The brominated flame retardant, 1,2,5,6-tetrabromocyclooctane (TBCO), causes multigenerational effects on reproductive capacity of Japanese medaka (Oryzias latipes)

Exposure of fishes to endocrine disrupting chemicals (EDCs) during early development can induce multigenerational and transgenerational effects on reproduction. Both in vivo and in vitro studies have demonstrated that the brominated flame retardant, 1,2,5,6-tetrabromocyclooctane (TBCO), is an EDC. The present study investigated whether TBCO has mutigenerational and/or transgenerational effects on the reproductive performance of Japanese medaka (Oryzias latipes). Sexually mature fish (F0 generation) were fed either a control diet or a low (40.6 μg/g) or high (1034.4 μg/g) diet containing TBCO, and three generations of embryos were reared to determine reproductive performance using a standard 21-day reproduction assay. Concentrations of TBCO in eggs (F1 generation) from F0 fish given the low and high diets were 711.3 and 2535.5 ng/g wet weight, respectively. Cumulative fecundity of the F1 generation in the low and high treatment were reduced by 33.9% and 33.3%, respectively, compared to the control. In the F2 generation, cumulative fecundity of the low treatment returned to the level of the controls, but the high treatment was decreased by 29.8%. There was no decrease in cumulative fecundity in the F3 generation compared to the controls. Mechanistically, mRNA abundances of cholesterol side chain cleavage enzyme (cyp11a), aromatase (cyp19a), and luteinizing hormone receptor (lhr) were differentially expressed in gonads from F1 females, suggesting that TBCO might cause developmental reprogramming that disrupts steroidogenesis leading to decreased fecundity. However, concentrations of E2 in plasma and mRNA abundance of vitellogenin in liver were not significantly different compared to controls suggesting a mechanism other than disruption of steroidogenesis or vitellogenesis. Mechanistically, no effects were observed in the F2 or F3 generation. Overall, results suggest that TBCO has multigenerational effects on the reproductive performance of Japanese medaka. However, no transgenerational effects were observed as the F3 generation fully recovered. The mechanism by which multigenerational effects were induced is not known.