Expression Regulation of Hox Genes by Perfluorochemicals in Mouse Liver

Abstract

Homeobox (Hox) genes encode homeodomain proteins, which play important roles in the development and morphological diversification of plants and animals. Perfluorochemicals (PFCs), which are the persistent environmental pollutants and frequently detected in human blood, can interfere with animal development. PFCs produce numerous hepatic adverse effects, such as increased peroxisomes, hepatomegaly and altered lipid metabolism, primarily via activation of peroxisome proliferator‐activated receptors (PPARs) and/or constitutive androstane receptor (CAR). No study has reported that PFCs can regulate the expression of Hox genes. This study was designed to determine the expression regulation of Hox and paraHox genes by perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) in mouse liver. A single dose of 0.1 mmole/kg PFOA, PFNA and PFDA was intraperitoneally administered to adult male wild‐type, and age‐matched male PPARα‐null and male CAR‐null mice (n=6/treatment). Four days later, mouse livers were collected and processed. Messenger RNA expression of Hox genes (including Hox‐a to ‐d subfamily members) and paraHox genes (including Gsx, Pdx, and Cdx gene family members) were determined. Our results showed that PFOA, PFNA, and PFDA all induced mRNA expression of Hoxb7, c5, d10 and Zeb2 in wild‐type mouse liver, but not in PPARα‐null mouse liver. We further showed that PFNA induced mRNA expression of Hoxa5, b7, c5, c8, and d10 in livers of wild‐type and CAR‐null mice, but not in PPARα‐null mouse liver, indicating a PPARα‐dependent mechanism. Furthermore, knocking‐out of PPARα or CAR in mouse liver decreased constitutive mRNA expression of Hoxc5. Wy‐14643, a classical PPARα agonist, induced mRNA expression of Hoxc5, but not of Hoxa5, b7 or d10 in wild‐type mouse liver. 1,4‐bis‐[2‐(3,5,‐dichloropyridyloxy)] benzene (TCPOBOP), a classical CAR agonist, also induced mRNA expression of Hoxc5, but not of Hoxa5, b7 or d10 in wild‐type mouse liver. Messenger RNA expression of studied paraHox genes were not apparently altered by PFCs in mouse liver. In conclusion, perfluorochemicals induced mRNA expression of certain Hox genes such as Hoxc5, maybe via activation of PPARα and/or CAR.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.