The unique characteristics of the placental transcriptome and the hormonal metabolism enzymes in placenta

• The transcriptome in placenta is clearly dissimilar to its liver equivalent.
• The placenta should be viewed as an atypical “extrahepatic” tissue.
• The main hepatic xenobiotic metabolism CYP families are not expressed in placenta at term.
• The transcription factors expressed in placenta are not associated with CYPs related to xenobiotic metabolism.
• Placental responses to endocrine disrupters are mainly dependent on a unique set of transcription factors.

The placenta regulates the passage of both endogenous and xenobiotic compounds to the fetus during pregnancy. A small number of xenobiotic metabolizing CYP enzymes are constantly expressed in placenta, those include CYP19A1 which mainly converts androgens to estrogens, and CYP1A1 whose substrates include steroid hormones and xenobiotics. We performed an analysis of co-expression of xenobiotic metabolizing enzyme-coding genes and transcription factors in placenta and in 86 other tissues to discern the unique characteristics of the placental transcriptome. Transcription factors (TFs) driving the expression of proteins involved in phase I and II xenobiotic metabolism in the liver were not expressed in the placenta, nor were the bulk of xenobiotic metabolizing hepatic CYP enzymes. In contrast, TFs whose co-expression correlated with CYP1A1, i.e. AHR, PPARG, and CEBPB were highly expressed in placenta. The placenta is a hormonal tissue, and one needs to maintain the tissue-specific focus by removing the hepatic spectacles.