BACKGROUND: @entity117 ( @entity1281 ) is a @entity35 teratogen, and exposures on gestational days (GDs) 9 and 10 induce diaphragm, @entity601 . @entity1281 inhibits members of the cyclooxygenase (COX) family and potentially members of the carbonic anhydrase (CA) family. The objective of this study was to determine whether the mRNA developmental expression pattern for any COX or CA isoform was consistent with a model in which @entity1281 teratogenicity is mediated through direct interaction with one of these enzymes within embryos or within the adjacent ectoplacental cone (EPC) or yolk sac. METHODS: Staged embryos, over a range (GD 9.5-12) that included @entity1281 -sensitive and @entity1281 -insensitive stages of organogenesis, were assayed for COX and CA mRNA levels by three techniques: microarrays; in situ hybridization quantitated by a micro-imager; and quantitative reverse transcription polymerase chain reaction. @entity1281 - and vehicle-treated embryos also were compared to determine whether inhibition led to upregulated COX or CA mRNA expression. RESULTS: @entity4665 mRNA was undetectable in embryos throughout organogenesis by any assay (although it was abundant in EPC). In contrast, @entity9774 mRNA was moderately abundant in embryos throughout organogenesis. One CA isoform, @entity16711 , demonstrated developmentally regulated embryonic mRNA expression that coincided with @entity1281 sensitivity @entity1281 exposure failed to induce upregulation of any of these mRNAs. CONCLUSIONS: Although @entity1281 may affect the embryo indirectly through interaction with @entity4665 within EPC, failure to detect embryonic @entity4665 mRNA argues against @entity4665 functioning as a direct mediator of @entity1281 teratogenic activity in induction of cardiac, diaphragm, and @entity601 . Correlation of @entity9774 and @entity16711 expression with @entity1281 sensitivity suggested that embryonic @entity9774 and possibly @entity16711 are much more likely candidates for mediators of @entity1281 developmental @entity137 .

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

@entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity117 :: ('MESH:D001241', 'Chemical') :: ['Acetylsalicylic acid'] @entity16711 :: ('29242(Tax:10116)', 'Gene') :: ['CA4', 'CA-4'] @entity9774 :: ('26195(Tax:10116)', 'Gene') :: ['COX-1'] @entity601 :: ('MESH:D009436', 'Disease') :: ['cardiac, and midline defects', 'midline defects'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity4665 :: ('26198(Tax:10116)', 'Gene') :: ['COX-2'] @entity1281 :: ('CHEBI:15365', 'Chemical') :: ['ASA']
@entity35 :: (10116,Species) :: ['Rat']
