BDE-47-induced damage prevented by melatonin in grass carp hepatocytes (L8824).

Polybrominated diphenyl ethers (PBDEs) are toxic to organisms with melatonin (MT) providing protection for tissues and cells against these. This study investigates the mechanism of damage of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and the cellular protection of MT on grass carp hepatocytes. Grass carp hepatocytes were exposed to 25 µmol/L BDE-47 and/or 40 µmol/L MT for 24 h before testing. Acridine orange/ethidium bromide (AO/EB) double fluorescence staining results showed that BDE-47 could induce cell apoptosis. The expression levels of the endoplasmic reticulum (ER) stress-related genes ire1, atf4, grp78, perk, and chop were also significantly up-regulated (P < 0.01). The levels of the apoptosis-related genes caspase3, bax, and caspase9 were significantly up-regulated (P < 0.0001), while the level of bcl-2 was significantly down-regulated (P < 0.01). Compared with the BDE-47 group, the BDE-47 + MT group showed reduced levels of ER and apoptosis of hepatocytes, while the expression of the ER stress-related genes ire1, atf4, grp78, perk, and chop and the apoptosis-related genes caspase3, bax, and caspase9 were down-regulated (P < 0.05), and the level of bcl-2 was up-regulated (P < 0.01). In conclusion, BDE-47 can activate ER and apoptosis in grass carp hepatocytes, while MT can reduce these responses.

BDE-99 stimulates generation of aberrant brown/beige adipocytes.

Adipose tissue compromises one of the principal depots where brominated flame retardants (BFR) accumulate in vivo, yet whether BFR disturb thermogenic brown/beige adipocytes is still not referred to date. Herein, effects of BDE-99, a major congener of polybrominated diphenyl ethers (PBDEs) detected in humans, on brown/beige adipocytes were explored for the first time, aiming to provide new knowledge evaluating the obesogenic and metabolic disrupting effects of BFR. Our results firstly demonstrated that exposure to BDE-99 during the lineage commitment period significantly promoted C3H10T1/2 MSCs differentiating into brown/beige adipocytes, evidenced by the increase of brown/beige adipocyte marker UCP1, Cidea as well as mitochondrial membrane potential and basal respiration rate, which was similar to pharmacological PPARγ agonist rosiglitazone. Unexpectedly, the mitochondrial maximal respiration rate of BDE-99 stimulated brown/beige adipocytes was not synchronously enhanced and resulted in a significant reduction of mitochondrial spare respiration capacity (SRC) compared to control or rosiglitazone stimulated adipocytes, indicating a deficient energy-dissipating capacity of BDE-99 stimulated thermogenic adipocytes. Consistently with compromised mitochondrial SRC, lipidomic analysis further revealed that the lipids profile of mitochondria derived from BDE-99 stimulated brown/beige adipocytes were quite different from control or rosiglitazone stimulated cells. In detail, BDE-99 group contains more free fatty acid (FFA) and lyso-PE in mitochondria. In addition to energy metabolism, our results also demonstrated that BDE-99 stimulated brown/beige adipocytes were deficient in endocrine, which secreted more adverse adipokine named resistin, coinciding with comparable beneficial adipokine adiponectin compared with that of rosiglitazone. Taken together, our results showed for the first time that BDE-99 stimulated brown/beige adipocytes were aberrant in energy metabolism and endocrine, which strongly suggests that BDE-99 accumulated in human adipose tissue could interfere with brown/beige adipocytes to contribute to the occurrence of obesity and relevant metabolic disorders.

New Insights into Decabromodiphenyl Ether-Induced Splenic Injury in Chickens: Involvement of ROS-Mediated Endoplasmic Reticulum Stress Pathway Triggering Autophagy and Apoptosis.

