Multi- and Transgenerational Developmental Impairments Are Induced by Decabromodiphenyl Ethane (DBDPE) in Zebrafish Larvae

Abstract

A novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a ubiquitous emerging pollutant; hence, the knowledge of its long-term toxic effects and underlying mechanism would be critical for further health risk assessment. In the present study, the multi-and transgenerational toxicity of DBDPE was investigated in zebrafish upon a life cycle exposure at environmentally relevant concentrations. The significantly increased malformation rate and declined survival rate specifically occurred in unexposed F2 larvae suggested transgenerational development toxicity by DBDPE. The changing profiles revealed by transcriptome and DNA methylome confirmed an increased susceptibility in F2 larvae and figured out potential disruptions of glycolipid metabolism, mitochondrial energy metabolism, and neurodevelopment. The changes of biochemical indicators such as ATP production confirmed a disturbance in the energy metabolism, whereas the alterations of neurotransmitter contents and light−dark stimulated behavior provided further evidence for multi-and transgenerational neurotoxicity in zebrafish. Our findings also highlighted the necessity for considering the long-term impacts when evaluating the health of wild animals as well as human beings by emerging pollutants.

Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae

“…Glu is known as a major excitatory neurotransmitter, while GABA usually acts as an inhibitory neurotransmitter . Previous studies have mentioned that PBDEs, such as PBDE-47 and PBDE-99, have the ability to alter the function of GABA receptors and caused hyperactivity in mice. , A recent study reported elevated Glu and GABA levels followed by increased transcription of the Glu receptor and decreased transcription of the GABA receptor in zebrafish larvae exposed to DBDPE at environmentally relevant concentrations, indicating combined action of these neurotransmitters in behavioral control . Similarly, in the current study, we also observed an increase in the mRNA levels of the Glu receptor, ionotropic N -methyl- d -aspartate 3A ( grin 3 a ), and those of GABA type A receptor subunits alpha3 and 6 ( gabra 3 and gabra 6) were decreased in zebrafish larvae ( P < 0.05, Figure C).…”

“…Taken together, the untargeted metabolomics results in this study figured out obviously different metabolomic profiles upon DBDPE exposure, which may affect the pathways involving glycolipid metabolism, oxidative phosphorylation and oxidative stress as further validated. Similar effects have been widely reported in previous studies of traditional BFRs (e.g., BDE-47, BDE-100, and BDE-209), most of which suggested a potential mechanism related with mitochondrial injury. ,, Our recent study using multiomics also provided important clues for mitochondrial dysfunctions in DBDPE-induced adverse effects in zebrafish larvae . Therefore, we next would like to verify the damage on the mitochondrial function and its role in DBDPE-induced adverse effects.…”

“…A previous study indicated that DBDPE inhibited oxidative phosphorylation in Pleurotus ostreatus . Similarly, our recent study also showed that DBDPE exposure significantly inhibited the transcription level of oxidative phosphorylation signaling pathways in the offspring of zebrafish . Typically, the levels of NADH were significantly increased ( P < 0.05, Figure D), while the NAD + /NADH ratio was significantly decreased ( P < 0.05, Figure E) upon DBDPE exposure.…”

“…22,55,56 Our recent study using multiomics also provided important clues for mitochondrial dysfunctions in DBDPEinduced adverse effects in zebrafish larvae. 17 Therefore, we next would like to verify the damage on the mitochondrial function and its role in DBDPE-induced adverse effects.…”

“…Our previous study indicated that DBDPE was prone to be accumulated in the brain of adult female zebrafish and caused neurotoxicity as indicated by disturbed calcium homeostasis and a decreased total swimming distance . In a recent study, life cycle exposure to DBDPE at environmentally relevant concentrations caused multi- and transgenerational developmental toxicity in zebrafish larvae . It is noteworthy that the transcriptome and methylome results both figured out potential effects on material and energy metabolism.…”