Chicken embryonic cerebral cortex exposed to two doses of PFHxS.

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, mRNA expression and circulating free thyroxine levels). Based on these findings, we hypothesize that PFHxS exposure interferes with TH-dependent neurodevelopmental pathways. The present study investigates global transcriptional profiles of cerebral cortex tissue from chicken embryos following exposure to a solvent control, 890 or 38,000 ng PFHxS/g egg (n=4-5 per group); doses which lead to the adverse effects above. PFHxS significantly alters the expression (≥1.5-fold, p≤0.001) of 11 transcripts at the low dose (LD; 890 ng/g) and 101 transcripts at the high dose (HD; 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 signalling. 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, while TH-independent mechanisms include gap junction intercellular communication. Reference Design. Reference = pool of equal parts of all control and treated samples. Control groups and 2 treatment groups. Control samples were chicken embryonic cerebral cortex exposed DMSO only (solvent). Treatments were: chicken embryonic cerebral cortex exposed to 890 ng/g PFHxS (LD) and 38,000 ng/g PFHxS (HD).