Decabromodiphenyl ether (BDE-209) is a widely used brominated flame retardant that can easily detach from materials and enter into feed and foodstuffs, posing a serious risk to human and animal health and food safety of animal origin. However, the immunotoxic effects of BDE-209 on the avian spleen and the exact mechanism of the toxicity remain unknown. Therefore, we established an experimental model of BDE-209-exposed chickens and a positive control model of cyclophosphamide-induced immunosuppression in vivo and treated MDCC-MSB-1 cells and chicken splenic primary lymphocytes with BDE-209 in vitro. The results showed that BDE-209 treatment caused morphological and structural abnormalities in the chicken spleens. Mechanistically, indicators related to oxidative stress, endoplasmic reticulum stress (ERS), autophagy, and apoptosis were significantly altered by BDE-209 exposure in both the spleen and lymphocytes, but the use of the N-acetylcysteine or the 4-phenylbutyric acid significantly reversed these changes. In addition, BDE-209 exposure decreased the spleen antimicrobial peptide and immunoglobulin gene expression. In conclusion, the present research revealed that BDE-209 exposure enhanced lymphocyte autophagy and apoptosis in chicken spleen via the ROS-mediated ERS pathway. This signaling cascade regulatory relationship not only opens up a new avenue for studying BDE-209 immunotoxicity but also provides important insights into preventing BDE-209 hazards to animal health.

Coupling between 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) debromination and methanogenesis in anaerobic soil microcosms.

Polybrominated diphenyl ethers (PBDEs) are persistent pollutants that may undergo microbial-mediated debromination in anoxic environments, where diverse anaerobic microbes such as methanogenic archaea co-exist. However, current understanding of the relations between PBDE pollution and methanogenic process is far from complete. To address this knowledge gap, a series of anaerobic soil microcosms were established. BDE-47 (2, 2', 4, 4'-tetrabromodiphenyl ether) was selected as a model pollutant, and electron donors were supplied to stimulate the activity of anaerobes. Debromination and methane production were monitored during the 12 weeks incubation, while obligate organohalide-respiring bacteria (OHRBs), methanogenic, and the total bacterial communities were examined at week 7 and 12. The results demonstrated slow debromination of BDE-47 in all microcosms, with considerable growth of Dehalococcoides and Dehalogenimonas over the incubation observed in most BDE-47 spiked treatments. In addition, the accumulation of intermediate metabolites positively correlated with the abundance of Dehalogenimonas at week 7, suggesting potential role of these OHRBs in debromination. Methanosarcinaceae were identified as the primary methanogenic archaea, and their abundance were correlated with the production of debrominated metabolites at week 7. Furthermore, it was observed for the first time that BDE-47 considerably enhanced methane production and increased the abundance of mcrA genes, highlighting the potential effects of PBDE pollution on climate change. This might be related to the inhibition of reductive N- and S-transforming microbes, as revealed by the quantitative microbial element cycling (QMEC) analysis. Overall, our findings shed light on the intricate interactions between PBDE and methanogenic processes, and contribute to a better understanding of the environmental fate and ecological implication of PBDE under anaerobic settings.

Disclosing phototransformation mechanisms of decabromodiphenyl ether (BDE-209) in different media by simulated sunlight: Implication by compound-specific stable isotope analysis.

As one of the typical brominated flame retardants, decabromodiphenyl ether (BDE-209) has been widely detected in environment. However, scarce information was available on BDE-209 phototransformation mechanisms in various media. In this study, compound-specific stable isotope analysis was first applied to investigate BDE-209 phototransformation in n-hexane, MeOH:H2O (v:v, 8:2), and simulated seawater by simulated sunlight. BDE-209 transformation followed pseudo-first-order kinetic, with degradation rate in the following of n-hexane (2.66 × 10-3 min-1) > simulated seawater (1.83 × 10-3 min-1) > MeOH:H2O (1.41 × 10-3 min-1). Pronounced carbon isotope fractionation was first observed for BDE-209 phototransformation, with carbon isotope enrichment factors (εC) of -1.01 ± 0.14‰, -1.77 ± 0.26‰, -2.94 ± 0.38‰ in n-hexane, MeOH:H2O and simulated seawater, respectively. Combination analysis of products and stable carbon isotope, debromination with cleavage of C-Br bonds as rate-limiting step was the main mechanism for BDE-209 phototransformation in n-hexane, debromination and hydroxylation with cleavage of C-Br bonds as rate-limiting steps in MeOH:H2O, and debromination, hydroxylation and chlorination in simulated seawater. This present study confirmed that stable carbon isotope analysis was a robust method to discovery the underlying phototransformation mechanisms of BDE-209 in various solutions.

