He CY, ZH Zuo, XA Shi, RX Li, DL Chen, X Huang, YX Chen and CG Wang.Aquatic Toxicology, 2011. 101: 335-341.

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

Fig. 2 Exposure to BaP for 7 days resulted in neurocranial and craniofacial skeletal defects inSebastiscus marmoratusembryos. Lateral (A-D) and ventral (E-H) views of head of larvae. Control larvae (A and E) displayed a normal craniofacial skeleton; the 0.05 nmol/L BaP exposure (B and F) showed no adverse effect to skeletal development and several skeletons, such as the circumorbital series and the otic capsule, developed faster than those in the control group. Exposure to 0.5 (C and G) or 5 nmol/L BaP (D and H) led to shortened optic and otic capsules; shortened ceratobranchia and hyoid arches (C and D); and warping of Meckel’s cartilage resulting in a shorter lower jaw (G and H). Abbreviations: ch, ceratohyal; cb3-7, ceratobranchial 3-7 (branchial arches); cs, circumorbital series; ep, ethmoid plate (neurocranium); mc, Meckel’s cartilage (lower jaw); ot, optic capsule; pq, palatoquadrate (upper jaw); sy, symplectic; tb, trabecular (neurocranium). Scale bars are 100µm.