title: Hyperglycemia perturbs biochemical networks in human trophoblast BeWo cells.
abstract: Determining the effects of hyperglycemia on gene expression in placental trophoblast is important to gain a better understanding of how diabetes adversely affects pregnancy. In this study, we examined whether exposure to high glucose during forskolin-induced differentiation affects gene expression in differentiated trophoblasts. Human trophoblast BeWo cells were differentiated under low glucose (LG: 11 mM) or high glucose (HG: 25 mM) conditions. Gene expression was analyzed using a GeneChip system and the obtained data were analyzed using Ingenuity Pathways Analysis. In HG conditions, there were marked alterations in gene expression in differentiated BeWo cells compared with LG conditions. In particular, BeWo cells responded to HG with major changes in the expression levels of cell cycle- and metabolism-related genes. We selected the aromatase gene for further investigation of the molecular mechanisms. Mannitol or 3-O-methylglucose did not mimic the expression changes caused by HG, indicating that the effect of glucose was not due to a difference in osmotic pressure, and that glucose metabolism plays an essential role in inducing the HG effects. Cotreatment with N-acetylcysteine reduced the effect of HG on aromatase gene expression, suggesting that hyperglycemia may perturb biochemical networks because of the elevation of oxidative stress. Overall, our results will aid further understanding of the effect of diabetes on the regulation of trophoblast differentiation and function.
authors.affiliation: Department of Public Health, Faculty of Medicine, University of Toyama, Sugitani, Toyama, Japan. inadera@med.u-toyama.ac.jp
authors.forename: Hidekuni
authors.initials: H
authors.lastname: Inadera
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Tachibana
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takasaki
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tatematsu
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimomura
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D001669:Biochemical Phenomena / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000187:drug effects* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology
chemical_list: D001141:Aromatase; D005947:Glucose; D000111:Acetylcysteine