Modified nano zero-valent iron coupling microorganisms to degrade BDE-209: Degradation pathways and microbial responses.

Polybrominated diphenyl ethers (PBDEs) in soil and groundwater have garnered considerable attention owing to the significant bioaccumulation potential and toxicity. Currently, the coupling treatment method of nano zero-valent iron (nZVI) with dehalogenation microorganisms is a research hotspot in the field of PBDE degradation. In this study, various systems were established within anaerobic environments, including the nZVI-only system, microorganism-only system, and the nZVI + microorganisms system. The aim was to investigate the degradation pathway of BDE-209 and elucidate the degradation mechanism within the coupled system. The results indicated that the degradation efficiency of the coupled system was better than that of the nZVI-only or microorganism-only system. Two modified nZVI (carboxymethyl cellulose and polyacrylamide) were prepared to improve the coupling degradation efficiency. CMC-nZVI showed the highest stability, and the coupled system consisting of microorganisms and CMC-nZVI showed the best degradation effect among all of the systems in this study, reaching 89.53% within 30 days. Furthermore, 22 intermediate products were detected in the coupling systems. Notably, changing the inoculation time did not significantly improve the degradation effect. The expression changes of the two reductive dehalogenase genes, e.g. TceA and Vcr, reflected the stress response and self-recovery ability of the dehalogenating bacteria, indicating such genes can be used as biomarker for evaluating the degradation performance of the coupling system. These findings provide a better understanding about the mechanism of coupling debromination process and the direction for the optimization and on-site repair of coupled systems.

Varying temporal trends in the levels of six groups of legacy persistent organic pollutants (POPs) in liver of three gadoid species from the North Sea.

From 2005 to 2019, three gadoid species, Atlantic cod (Gadus morhua), haddock (Melanogrammus aeglefinus) and saithe (Pollachius virens), were sampled approximately every third year in the northeastern part of the North Sea. Liver samples were analyzed to investigate levels and temporal trends of six groups of persistent organic pollutants (POPs): polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and its degradation products, hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), trans-nonachlor (TNC), and polybrominated diphenyl ethers (PBDEs). Some of the highest average concentrations were found in cod, the levels otherwise being similar between the three species and mostly below established threshold values. The levels of all the contaminants except HCB and TNC were higher than previously reported for cod and haddock in the Barents Sea. Significantly decreasing levels were found for Σ7PCBs, ΣDDTs, ΣHCHs and Σ15PBDEs in all three species, and for TNC in haddock and saithe, while there was no significant trend for TNC in cod. HCB levels increased significantly in cod and haddock and showed only a minor decrease in saithe. The observed time trends of legacy POPs demonstrate the persistence of some of the studied pollutants despite efforts to eliminate them from the marine environment.

Metabolomic insights into neurological effects of BDE-47 exposure in the sea cucumber Apostichopus japonicus.

The persistent organic pollutant 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), a prevalent congener among polybrominated diphenyl ethers (PBDEs), exhibits potent bioaccumulation and toxicity. Despite extensive research into the adverse effects of BDE-47, its neurotoxicity in sea cucumbers remains unexplored. Given the crucial role of the sea cucumber's nervous system in survival and adaptation, evaluating the impacts of BDE-47 is vital for sustainable aquaculture and consumption. In this study, we employed ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Triple-TOF-MS) to analyze metabolomic changes in neuro-related tissues of Apostichopus japonicus exposed to low (0.1 µg/L), medium (1.0 µg/L), and high (10.0 µg/L) BDE-47 concentrations. We identified significantly changed metabolites in each exposure group (87 in low, 79 in medium, and 102 in high), affecting a variety of physiological processes such as steroid hormone balance, nucleotide metabolism, energy metabolism, neurotransmitter levels, and neuroprotection. In addition, we identified concentration-dependent, common, and some other metabolic responses in the neuro-related tissues. Our findings reveal critical insights into the neurotoxic effects of BDE-47 in sea cucumbers and contribute to risk assessment related to BDE-47 exposure in the sea cucumber industry, paving the way for future neurotoxicological research in invertebrates.

BDE-209-induced genotoxicity, intestinal damage and intestinal microbiota dysbiosis in zebrafish (Danio Rerio).

The environmental presence of polybrominated diphenyl ethers (PBDEs) is ubiquitous due to their wide use as brominated flame retardants in industrial products. As a common congener of PBDEs, decabromodiphenyl ether (BDE-209) can pose a health risk to animals as well as humans. However, to date, few studies have explored BDE-209's toxic effects on the intestinal tract, and its relevant mechanism of toxicity has not been elucidated. In this study, adult male zebrafish were exposed to BDE-209 at 6 µg/L, 60 µg/L and 600 µg/L for 28 days, and intestinal tissue and microbial samples were collected for analysis to reveal the underlying toxic mechanisms. Transcriptome sequencing results demonstrated a dose-dependent pattern of substantial gene differential expression in the group exposed to BDE-209, and the differentially expressed genes were mainly concentrated in pathways related to protein synthesis and processing, redox reaction, and steroid and lipid metabolism. In addition, BDE-209 exposure caused damage to intestinal structure and barrier function, and promoted intestinal oxidative stress, inflammatory response, apoptosis and steroid and lipid metabolism disorders. Mechanistically, BDE-209 induced intestinal inflammation by increasing the levels of TNF-α and IL-1ß and activating the NFκB signaling pathway, and might induce apoptosis through the p53-Bax/Bcl2-Caspase3 pathway. BDE-209 also significantly inhibited the gene expression of rate-limiting enzymes such as Sqle and 3ßhsd (p < 0.05) to inhibit cholesterol synthesis. In addition, BDE-209 induced lipid metabolism disorders through the mTOR/PPARγ/RXRα pathway. 16S rRNA sequencing results showed that BDE-209 stress reduced the richness and diversity of intestinal microbiota, and reduced the abundance of probiotics (e.g., Bifidobacterium and Faecalibacterium). Overall, the results of this study help to clarify the intestinal response mechanism of BDE-209 exposure, and provide a basis for evaluating the health risks of BDE-209 in animals.

Photosynthetic response mechanism to polybrominated diphenyl ether exposure in Chlorella pyrenoidosa.

Polybrominated diphenyl ether (PBDE) contamination is common in aquatic environments and can severely damage aquatic organisms. However, there is a lack of information on the response and self-adaptation mechanisms of these organisms. Chlorella pyrenoidosa was treated with 2,2',4,4'-tetrabromodiphenyl ether (BDE47), causing significant growth inhibition, pigment reduction, oxidative stress, and chloroplast atrophy. Photosynthetic damage contributed to inhibition, as indicated by Fv/Fm, Chl a fluorescence induction, photosynthetic oxygen evolution activity, and photosystem subunit stoichiometry. Here, Chl a fluorescence induction and quinone electron acceptor (QA-) reoxidation kinetics showed that the PSII donor and acceptor sides were insensitive to BDE47. Quantitative analyses of D1 and PsaD proteins illustrated that PSII and PSI complexes were the main primary targets of photosynthesis inhibition by BDE47. Significant modulation of PSII complex might have been caused by the potential binding of BDE47 on D1 protein, and molecular docking was performed to investigate this. Increased activation of antioxidant defense systems and photosystem repair as a function of exposure time indicated a positive resistance to BDE47. After a 5-day exposure, 23 % of BDE47 was metabolized. Our findings suggest that C. pyrenoidosa has potential as a bioremediator for wastewater-borne PBDEs and can improve our understanding of ecological risks to microalgae.

2,2',4,4'-tetrabromodiphenyl ether causes depigmentation in zebrafish larvae via a light-mediated pathway.

