Phenanthrene causes ocular developmental toxicity in zebrafish embryos and the possible mechanisms involved.
Recent studies show that polycyclic aromatic hydrocarbons (PAHs) may be a candidate cause of developmental defects of the retina, but the mechanism is still unclear. We evaluated the mechanism(s) underlying PAH-induced retinal development defects due to exposure to environmental concentrations of Phenanthrene (Phe) in zebrafish. We found that exposure to environmental concentrations of Phe caused obvious morphological changes, developmental retardation, apoptosis, and reduction of cell proliferation in the retina. Our results indicated that Phe could cause visual system developmental defects. Phe exposure up-regulated aryl hydrocarbon receptor (AhR) and microphthalmia-associated transcription factor (Mtif) expression, and down-regulated zinc finger E-box binding homeobox 1 (Zeb1) and paired box 6 (Pax6). Moreover, we demonstrated that AhR was a repressor of Zeb1. We propose that Phe's ocular toxicity is mediated by up-regulating AhR, which then down-regulates Zeb1, in turn inducing Mitf expression while inhibiting Pax6 expression.
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
Lixing
L
Huang
Chonggang
C
Wang
Youyu
Y
Zhang
Meifang
M
Wu
Zhenghong
Z
Zuo
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004625:Embryo, Nonmammalian; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010616:Phenanthrenes / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
D005136:Eye Proteins; D018398:Homeodomain Proteins; D051739:Microphthalmia-Associated Transcription Factor; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D010616:Phenanthrenes; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; D014157:Transcription Factors; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; D000071799:Zinc Finger E-box-Binding Homeobox 1; C497237:mitfa protein, zebrafish; C583292:zeb1b protein, zebrafish; C031181:phenanthrene; D053148:Caspase 3
AhR/Zeb1/Mitf/Pax6; Ocular developmental toxicity; Phenanthrene; Zebrafish