Comparative thyroid disruption by o,p'-DDT and p,p'-DDE in zebrafish embryos/larvae

Highlights: • o,p'-DDT and p,p′-DDE cause developmental toxicity in zebrafish larvae. • o,p'-DDT exposure significantly increased whole-body thyroid hormone levels. • p,p′-DDE exposure significantly decreased whole-body thyroid hormone levels. • The gene expression patterns of HPT axis were changed after exposure to either o,p'-DDT or p,p′-DDE. -- Abstract: 1,1-Trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethane (o,p'-DDT) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p′-DDE) cause thyroid disruption, but the underlying mechanisms of these disturbances in fish remain unclear. To explore the potential mechanisms of thyroid dysfunction caused by o,p'-DDT and p,p′-DDE, thyroid hormone and gene expression levels in the hypothalamic-pituitary-thyroid (HPT) axis were measured, and the developmental toxicity were recorded in zebrafish larvae. Zebrafish embryos/larvae were exposed to o,p'-DDT (0, 0.28, 2.8, and 28 nM; or 0, 0.1, 1, and 10 μg/L) and p,p′-DDE (0, 1.57, 15.7, and 157 nM; or 0, 0.5, 5, and 50 μg/L) for 7 days. The genes related to thyroid hormone synthesis (crh, tshβ, tg, nis and tpo) and thyroid development (nkx2.1 and pax8) were up-regulated in both the o,p'-DDT and p,p′-DDE exposure groups. Zebrafish embryos/larvae exposed to o,p'-DDT showed significantly increased total whole-body T4 and T3 levels, with the expression of ugt1ab and dio3 being significantly down-regulated. However, the p,p′-DDE exposure groups showed significantly lowered whole-body total T4 and T3 levels, which were associated with up-regulation and down-regulation expression of the expression of dio2 and ugt1ab, respectively. Interestingly, the ratio of T3 to T4 was significantly decreased in the o,p'-DDT (28 nM) and p,p′-DDE (157 nM) exposure groups, suggesting an impairment of thyroid function. In addition, reduced survival rates and body lengths and increased malformation rates were recorded after treatment with either o,p'-DDT or p,p′-DDE. In summary, our study indicates that the disruption of thyroid states was different in response to o,p'-DDT and p,p′-DDE exposure in zebrafish larvae.