Markedly increased constitutive CYP1A1 mRNA levels in the fertilized ovum of the mouse.
Using a highly sensitive RT-PCR technique that measures mRNA (cDNA)-to-DNA ratios, we are able to detect constitutive CYP1A1 mRNA in adult mouse liver as well as in the oocyte. Twelve hours after fertilization of the ovum, there is a more than 100-fold increase in constitutive CYP1A1 mRNA levels; this dramatic increase completely disappears by the 2-cell stage at gestational day 1.5 (GD1.5), as well as in the blastocyst at GD3.5. The CYP1A1 enzyme has been shown to remove an endogenous ligand for the Ah receptor (AHR), and the AHR is known to play a role in cell cycle regulation and apoptosis. We therefore postulate that this striking abundance of constitutive CYP1A1 mRNA in the fertilized ovum at GD0.5 might be important for maintaining sufficient amounts of the CYP1A1 enzyme during the transition from maternal to zygotic control (GD0.5 to GD1.5 embryo); availability of catalytically active CYP1A1 would ensure that any (exogenous or endogenous) AHR ligand be rapidly degraded, so that all undesirable AHR-mediated gene transcription would be prevented during these very critical moments of early mammalian embryogenesis.
Dey
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Center for Environmental Genetics and the Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267-0056, USA.
Nebert
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D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000201:enzymology; D002453:Cell Cycle; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005314:Embryonic and Fetal Development; D005091:Exons; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000201:enzymology; D010063:Ovum / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013480:Superovulation; D014158:Transcription, Genetic; D015053:Zygote / Q000201:enzymology*
D008024:Ligands; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1