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Polychlorinated biphenyls affect gene expression in the rabbit preimplantation embryo
Author(s) -
Kietz Silke,
Fischer Bernd
Publication year - 2003
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.10226
Subject(s) - biology , aryl hydrocarbon receptor , microbiology and biotechnology , cyp1b1 , gene expression , aryl hydrocarbon receptor nuclear translocator , cytochrome p450 , gene , embryo , glutathione , transcription factor , enzyme , biochemistry
Polychlorinated biphenyls (PCBs) have been shown to be embryotoxic. The mechanism(s) of action is not clearly understood. The toxic effects could be either direct or indirect. Furthermore, PCB congeners vary in their toxic potential. They can be classified in coplanar PCBs binding to the transcription factor aryl hydrocarbon receptor (AhR), which induce subsequent changes in gene expression, and noncoplanar PCBs exhibiting AhR‐independent effects. In order to investigate possible mechanisms, 5 and 6 days old preimplantation rabbit embryos were exposed in vitro to low levels of coplanar (PCB 77, 126, and 169) or noncoplanar PCBs (PCB 28, 52, 101, 118, 138, 153, and 180). The PCB effects were studied by semiquantitative RT‐PCR analysis of AhR target genes (cytochrome P450 (CYP) 1A1, 1A2, UDP‐glucuronosyl transferase 1, glutathione S‐transferase π1 and aldehyde dehydrogenase) and dioxin‐responsive genes (IL 1β, PAI 2, Cox 2, TGFα, EGF, erbB 1–4, c‐fos, c‐jun, HSP 90, cyclophilin 40), and by differential display (DD) RT‐PCR. CYP 1B1 mRNA and AhR protein were localized by in situ hybridization and immunohistochemistry, respectively. From the AhR target genes studied only CYP 1B1, and cyclooxygenase 2 showed an increase in mRNA levels after coplanar and noncoplanar PCB. Interleukin 1β and plasminogen activator inhibitor 2 were downregulated. CYP 1B1 mRNA showed a stage specific inducibility at day 6, but not at day 5. By DD RT‐PCR we identified six new genes previously not reported to be regulated by PCBs. The mRNAs encoding the subunits 1, 2, 4, and 5 of the NADH ubiquinone oxidoreductase and β‐globin showed a decrease, whereas trichohyalin mRNA was increased after PCB exposure. Coplanar and noncoplanar PCB congeners elicited similar responses on the mRNA levels of the studied genes. Exposure to coplanar PCBs did not result in the AhR being translocated to the nucleus. Our results show that (i) PCBs induce changes in gene expression in rabbit day 5 and 6 preimplantation embryos and imply (ii) that the transcriptional changes observed were not mediated by the nuclear AhR. Mol. Reprod. Dev. 64: 251–260, 2003. © 2003 Wiley‐Liss, Inc.