title: Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation.
abstract: Although there is significant interest in elucidating the role of placenta-derived exosomes (PdEs) during pregnancy, the exosomal profile in pregnancies complicated by gestational diabetes mellitus (GDM) remains to be established. The aim of this study was to compare the gestational-age profile of PdEs in maternal plasma of GDM with normal pregnancies and to determine the effect of exosomes on cytokine release from human umbilical vein endothelial cells. A prospective cohort of patients was sampled at three time points during pregnancy for each patient (i.e., 11-14, 22-24, and 32-36 weeks' gestation). A retrospective stratified study design was used to quantify exosomes present in maternal plasma of normal (n = 13) and GDM (n = 7) pregnancies. Gestational age and pregnancy status were identified as significant factors contributing to variation in plasma exosome concentration (ANOVA, P < 0.05). Post hoc analyses established that PdE concentration increased during gestation in both normal and GDM pregnancies; however, the increase was significantly greater in GDM (∼2.2-fold, ∼1.5-fold, and ∼1.8-fold greater at each gestational age compared with normal pregnancies). Exosomes isolated from GDM pregnancies significantly increased the release of proinflammatory cytokines from endothelial cells. Although the role of exosomes during GDM remains to be fully elucidated, exosome profiles may be of diagnostic utility for screening asymptomatic populations.
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Australia Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Ochsner Clinic Foundation, New Orleans, LA c.salomongallo@uq.edu.au.
authors.forename: Carlos
authors.initials: C
authors.lastname: Salomon
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Australia.
authors.forename: Katherin
authors.initials: K
authors.lastname: Scholz-Romero
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Australia.
authors.forename: Suchismita
authors.initials: S
authors.lastname: Sarker
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Sweeney
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Australia.
authors.forename: Miharu
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Obstetrics and Gynaecology and Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Paula
authors.initials: P
authors.lastname: Correa
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Australia Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Ochsner Clinic Foundation, New Orleans, LA.
authors.forename: Sherri
authors.initials: S
authors.lastname: Longo
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Australia.
authors.forename: Gregory
authors.initials: G
authors.lastname: Duncombe
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Australia Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Ochsner Clinic Foundation, New Orleans, LA.
authors.forename: Murray D
authors.initials: MD
authors.lastname: Mitchell
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Australia Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Ochsner Clinic Foundation, New Orleans, LA Department of Obstetrics and Gynaecology and Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Rice
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Australia Department of Obstetrics and Gynaecology and Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Illanes
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D016640:Diabetes, Gestational / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D005951:Glucose Tolerance Test; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011673:Pulsatile Flow; D012372:ROC Curve; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D018608:Ultrasonography, Doppler; D055988:Uterine Artery / Q000000981:diagnostic imaging; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; C508609:IL10 protein, human; C508594:IL2 protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor