Developmental exposure to BDE-99 hinders cerebrovascular growth and disturbs vascular barrier formation in zebrafish larvae

Zhong, Xingwu; Kang, Jianmeng; Qiu, Jiajun; Yang, Wenhan; Wu, Jingwei; Ji, Di; Yu, Yuejin; Ke, Weijian; Shi, Xiongjie; Wei, Yanhong

doi:10.1016/j.aquatox.2019.105224

Cited by 14 publications

(4 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No significant change was observed in curved tails, short tails, or yolk sac edema (Figure S3), whereas a marked increase in pericardial edema was exhibited in the 30,000 ng/L group (Figure S2F). The results suggest heightened susceptibility of the cardiovascular system to BDP exposure, as we expected according to our previous studies, , implicating a necessity of comprehensive and precise assessment of vascular morphology.…”

Section: Results and Discussionsupporting

confidence: 82%

Parental Exposure to Environmentally Relevant Concentrations of Bisphenol-A Bis(diphenyl phosphate) Impairs Vascular Development in Offspring through DNA/RNA Methylation-Dependent Transmission

Wang,

Xu,

Luo

et al. 2023

Environ. Sci. Technol.

Self Cite

View full text Add to dashboard Cite

Bisphenol-A bis(diphenyl phosphate) (BDP) has been increasingly detected in indoor environmental and human samples. Little is known about its developmental toxicity, particularly the intergenerational effects of parental exposure. In this study, adult zebrafish were exposed to BDP at 30–30,000 ng/L for 28 days, with results showing that exposure did not cause a transfer of BDP or its metabolites to offspring. Vascular morphometric profiling revealed that parental exposure to BDP at 30 and 300 ng/L exerted significant effects on the vascular development of offspring, encompassing diverse alterations in multiple types of blood vessels. N6-Methyladenosine (m6A) methylated RNA immunoprecipitation sequencing of larvae in the 300 ng/L group revealed 378 hypomethylated and 350 hypermethylated m6A peaks that were identified in mRNA transcripts of genes crucial for vascular development, including the Notch/Vegf signaling pathway. Concomitant changes in 5 methylcytosine (m5C) DNA methylation and gene expression of m6A modulators (alkbh5, kiaa1429, and ythdf1) were observed in both parental gonads and offspring exposed to BDP. These results reveal that parental exposure to low concentrations of BDP caused offspring vascular disorders by interfering with DNA and RNA methylation, uncovering a unique DNA-RNA modification pattern in the intergenerational transmission of BDP’s developmental toxicity.

show abstract

Section: Results and Discussionsupporting

confidence: 82%

Parental Exposure to Environmentally Relevant Concentrations of Bisphenol-A Bis(diphenyl phosphate) Impairs Vascular Development in Offspring through DNA/RNA Methylation-Dependent Transmission

Wang,

Xu,

Luo

et al. 2023

Environ. Sci. Technol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, TBBPA inhibited the crucial gene expression related to the blood–brain barrier in zebrafish larva head tissue. The analogue BPA exposure could damage blood vessels and the blood–brain barrier and induce brain atherosclerosis, linked to neuroinflammation and nervous system disorders. − Similarly, our previous studies also suggested that cerebrovasculature is a more sensitive target than neuronal effects for flame retardant exposure. , In line with the in vivo study, the in vitro study also demonstrated that TBBPA inhibited cell migration and angiogenic signaling pathways in primary neuroendothelial cells. These data indicate that the neurovascular impairment may be the susceptible target at the early neurodevelopmental stage as well as suggest that the potential contribution of our data to both aquatic toxicity assessment and human health risk assessment.…”

Section: Discussionsupporting

confidence: 57%

“…43−45 Similarly, our previous studies also suggested that cerebrovasculature is a more sensitive target than neuronal effects for flame retardant exposure. 46,47 In line with the in vivo study, the in vitro study also demonstrated that TBBPA inhibited cell migration and angiogenic signaling pathways in primary neuroendothelial cells. These data indicate that the neurovascular impairment may be the susceptible target at the early neurodevelopmental stage as well as suggest that the potential contribution of our data to both aquatic toxicity assessment and human health risk assessment.…”

Section: Discussionmentioning

confidence: 97%

Environmentally Relevant Concentrations of Tetrabromobisphenol A Exposure Impends Neurovascular Formation through Perturbing Mitochondrial Metabolism in Zebrafish Embryos and Human Primary Endothelial Cells

Zeng,

Ma,

Luo

et al. 2024

Environ. Sci. Technol.

