Identification of differentially expressed genes in fetal rat forebrain exposed to a teratogen by cDNA microarray analysis.
In an attempt to understand the molecular basis underlying the neural tube defects induced by the teratogen, cyclophosphamide (CP), cDNA microarray analysis was carried out in neural tubes of embryos derived from normal and CP-treated rats. Genes found to have altered expression levels in CP-treated group were clustered into groups on the basis of their biological functions. The expression profile of different genes involved in transcription of molecules related to cell adhesion, inflammation, metabolism and neurotrophic factors pathways as well as in still undefined processes was differentially affected by the teratogen treatment. The most remarkable change was the up-regulation of genes related to an inflammatory process dominated by the fetal brain macrophages viz. amoeboid microglia. Amoeboid microglia/brain macrophage expansion, based on gene expression and histological analysis, was found to be vigorous at the subventricular region. The present results suggest that a vigorous inflammatory response involving amoeboid microglia/brain macrophages primarily is an important component in CP-induced prenatal development disorder.
Dheen
S T
ST
Molecular Neurobiology Laboratory, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. antstd@nus.edu.sg
Hao
A J
AJ
Fu
J
J
Gopalakrishnakone
P
P
Ling
E A
EA
D000818:Animals; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000235:genetics; D037102:Lectins / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016548:Prosencephalon / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013723:Teratogens / Q000633:toxicity*; D013997:Time Factors
D037102:Lectins; D012333:RNA, Messenger; D013723:Teratogens; D016173:Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D016186:Receptor, Macrophage Colony-Stimulating Factor; D020170:Caspase 1