Polybrominated diphenyl ethers (PBDEs) are organic pollutants widely detected in various environmental media due to their high persistence and bioaccumulation. PBDE-induced visual impairment and neurotoxicity were previously demonstrated using zebrafish (Danio rerio) models, and recent research reported the phenotypic depigmentation effect of PBDEs at high concentrations on zebrafish, but whether those effects are still present at environment-relevant levels is still unclear. Herein, we performed both phenotypic examination and mechanism investigation in zebrafish embryos (48 hpf) and larvae (5 dpf) about their pigmentation status when exposing to PBDE congener BDE-47 (2,2',4,4'-tetrabrominated diphenyl ether) at levels from 0.25 to 25 µg/L. Results showed that low-level BDE-47 can restrain the relative melanin abundance of zebrafish larvae to 70.47% (p < 0.05) and 61.54% (p < 0.01) respectively under 2.5 and 25 µg/L BDE-47 compared with control, and the thickness of retinal pigment epithelium (RPE) remarkably reduced from 571.4 nm to 350.3 nm (p < 0.001) under 25 µg/L BDE-47 exposure. We also observed disrupted expressions of melanin synthesis genes and disorganized mitfa differentiation patterns based on Tg(mifta:EGFP), as well as visual impairment resulting from thinner RPE. Considering both processes of visual development and melanin synthesis are highly sensitive to ambient light conditions, we prolonged the light regime of maintaining zebrafish larvae from 14 hours light versus 10 hours dark (14L:10D) to 18 hours light versus 6 hours dark (18L:6D). Lengthening photoperiod successfully rescued the fluorescent level of mitfa in zebrafish epidermis and most gene expressions associated with melanin synthesis under 25 µg/L BDE-47 exposure to the normal level. In conclusion, our work reported the effects of low-level PBDEs on melanin production using zebrafish embryos and larvae, and identified the potential role of a light-mediated pathway in the neurotoxic mechanism of PBDEs.

Biomagnification and elimination effects of persistent organic pollutants in a typical wetland food web from South China.

This study investigated the quantitative sources of persistent organic pollutants (POPs), their biomagnification factors, and their effect on POP biomagnification in a typical waterbird (common kingfisher, Alcedo atthis) food web in South China. The median concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in kingfishers were 32,500 ng/g lw and 130 ng/g lw, respectively. The congener profiles of PBDEs and PCBs showed significant temporal changes because of the restriction time points and biomagnification potential of different contaminants. The concentrations of most bioaccumulative POPs, such as CBs 138 and 180 and BDEs 153 and 154, decreased at lower rates than those of other POPs. Pelagic fish (metzia lineata) and benthic fish (common carp) were the primary prey of kingfishers, as indicated by quantitative fatty acid signature analysis (QFASA) results. Pelagic and benthic prey species were the primary sources of low and high hydrophobic contaminants for kingfishers, respectively. Biomagnification factors (BMFs) and trophic magnification factors (TMFs) had parabolic relationships with log KOW, with peak values of approximately 7. Significant negative correlations were found between the whole-body elimination rates of POPs in waterbirds and the log-transformed TMFs and BMFs, indicating that the strong metabolism of waterbirds could potentially affect POP biomagnification.

Proteomic analyses of primary human villous trophoblasts exposed to flame retardant BDE-47 using SWATH-MS.

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants and recognized developmental toxicants that are detectable in placental tissues. Higher levels of in utero PBDE exposure have been associated with an increased risk of adverse birth outcomes. During pregnancy, cytotrophoblasts (CTBs) from the placenta play critical roles in the formation of the maternal-fetal interface via uterine invasion and vascular remodeling. The differentiation of these cells towards an invasive phenotype is crucial for proper placental development. We previously have shown that BDE-47 can impact CTB viability and hinder the ability of these cells to migrate and invade. To expand on potential toxicological mechanisms, we utilized quantitative proteomic approaches to identify changes in the global proteome of mid-gestation primary human CTBs after exposure to BDE-47. Using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), we identified 3024 proteins in our CTB model of differentiation/invasion. Over 200 proteins were impacted as a function of BDE-47 exposure (1 µM and 5 µM) across the treatment period (15, 24, and 39 h). The differentially expressed molecules displayed time- and concentration-dependent changes in expression and were enriched in pathways associated with aggregatory and adhesive processes. Network analysis identified CYFIP1, a molecule previously unexplored in a placental context, to be dysregulated at BDE-47 concentrations previously seen to impact CTB migration/invasion. Our SWATH-MS dataset thus demonstrates BDE-47 impacts the global proteome of differentiating CTBs and serves as a valuable resource for further understanding of the relationship between environmental chemical exposures and placental development and function. AVAILABILITY OF DATA AND MATERIAL: Raw chromatograms are deposited on the MassIVE proteomic database (https://massive.ucsd.edu) under accession number MSV000087870. Normalized relative abundances are also available as Table S1.

