Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation

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 P...

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Published inDiabetes (New York, N.Y.) Vol. 65; no. 3; pp. 598 - 609
Main Authors Salomon, Carlos, Scholz-Romero, Katherin, Sarker, Suchismita, Sweeney, Emma, Kobayashi, Miharu, Correa, Paula, Longo, Sherri, Duncombe, Gregory, Mitchell, Murray D, Rice, Gregory E, Illanes, Sebastian E
Format Journal Article
LanguageEnglish
Published United States American Diabetes Association 01.03.2016
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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.
AbstractList 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.
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.
Author Kobayashi, Miharu
Longo, Sherri
Illanes, Sebastian E
Sarker, Suchismita
Sweeney, Emma
Duncombe, Gregory
Mitchell, Murray D
Scholz-Romero, Katherin
Rice, Gregory E
Correa, Paula
Salomon, Carlos
Author_xml – sequence: 1
  givenname: Carlos
  surname: Salomon
  fullname: Salomon, Carlos
  email: c.salomongallo@uq.edu.au
  organization: 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
– sequence: 2
  givenname: Katherin
  surname: Scholz-Romero
  fullname: Scholz-Romero, Katherin
  organization: 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
– sequence: 3
  givenname: Suchismita
  surname: Sarker
  fullname: Sarker, Suchismita
  organization: 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
– sequence: 4
  givenname: Emma
  surname: Sweeney
  fullname: Sweeney, Emma
  organization: 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
– sequence: 5
  givenname: Miharu
  surname: Kobayashi
  fullname: Kobayashi, Miharu
  organization: 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
– sequence: 6
  givenname: Paula
  surname: Correa
  fullname: Correa, Paula
  organization: Department of Obstetrics and Gynaecology and Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile
– sequence: 7
  givenname: Sherri
  surname: Longo
  fullname: Longo, Sherri
  organization: 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
– sequence: 8
  givenname: Gregory
  surname: Duncombe
  fullname: Duncombe, Gregory
  organization: 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
– sequence: 9
  givenname: Murray D
  surname: Mitchell
  fullname: Mitchell, Murray D
  organization: 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
– sequence: 10
  givenname: Gregory E
  surname: Rice
  fullname: Rice, Gregory E
  organization: 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
– sequence: 11
  givenname: Sebastian E
  surname: Illanes
  fullname: Illanes, Sebastian E
  organization: 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
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ContentType Journal Article
Copyright 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Copyright American Diabetes Association Mar 2016
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License 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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Snippet Although there is significant interest in elucidating the role of placenta-derived exosomes (PdEs) during pregnancy, the exosomal profile in pregnancies...
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StartPage 598
SubjectTerms Adolescent
Adult
Case-Control Studies
Cytokines
Cytokines - metabolism
Diabetes
Diabetes, Gestational - metabolism
Enzyme-Linked Immunosorbent Assay
Exosomes - metabolism
Female
Gestational Age
Glucose Tolerance Test
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Human Umbilical Vein Endothelial Cells - metabolism
Humans
Infant, Newborn
Inflammation
Interferon-gamma - metabolism
Interleukin-10 - metabolism
Interleukin-2 - metabolism
Interleukin-4 - metabolism
Interleukin-6 - metabolism
Interleukin-8 - metabolism
Male
Placenta - metabolism
Plasma
Pregnancy
Pregnancy Trimester, Second
Pregnancy Trimester, Third
Pulsatile Flow
ROC Curve
Tumor Necrosis Factor-alpha - metabolism
Ultrasonography, Doppler
Uterine Artery - diagnostic imaging
Young Adult
Title Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation
URI https://www.ncbi.nlm.nih.gov/pubmed/26718504
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