .01). Both HIF-1alpha and exosomal HIF1alpha had positive correlation with IL1alpha (rho = 0.96, p < .01; rho = 0.91, p < .01). However, IL1beta showed no correlations with HIF1alpha and exosomal HIF1alpha. A positive correlation between HIF-1alpha and IL6 was observed (rho = 0.58, p = .01.) Exosomal HIF1alpha also had correlation with IL6 (rho = 0.52, p = .03). CONCLUSIONS: This study demonstrated that amniotic fluid (AF) HIF1alpha and AF exosomal HIF1alpha were higher in physical examination-indicated cerclage (PEIC) group than control group. AF HIF1alpha and AF exosomal HIF1alpha were associated with shorter amniocentesis-to-delivery interval. More importantly, they had positive correlations with AF inflammatory cytokines such as IL1alpha, IL6, and TNFalpha. Our results may indicate that AF HIF1alpha and AF exosomes interact with AF inflammatory cytokines and contribute inflammatory cascade in complicated pregnancies. FAU - Song, Ji Eun AU - Song JE AD - a Department of Obstetrics and Gynecology , Hallym University School of Medicine , Seoul , Republic of Korea. FAU - Park, Seok Ju AU - Park SJ AD - b Ilsong Institute of Life Science , Hallym University , Anyang , Republic of Korea. FAU - Lee, Keun Young AU - Lee KY AD - a Department of Obstetrics and Gynecology , Hallym University School of Medicine , Seoul , Republic of Korea. FAU - Lee, Wang Jae AU - Lee WJ AD - c Department of Anatomy , Seoul National University College of Medicine , Seoul , Republic of Korea. LA - eng PT - Journal Article DEP - 20180215 PL - England TA - J Matern Fetal Neonatal Med JT - The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians JID - 101136916 RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adult MH - Amniocentesis/statistics & numerical data MH - Amniotic Fluid/*metabolism MH - Case-Control Studies MH - Cerclage, Cervical MH - Enzyme-Linked Immunosorbent Assay MH - Exosomes/metabolism MH - Female MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*analysis MH - Infant, Newborn MH - Interleukin-1beta/analysis MH - Interleukin-6/analysis MH - Pregnancy MH - Premature Birth MH - Retrospective Studies MH - Tumor Necrosis Factor-alpha/analysis MH - Uterine Cervical Incompetence/*metabolism/surgery OTO - NOTNLM OT - Amniotic fluid OT - exosome OT - hypoxia inducible factor 1alpha OT - interleukin 1alpha OT - interleukin 1beta OT - interleukin 6 OT - physical examination-indicated cerclage OT - tumor necrosis factor alpha EDAT- 2018/01/24 06:00 MHDA- 2019/10/15 06:00 CRDT- 2018/01/24 06:00 PHST- 2018/01/24 06:00 [pubmed] PHST- 2019/10/15 06:00 [medline] PHST- 2018/01/24 06:00 [entrez] AID - 10.1080/14767058.2018.1432037 [doi] PST - ppublish SO - J Matern Fetal Neonatal Med. 2019 Jul;32(14):2287-2294. doi: 10.1080/14767058.2018.1432037. Epub 2018 Feb 15.