Curcumin alleviates spleen immunotoxicity induced by decabrominated diphenyl ethers (BDE-209) by improving immune function and inhibiting inflammation and apoptosis in broilers.

This study was conducted to assess the mitigating effects of curcumin (Cur) on immunotoxicity in the spleen of broilers induced by the polybrominated diphenyl ether BDE-209. Eighty one-day-old broilers were allocated to the following four groups: control group, BDE-209 (0.4 g/kg) group, BDE-209 (0.4 g/kg) + Cur (0.3 mg/kg) group, and Cur (0.3 mg/kg) group. Growth performance, immunological function, inflammation, and apoptosis were assessed after 42 days of treatment. The findings demonstrate that firstly, Cur restored spleen damage caused by BDE-209 by increasing body weight, decreasing feed-to-gain ratio, correcting the spleen index, and improving the histopathological structure of the spleen. Secondly, Cur relieved BDE-209-induced immunosuppression by increasing the levels of the immunoglobulins IgG, IgM, and IgA in the serum, as well as the levels of white blood cells and lymphocytes. The levels at which GATA binding protein 3, T-box expressed in T cells, interferon-γ, and interleukin (IL)- 4 are expressed were controlled. The ratio of T helper (Th) type 1 (Th1) to Th2 cells in the spleen of broilers was also controlled. Thirdly, Cur reduced the expression of Toll like receptor (TLR) 2, TLR4, nuclear factor (NF)-κB, IL-8, IL-6, and IL-1ß, which alleviated BDE-209-induced inflammation in broilers. Cur reduced BDE-209-induced apoptosis by increasing the expression of the bcl-2 protein, decreasing the expression of cleaved caspase-3 and bax proteins, decreasing the bax/bcl-2 protein ratio, and decreasing the mean optical density of TUNEL. These results suggest that Cur protects broiler spleens from BDE-209-induced immunotoxicity via modulating humoral immunity, the equilibrium between Th1 and Th2 cells, the TLRs/NF-κB inflammatory pathway, and the apoptotic pathway.

MiR-24-3p/Dio3 axis is essential for BDE47 to induce local thyroid hormone disorder and neurotoxicity.

BDE47 (2,2,4,4-tetrabromodiphenyl ether) is a member of the most important congeners of polybrominated diphenyl ethers (PBDEs) and has been identified as a developmental, reproductive and nervous system toxicant and endocrine system disruptor due to its frequent detection in human tissue and environmental samples. Our preliminary work suggested that high- and low-level of bromodiphenyl ethers have different effects on neuronal cells with differential targets of actions on neural tissues. In this study, we presented the underlying mechanism of BDE47 neurotoxicity from the perspective of thyroid hormone (TH) metabolism using in vitro model of human SK-N-AS neuronal cells. BDE47 could induce local TH metabolism disorder in neuronal cells by inhibiting the expression of the main enzyme, human type III iodothyronine deiodinase (Dio3). Further elucidation revealed that BDE47 effectively up-regulating miR-24-3p, which binds to the 3'-UTR of Dio3 and inhibits its expression. In addition, BDE47 could also inhibit the deiodinase activity of Dio3. Collectively, our study demonstrates the molecular mechanism of BDE47 regulating Dio3-induced TH metabolism disorder through inducing miR-24-3p, providing new clues for the role of miRNAs in neurodevelopmental toxicity mediated by environmental pollutants.

The crosstalk effects of polybrominated diphenyl ethers on the retinoic acid and thyroid hormone signaling pathway.