Self Cite

View full text Add to dashboard Cite

Tetrabromobisphenol A (TBBPA), the most extensively utilized brominated flame retardant, has raised growing concerns regarding its environmental and health risks. Neurovascular formation is essential for metabolically supporting neuronal networks. However, previous studies primarily concerned the neuronal injuries of TBBPA, its impact on the neurovascularture, and molecular mechanism, which are yet to be elucidated. In this study, 5, 30, 100, 300 μg/L of TBBPA were administered to Tg (fli1a: eGFP) zebrafish larvae at 2−72 h postfertilization (hpf). The findings revealed that TBBPA impaired cerebral and ocular angiogenesis in zebrafish. Metabolomics analysis showed that TBBPA-treated neuroendothelial cells exhibited disruption of the TCA cycle and the Warburg effect pathway. TBBPA induced a significant reduction in glycolysis and mitochondrial ATP production rates, accompanied by mitochondrial fragmentation and an increase in mitochondrial reactive oxygen species (mitoROS) production in neuroendothelial cells. The supplementation of alpha-ketoglutaric acid, a key metabolite of the TCA cycle, mitigated TBBPAinduced mitochondrial damage, reduced mitoROS production, and restored angiogenesis in zebrafish larvae. Our results suggested that TBBPA exposure impeded neurovascular injury via mitochondrial metabolic perturbation mediated by mitoROS signaling, providing novel insight into the neurovascular toxicity and mode of action of TBBPA.

show abstract

“…Overall, the observed specific effects of PBDEs could also be triggered by interactions with receptors on the cell surface. It has been shown that PBDEs interact, for example, with thyroid receptors [33], as well as gamma-aminobutyric acid (GABA) [34], vascular endothelial growth factor (VEGF) [35] or different hormone receptors [36]. Binding to receptors can trigger cascade reactions that can lead to disruptions of the mitochondrial membrane potential and therefore induce production of ROS [36].…”

Section: Discussionmentioning

confidence: 99%

PBDEs Found in House Dust Impact Human Lung Epithelial Cell Homeostasis

Zandona

Jagić

Dvoršćak

et al. 2022

Toxics

View full text Add to dashboard Cite

The toxicity of eight polybrominated diphenyl ethers (PBDEs) congeners detected in environmental and biological samples (BDE-28, -47, -99, -100, -153, -154, -183, and -209) was evaluated on the epithelial lung cells. Exposure to these PBDEs increased membrane disruption and a release of lactate dehydrogenase, accompanied by oxidative stress in cells through the formation of reactive oxygen species (ROS) and a decrease in mitochondrial membrane potential. Interestingly, some of the tested PBDEs increased apoptotic markers as well. For several congeners, the observed toxicity was time dependent, meaning that even smaller concentrations of these compounds will have negative effects over time. Such time-dependent toxicity was also confirmed for cell treatment with a real house dust sample extract. This could be indicative with regard to the constant exposure to a mixture of PBDE congeners through different pathways in the organism and thereby presenting a risk for human health. As such, our findings point to the importance of further studies on the negative effects of PBDEs to understand their mechanism of action in detail.

show abstract

Developmental exposure to BDE-99 hinders cerebrovascular growth and disturbs vascular barrier formation in zebrafish larvae

Cited by 14 publications

References 58 publications

Parental Exposure to Environmentally Relevant Concentrations of Bisphenol-A Bis(diphenyl phosphate) Impairs Vascular Development in Offspring through DNA/RNA Methylation-Dependent Transmission

Parental Exposure to Environmentally Relevant Concentrations of Bisphenol-A Bis(diphenyl phosphate) Impairs Vascular Development in Offspring through DNA/RNA Methylation-Dependent Transmission

Environmentally Relevant Concentrations of Tetrabromobisphenol A Exposure Impends Neurovascular Formation through Perturbing Mitochondrial Metabolism in Zebrafish Embryos and Human Primary Endothelial Cells

PBDEs Found in House Dust Impact Human Lung Epithelial Cell Homeostasis

Contact Info

Product

Resources

About