title: Insight into the transgenerational effect of benzo[a]pyrene on bone formation in a teleost fish (Oryzias latipes).
abstract: Recent cross-generational studies in teleost fish have raised the awareness that high levels of benzo[a]pyrene (BaP) could affect skeletal integrity in the directly exposed F0 and their F1-F2. However, no further details were provided about the causes for abnormalities on the molecular and cellular level and the persistence of such sub-organismal impairments at the transgenerational scale (beyond F2). Adult Oryzias latipes were exposed to 1μg/L BaP for 21days. The F1-F3 were examined for skeletal deformities, histopathological alterations of vertebral bodies and differential expression of key genes of bone metabolism. Significant increase of dorsal-ventral vertebral compression was evident in ancestrally exposed larvae. Histopathological analysis revealed abnormal loss of notochord sheath, a lack of notochord epithelial integrity, reduced bone tissue and decreased osteoblast abundance. A significant downregulation of ATF4 and/or osterix and a high biological variability of COL10, coupled with a significant deregulation of SOX9a/b in the F1-F3 suggest that ancestral BaP exposure most likely perturbed chordoblasts, chondroblast and osteoblast differentiation, resulting in defective notochord sheath repair and rendering the vertebral column more vulnerable to compression. The present findings provide novel molecular and cellular insights into BaP-induced transgenerational bone impairment in the unexposed F3. From the ecological risk assessment perspective, BaP needs to be regarded as a transgenerational skeletal toxicant, which exerts a far-reaching impact on fish survival and fitness. Given that basic mechanisms of cartilage/bone formation are conserved between medaka and mammals, the results may also shed light on the potential transgenerational effect of BaP on the genesis of skeletal diseases in humans.
authors.affiliation: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Frauke
authors.initials: F
authors.lastname: Seemann
authors.affiliation: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Drew R
authors.initials: DR
authors.lastname: Peterson
authors.affiliation: Department of Biology, Ghent University, Ledeganckstraat 35, B-9000 Ghent, Belgium.
authors.forename: P Eckhard
authors.initials: PE
authors.lastname: Witten
authors.affiliation: Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
authors.forename: Bao-Sheng
authors.initials: BS
authors.lastname: Guo
authors.affiliation: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Adamane H
authors.initials: AH
authors.lastname: Shanthanagouda
authors.affiliation: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Rui R
authors.initials: RR
authors.lastname: Ye
authors.affiliation: Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Hong Kong; Shenzhen Key Laboratory for the Sustainable Use of Marine Biodiversity, Research Centre for the Oceans and Human Health, City University of Hong Kong, Shenzhen Research Institute, Shenzhen 518057, China. Electronic address: bhdwtau@cityu.edu.hk.
authors.forename: Doris W T
authors.initials: DWT
authors.lastname: Au
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000009:adverse effects*; D002356:Cartilage / Q000187:drug effects; D007814:Larva / Q000187:drug effects / Q000502:physiology; D009990:Oryzias / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000009:adverse effects
chemical_list: D014874:Water Pollutants, Chemical; D001564:Benzo(a)pyrene
keywords: Bone metabolism; Cigarette smoke; Cross-generational effects; Japanese medaka; Multigenerational effects; Notochord sheath; Oryzias latipes; Osterix; PAHs; Sox 9; Teleost