The toxicological and pathological influences of polybrominated diphenyl ethers (PBDEs) on the animal central nervous system have attracted worldwide attention. However, their mechanism of action has not been completely elucidated. Given that retinoic acid (RA) and thyroid hormone (TH) signaling pathway are closely related to neurodevelopment, the crosstalk between the two signaling pathways at the levels of metabolite conversion, gene expression and ligand-receptor interaction after exposure to two representative PBDE congeners (BDE-47 and BDE-209) using zebrafish larvae, dual reporter gene assay, and docking simulation was studied. Our results clarified that BDE-47 could disrupt the transport and metabolism of retinoids, induce changes in expression of key genes, bind with the seven nuclear receptors, and activate RA signaling pathway. BDE-47 exhibited more effects on the indicators of the two signaling pathways than BDE-209. Furthermore, BDE-47 may disrupt TH signaling pathway by disrupting RA signaling pathway, indicating that RA signal is priorly influenced than TH signal. This work offered a new perspective to elucidate TH signal disruption mechanism induced by PBDEs from RA signaling pathway, which is of great significance to elucidate the health effects of PBDEs.

Autophagy: A newly discovered protective mechanism in the marine rotifer Brachionus plicatilis in response to BDE-47 exposure.

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is a persistent organic pollutant that spreads widely in the marine environment. Our previous studies found that it had adverse effects on the marine rotifer Brachionus plicatilis and caused a series of stress responses. The present study was performed to verify the occurrence of autophagy and explore its role in B. plicatilis' coping with BDE-47 exposure. Rotifers were exposed to 0.05, 0.2, 0.8, and 3.2 mg/L BDE-47 for 24 h, respectively. Detections of the autophagy marker protein LC3 by western blot and autophagosomes by MDC staining demonstrated the occurrence of autophagy. The levels of autophagy were significantly increased in BDE-47-treated groups with a peak in 0.8 mg/L group. A series of indicators responded to BDE-47 exposure, including reactive oxygen species (ROS), GSH/GSSG ratio, superoxide dismutase (SOD) activity, and malonaldehyde (MDA), collectively indicating the occurrence of oxidative stress. The potential interplay between autophagy and oxidative stress in B. plicatilis was explored in the 0.8 mg/L group through a series of additions. The ROS level was significantly decreased by the addition of the ROS generation inhibitor diphenyleneiodonium chloride, to a level even lower than that in the blank control, and concomitantly, autophagosome was almost undetectable, indicating that a certain level of ROS was essential for the occurrence of autophagy. Autophagy was weakened by the addition of the autophagy inhibitor 3-methyladenine coincident with the great elevation of ROS, indicating that activated autophagy contributed to reducing the ROS level. Additional proof of this relation was obtained from the direct opposite effects of the autophagy inhibitor bafilomycin A1 and the autophagy activator rapamycin: the former increased the MDA content significantly, whereas the latter decreased it significantly. The combined results suggested that autophagy alleviated oxidative stress and might be a newly discovered protective mechanism in B. plicatilis coping with BDE-47 exposure.

BDE-209 disrupted the blood-testis barrier integrity by inhibiting estrogen receptor α signaling pathway in Sprague-Dawley rats.

Deca brominated diphenyl ether (BDE-209) is a widely used flame retardant with endocrine-disrupting activity which reportedly caused sperm quality decline and damaged blood-testis barrier (BTB). However, whether BDE-209 exposure led to BTB integrity dysfunction through affecting microtubule cytoskeletal organization and junctions was not well-elucidated. This study aimed to investigate the role of estrogen receptor α (ERα) in BDE-209-mediated perturbation of BTB integrity. Male rats and primary culture Sertoli cells were co-treated with BDE-209 and propylpyrazoletriol (PPT). The data demonstrated that BDE-209 impaired BTB integrity by reducing crucial tight junction-related proteins with ZO-1 and Occludin. Furthermore, the data suggested that BDE-209 diminished the apical ectoplasmic specialization markers with Eps8 and Formin1. In addition, BDE-209 damaged BTB ultrastructure including tight junctions and ectoplasmic specialization structures with broken tight junctions and the absence of actin microfilaments. Further experiments revealed that ERα was triggered in BDE-209-treated Sertoli cells. Unexpectedly, we found that PPT rescued BDE-209-mediated disruption of BTB integrity including tight junction and apical ectoplasmic specialization by activating ERα in Sertoli cells. Taken together, these findings indicated that intratesticular BDE-209 exposure perturbed BTB integrity and destroyed BTB structure by blocking ERα pathway. Our findings provide a new therapeutic target for male reproductive dysfunction.

