Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Fröhlich, JD; Huppertz, B; Abuja, PM; König, J; Desoye, G.
Oxygen modulates the response of first-trimester trophoblasts to hyperglycemia.
Am J Pathol. 2012; 180(1): 153-164.
Doi: 10.1016/j.ajpath.2011.09.012
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- Führende Autor*innen der Med Uni Graz
- Fröhlich Julia
- Huppertz Berthold
- Co-Autor*innen der Med Uni Graz
- Abuja Peter Michael
- Desoye Gernot
- König Julia Maria
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Antimetabolites - pharmacology
- Antioxidants - pharmacology
- Cell Proliferation -
- Cells, Cultured -
- Diabetes, Gestational - metabolism Diabetes, Gestational - physiopathology
- Enzyme Inhibitors - pharmacology
- Female -
- Humans -
- Hydrogen Peroxide - metabolism
- Hyperglycemia - embryology Hyperglycemia - metabolism Hyperglycemia - physiopathology
- MAP Kinase Signaling System - physiology
- Mitochondria - enzymology
- Mitogen-Activated Protein Kinases - metabolism
- Oxygen - pharmacology
- Pregnancy -
- Pregnancy Trimester, First -
- Protein Kinase Inhibitors - pharmacology
- Reactive Oxygen Species - metabolism
- Trophoblasts - metabolism Trophoblasts - physiology
- Up-Regulation -