Transcriptional profiles in the cerebral hemisphere of chicken embryos following in ovo perfluorohexane sulfonate exposure.
In a recent egg injection study, we showed that in ovo exposure to perfluorohexane sulfonate (PFHxS) affects the pipping success of developing chicken (Gallus gallus domesticus) embryos. We also found evidence of thyroid hormone (TH) pathway interference at multiple levels of biological organization (i.e., somatic growth, messenger RNA expression, and circulating free thyroxine levels). Based on these findings, we hypothesize that PFHxS exposure interferes with TH-dependent neurodevelopmental pathways. This study investigates global transcriptional profiles in cerebral hemispheres of chicken embryos following exposure to a solvent control, 890 or 38,000 ng PFHxS/g egg (n = 4-5 per group); doses that lead to the adverse effects indicated above. PFHxS significantly alters the expression (≥ 1.5-fold, p ≤ 0.001) of 11 transcripts at the low dose (890 ng/g) and 101 transcripts at the high dose (38,000 ng/g). Functional enrichment analysis shows that PFHxS affects genes involved in tissue development and morphology, cellular assembly and organization, and cell-to-cell signaling. Pathway and interactome analyses suggest that genes may be affected through several potential regulatory molecules, including integrin receptors, myelocytomatosis viral oncogene, and CCAAT/enhancer-binding protein. This study identifies key functional and regulatory modes of PFHxS action involving TH-dependent and -independent neurodevelopmental pathways. Some of these TH-dependent mechanisms that occur during embryonic development include tight junction formation, signal transduction, and integrin signaling, whereas TH-independent mechanisms include gap junction intercellular communication.
Environment Canada, National Wildlife Research Centre, Ottawa, Ontario, Canada K1A 0H3.
Cristina G
CG
Cassone
Jessica J
JJ
Taylor
Jason M
JM
O'Brien
Andrew
A
Williams
Carole L
CL
Yauk
Doug
D
Crump
Sean W
SW
Kennedy
D000818:Animals; D054022:Cerebrum / Q000187:drug effects*; D002642:Chick Embryo; D005466:Fluorocarbons; D020869:Gene Expression Profiling; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013451:Sulfonic Acids / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects*
D005466:Fluorocarbons; D012333:RNA, Messenger; D013451:Sulfonic Acids; C471071:perfluorohexanesulfonic acid