Comparative evaluation and prioritization of key influences on biodegradation of 2,2',4,4'-tetrabrominated diphenyl ether by bacterial isolate B. xenovorans LB400.

Polybrominated diphenyl ethers (PBDEs) are a class of persistent organic pollutants being widely distributed and harmful to human health and wildlife, and the development of sustainable rehabilitation strategies including microbial degradation is of great concern. Although the increasing number of bacteria, especially the broad-spectrum and potent aerobes have been isolated for the efficient removal of PBDEs, the external influences and the corresponding influential mechanism on biodegradation are not fully understood yet. Given the wide-spectrum biodegradability of aerobic bacterial isolate, B. xenovorans LB400 for PBDEs, the dual impacts of many pivotal factors including pH, temperature, presence of dissolved organic matter (DOM) and cadmium ion etc. were comprehensively revealed on biodegradation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). Due to the structural resemblance and stimulation of specific enzyme activity in bacteria, the biphenyl as substrates showed the greater capacity than non-aromatic compounds in improving biodegradation. The individual adaptation to neutrality and cultivation at about 30 °C was beneficial for biodegradation since the bacterial cellular viability and enzyme activity was mostly preserved. Although it was possibly good for the induction of hormesis and favorable to enhance the permeability or bioavailability of pollutant, the exceeding increase of Cd2+ or DOM may not give the profitable increase of biodegradation yet for the detrimental effect. For biodegradation, the mechanistic relationship that took account of the integrative correlation with the influential factors was artfully developed using partial least square (PLS) regression technique. Relative to the most significant influence of culture time and initial concentration of BDE-47, the larger relevance of other factors primarily marked as pH and DOM was consecutively shown after the quantitative prioritization. This may not only help understand the influential mechanism but provide a prioritizing regulation strategy for biodegradation of BDE-47. The PLS-derived relationship was validated with the certain predictability in biodegradation, and could be used as an alternative to accelerate a priori evaluation of suitability or improve the feasibility of such bacteria in remediation of PBDEs in the environment.

Acetyltransferase OsACE2 acts as a regulator to reduce the environmental risk of oxyfluorfen to rice production.

The constant use of the pesticide oxyfluorfen (OFF) in farmland contaminates the soil, posing threats to crop growth and human health. To avoid the contamination of food crops with OFF, it is critically important to understand its absorption and degradation mechanisms. In this study, we characterized a new functional locus encoding an acetyltransferase (OsACE2) that can facilitate OFF degradation in rice. OsACE2 was drastically induced by OFF at 0.04-0.2 mg L-1 for 6 days and the rice growth was significantly inhibited. To demonstrate the regulatory role of OsACE2 in resistance to OFF toxicity, we generated OsACE2 overexpression (OE) and knockout mutant using genetic transformation and gene-editing technologies (CRISPR/Cas9). The OE plants grown in the hydroponic medium showed improved growth (plant elongation and biomass), increased chlorophyll content, and reduced OFF-induced oxidative stress. The OsACE2-improved growth phenotypes of rice were attributed to the significantly lower OFF accumulation in OE plants. Conversely, knocking out OsACE2 resulted in compromised growth phenotypes compared to the wild-type (WT). Using LC-LTQ-HRMS/MS, five mono-metabolites and eleven conjugates of OFF were characterized through various canonical pathways, such as hydrolysis, oxidation, reduction, glycosylation, acetylation, malonylation, and interaction with amino acids. These metabolites increased in the OE plants, and five acetylated conjugates were reported for the first time. Collectively, OsACE2 plays a primary role in catabolizing OFF residues in rice through multiple degradation pathways and reducing OFF in its growth environment.