PMID- 29598691
OWN - NLM
STAT- MEDLINE
DCOM- 20190916
LR  - 20200306
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Print)
IS  - 1547-3287 (Linking)
VI  - 27
IP  - 10
DP  - 2018 May 15
TI  - Intrauterine Hyperglycemia Is Associated with an Impaired Postnatal Response to 
      Oxidative Damage.
PG  - 683-691
LID - 10.1089/scd.2017.0232 [doi]
AB  - Hyperglycemia and other adverse exposures early in life that reprogram stem cells 
      may lead to long-lasting phenotypic influences over the lifetime of an 
      individual. Hyperglycemia and oxidative stress cause DNA damage when they exceed 
      the protective capabilities of the cell, in turn affecting cellular function. DNA 
      damage in response to hyperglycemia and oxidative stress was studied in human 
      umbilical cord mesenchymal stem cells (hUC-MSCs) from large-for-gestational-age 
      (LGA) infants of mothers with gestational diabetes mellitus (LGA-GDM) and control 
      subjects. We tested the response of these cells to hyperglycemia and oxidative 
      stress, measuring reactive oxygen species (ROS) levels and antioxidant enzyme 
      activities. We find that hUC-MSCs from LGA-GDM infants have increased DNA damage 
      when exposed to oxidative stress. With the addition of hyperglycemic conditions, 
      these cells have an increase in ROS and a decrease in antioxidant glutathione 
      peroxidase (GPx) activity, indicating a mechanism for the increased ROS and DNA 
      damage. This study demonstrates that a memory of in utero hyperglycemia, mediated 
      through downregulation of GPx activity, leads to an increased susceptibility to 
      oxidative stress. The alteration of GPx function in self-renewing stem cells, can 
      mediate the effect of intrauterine hyperglycemia to be propagated into adulthood 
      and contribute to disease susceptibility.
FAU - Tozour, Jessica N
AU  - Tozour JN
AD  - 1 Department of Genetics and Center for Epigenomics, Albert Einstein College of 
      Medicine , Bronx, New York.
FAU - Delahaye, Fabien
AU  - Delahaye F
AD  - 1 Department of Genetics and Center for Epigenomics, Albert Einstein College of 
      Medicine , Bronx, New York.
AD  - 2 Department of Obstetrics & Gynecology and Women's Health, Albert Einstein 
      College of Medicine , Bronx, New York.
FAU - Suzuki, Masako
AU  - Suzuki M
AD  - 1 Department of Genetics and Center for Epigenomics, Albert Einstein College of 
      Medicine , Bronx, New York.
FAU - Praiss, Aaron
AU  - Praiss A
AD  - 2 Department of Obstetrics & Gynecology and Women's Health, Albert Einstein 
      College of Medicine , Bronx, New York.
FAU - Zhao, Yongmei
AU  - Zhao Y
AD  - 2 Department of Obstetrics & Gynecology and Women's Health, Albert Einstein 
      College of Medicine , Bronx, New York.
FAU - Cai, Lingguang
AU  - Cai L
AD  - 2 Department of Obstetrics & Gynecology and Women's Health, Albert Einstein 
      College of Medicine , Bronx, New York.
FAU - Heo, Hye J
AU  - Heo HJ
AD  - 3 Department of Obstetrics and Gynecology, NYU Winthrop Hospital , Mineola, New 
      York.
FAU - Greally, John M
AU  - Greally JM
AD  - 1 Department of Genetics and Center for Epigenomics, Albert Einstein College of 
      Medicine , Bronx, New York.
AD  - 4 Department of Pediatrics (Genetics), Albert Einstein College of Medicine , 
      Bronx, New York.
FAU - Hughes, Francine
AU  - Hughes F
AD  - 5 Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, 
      NYU Langone Medical Center , New York, New York.
LA  - eng
GR  - P30 DK020541/DK/NIDDK NIH HHS/United States
GR  - T32 GM007288/GM/NIGMS NIH HHS/United States
GR  - P30 CA013330/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180426
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Antioxidants)
RN  - 0 (Reactive Oxygen Species)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Antioxidants/*metabolism
MH  - Cells, Cultured
MH  - DNA Damage/physiology
MH  - Diabetes, Gestational/metabolism/pathology
MH  - Female
MH  - Glutathione/metabolism
MH  - Humans
MH  - Hyperglycemia/metabolism/*pathology
MH  - Mesenchymal Stem Cells/metabolism/physiology
MH  - Oxidation-Reduction
MH  - Oxidative Stress/*physiology
MH  - Pregnancy
MH  - Reactive Oxygen Species/metabolism
MH  - Umbilical Cord/metabolism/pathology
MH  - Uterus/metabolism/*pathology
PMC - PMC5962324
OTO - NOTNLM
OT  - DNA damage
OT  - gestational diabetes
OT  - glutathione peroxidase
OT  - mesenchymal stem cells
OT  - oxidative stress
COIS- No competing financial interests exist.
EDAT- 2018/03/31 06:00
MHDA- 2019/09/17 06:00
PMCR- 2019/05/15
CRDT- 2018/03/31 06:00
PHST- 2018/03/31 06:00 [pubmed]
PHST- 2019/09/17 06:00 [medline]
PHST- 2018/03/31 06:00 [entrez]
PHST- 2019/05/15 00:00 [pmc-release]
AID - 10.1089/scd.2017.0232 [pii]
AID - 10.1089/scd.2017.0232 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2018 May 15;27(10):683-691. doi: 10.1089/scd.2017.0232. Epub 2018 
      Apr 26.