TY - JOUR
AU1 - Thrikawala, Savini
AU2 - Mesmar, Fahmi
AU3 - Bhattacharya, Beas
AU4 - Muhsen, Maram
AU5 - Mukhopadhyay, Srijita
AU6 - Flores, Sara
AU7 - Upadhyay, Sanat
AU8 - Vergara, Leoncio
AU9 - Gustafsson, Jan-Åke
AU1 - Williams, Cecilia
AU1 - Bondesson, Maria
AB - Triazoles are a major group of azole fungicides commonly used in agriculture, and veterinary and human medicine. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. We hypothesized that triazoles used as pesticides in agriculture also pose a risk of causing skeletal malformations in developing embryos. In this study, teratogenic effects of three commonly used triazoles, cyproconazole, paclobutrazol, and triadimenol, were investigated in zebrafish, Danio rerio. Exposure to the triazole fungicides caused bone and cartilage malformations in developing zebrafish larvae. Data from whole-embryo transcriptomics with cyproconazole suggested that exposure to this compound induces adipogenesis while repressing skeletal development. Confirming this finding, the expression of selected bone and cartilage marker genes were significantly downregulated with triazoles exposure as determined by quantitative PCR. The expression of selected adipogenic genes was upregulated by the triazoles. Furthermore, exposure to each of the three triazoles induced adipogenesis and lipid droplet formation in vitro in 3T3-L1 pre-adipocyte cells. In vivo in zebrafish larvae, cyproconazole exposure caused lipid accumulation. These results suggest that exposure to triazoles promotes adipogenesis at the expense of skeletal development, and thus they expand the chemical group of bona fide bone to fat switchers.
TI - Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish
JF - Toxicological Sciences
DO - 10.1093/toxsci/kfad031
DA - 2023-03-23
UR - https://www.deepdyve.com/lp/oxford-university-press/triazole-fungicides-induce-adipogenesis-and-repress-osteoblastogenesis-u09FcsrdKl
SP - 119
EP - 130
VL - 193
IS - 2
DP - DeepDyve
ER -