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Oxygen Modulates the Response of First-Trimester Trophoblasts to Hyperglycemia.
MedLine Citation:
PMID:  22056361     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Pregestational diabetes retards early embryonic growth. Placental and fetal growth are closely associated, suggesting that placental growth is also impaired. During the first trimester of gestation, oxygen tension rises steeply, leading to excessive production of reactive oxygen species (ROS), which is exacerbated in diabetes and may affect placental development. We hypothesized that oxygen modifies hyperglycemic effects on ROS formation, resulting in decreased first-trimester trophoblast growth. This was tested using a first-trimester trophoblast-derived cell line (ACH-3P). Normoglycemia did not alter ACH-3P proliferation at 2.5%, 8%, and 21% oxygen. Hyperglycemic conditions for up to 3 days reduced cell number by 65% and resulted in cell cycle (G(1)- and S-phase) changes but only at 21% oxygen. Proliferation reduction could be partially restored by an inhibitor of mitogen-activated protein kinase (MAPK) ERK1/2 but not of Akt/PkB. Intracellular ROS elevation under hyperglycemia was oxygen independent, whereas mitochondrial superoxide levels were enhanced under hyperglycemia only at 21% oxygen. Intervention to modulate cytosolic and mitochondrial ROS, using ROS formation inducers and inhibitors, did not alter cell growth under hyperglycemia at 21% oxygen. The combination of hyperglycemia and high oxygen levels (21%) reduces proliferation of human first-trimester trophoblasts in a ROS-independent manner involving MAPK. This may account for reduced placental growth and, therefore, also for embryonic growth during the first-trimester pregestational diabetic pregnancies when the oxygen tension increases.
Authors:
Julia D Fröhlich; Berthold Huppertz; Peter M Abuja; Julia König; Gernot Desoye
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-2
Journal Detail:
Title:  The American journal of pathology     Volume:  -     ISSN:  1525-2191     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Affiliation:
Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria; Clinic of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.
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