McNabb-Kelada, N.; Burke, T.; Jayaraman, S.; Mills, L.; De La Torre, A.; Francoeur, M.; Schraeder, H.; Nacci, D.; Clark, B.; Whitehead, A.

Environmental pollutants can have lasting effects that extend beyond the exposure period, potentially impacting multiple generations. Despite the widespread presence of polybrominated diphenyl ether (PBDE) flame retardants in the environment including oceans globally, there is limited understanding of their potential for multigenerational toxicity. We investigated whether exposures to 2,2\',4,4\',5-pentaBDE (BDE-99), a predominant PBDE congener, can induce neurobehavioral and molecular effects across two generations using the marine vertebrate model fish Fundulus heteroclitus (Atlantic killifish). To assess how exposure route influences outcomes, we conducted two complementary experiments: in the progenitor exposure experiment, adult fish were exposed to BDE-99 through diet, leading to maternal transfer into F1 eggs, while in the direct embryonic exposure experiment, embryos were exposed to BDE-99 via waterborne exposure, achieving comparable embryonic doses. Both exposure routes resulted in altered photomotor responses in F1 larvae, but additional effects differed by exposure route. In the progenitor exposure, maternally exposed F1 juvenile fish exhibited reduced anxiety-like behavior and changes in brain gene expression, while in the direct embryonic exposure, F0 fish showed no detectable effects within their generation but caused behavioral alterations in F1 descendants. The lack of effects in direct F0 individuals suggests that neurobehavioral effects observed in maternally exposed F1 fish were not solely due to BDE-99 transfer but were influenced by additional maternal factors. In the progenitor exposure, neither behavioral nor gene expression effects persisted in the F2 generation. We conclude that maternal influences play a key role in shaping multigenerational effects of BDE-99 exposure, as indicated by the strong effects observed in maternally exposed F1 fish but not in F2 descendants, as well as the differences between maternally exposed fish and those exposed to comparable doses of BDE-99 alone.