Rat embryos express transcripts for cyclooxygenase-1 and carbonic anhydrase-4, but not for cyclooxygenase-2, during organogenesis.

摘要: BACKGROUND: Acetylsalicylic acid (ASA) is a rat teratogen, and exposures on gestational days (GDs) 9 10 induce diaphragm, cardiac, midline defects. ASA inhibits members of the cyclooxygenase (COX) family potentially carbonic anhydrase (CA) family. The objective this study was to determine whether mRNA developmental expression pattern for any COX or CA isoform consistent with model in which teratogenicity mediated through direct interaction one these enzymes within embryos adjacent ectoplacental cone (EPC) yolk sac. METHODS: Staged embryos, over range (GD 9.5–12) that included ASA-sensitive ASA-insensitive stages organogenesis, were assayed levels by three techniques: microarrays; situ hybridization quantitated micro-imager; quantitative reverse transcription polymerase chain reaction. ASA- vehicle-treated also compared inhibition led upregulated expression. RESULTS: COX-2 undetectable throughout organogenesis assay (although it abundant EPC). In contrast, COX-1 moderately organogenesis. One isoform, CA-4, demonstrated developmentally regulated embryonic coincided sensitivity. exposure failed upregulation mRNAs. CONCLUSIONS: Although may affect embryo indirectly EPC, failure detect argues against functioning as mediator teratogenic activity induction Correlation CA-4 sensitivity suggested possibly are much more likely candidates mediators toxicity. Birth Defects Research (Part B) 68:57–69, 2003. © 2003 Wiley-Liss, Inc.