Exposure to BDE-47 causes female infertility risk and induces oxidative stress and lipotoxicity-mediated ovarian hormone secretion disruption in mice

Shaoyong, Weike; Liu, Yalin; Xu, Bocheng; Pan, Bo; Xianmi, Xinuer; Wang, Yizhen; Jin, Mingliang

doi:10.1016/j.scitotenv.2022.156885

Cited by 12 publications

(8 citation statements)

References 45 publications

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“…Secondly, the Xanthine Oxidase (XOD)-catalyzed production of H 2 O 2 and O 2 − has been shown to be the main source of excess ROS in cells under BDE-47 stress [20]. Similarly, the activation of XOD in purine metabolism promoted ROS overproduction of B. plicatilis in this study, while the collapse of the antioxidant system and the oxidative damage caused by BDE-47-induced excessive ROS production has been widely reported [6,[21][22][23].…”

Section: Discussionsupporting

confidence: 50%

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Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer Brachionus plicatilis

Cao

Wang

You

et al. 2023

IJMS

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This present study was conducted to provide evidence and an explanation for the apoptosis that occurs in the marine rotifer Brachionus plicatilis when facing 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) stress. Metabolomics analysis showed that aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, and arginine biosynthesis were the top three sensitive pathways to BDE-47 exposure, which resulted in the reduction in the amino acid pool level. Pyrimidine metabolism and purine metabolism pathways were also significantly influenced, and the purine and pyrimidine content were obviously reduced in the low (0.02 mg/L) and middle (0.1 mg/L) concentration groups while increased in the high (0.5 mg/L) concentration group, evidencing the disorder of nucleotide synthesis and decomposition in B. plicatilis. The biochemical detection of the key enzymes in purine metabolism and pyrimidine metabolism showed the downregulation of Glutamine Synthetase (GS) protein expression and the elevation of Xanthine Oxidase (XOD) activity, which suggested the impaired DNA repair and ROS overproduction. The content of DNA damage biomarker (8-OHdG) increased in treatment groups, and the p53 signaling pathway was found to be activated, as indicated by the elevation of the p53 protein expression and Bax/Bcl-2 ratio. The ROS scavenger (N-acetyl-L-cysteine, NAC) addition effectively alleviated not only ROS overproduction but also DNA damage as well as the activation of apoptosis. The combined results backed up the speculation that purine metabolism and pyrimidine metabolism alteration play a pivotal role in BDE-47-induced ROS overproduction and DNA damage, and the consequent activation of the p53 signaling pathway led to the observed apoptosis in B. plicatilis.

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Section: Discussionsupporting

confidence: 50%

“…Similarly, the activation of XOD in purine metabolism promoted ROS overproduction of B . plicatilis in this study, while the collapse of the antioxidant system and the oxidative damage caused by BDE-47-induced excessive ROS production has been widely reported [ 6 , 21 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 67%

Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer Brachionus plicatilis

Cao

Wang

You

et al. 2023

IJMS

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“…Proteomics analysis based on 2D gel electrophoresis detected 64 differentially regulated proteins participating in many cell processes, including apoptosis (31.3%), proliferation (17.2%), oxidative stress (17.2%) and mitochondrial damage, cell respiration and the generation of ROS. Fifteen differentially expressed proteins (23.4%) were located in the mitochondria, 13 (20.3%) in the cytoskeleton, and 6 (9.4%) were in the endoplasmic reticulum. – In female C57BL/six mice exposed by gavage to 0, 10, 50 or 100 mg BDE‐47 /kg bw per day for 5 weeks, ovarian lipid deposition (increased lipid droplets and free fatty acid levels) and ovarian hormone changes accompanied by oxidative stress (increase in ROS and MDA concentrations) were observed, as well as downregulation of hormone biosynthesis‐related proteins (Shaoyong et al., 2022). BDE‐47 exposure reduced the serum levels of oestradiol and progesterone and thereby damaged the oestrus cycle and female fertility.…”

Section: Assessmentmentioning

confidence: 99%

“…In female C57BL/six mice exposed by gavage to 0, 10, 50 or 100 mg BDE‐47 /kg bw per day for 5 weeks, ovarian lipid deposition (increased lipid droplets and free fatty acid levels) and ovarian hormone changes accompanied by oxidative stress (increase in ROS and MDA concentrations) were observed, as well as downregulation of hormone biosynthesis‐related proteins (Shaoyong et al., 2022 ). BDE‐47 exposure reduced the serum levels of oestradiol and progesterone and thereby damaged the oestrus cycle and female fertility.…”

Section: Assessmentmentioning

confidence: 99%

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food

Schrenk,

Bignami,

Bodin

et al. 2024

EFS2

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The European Commission asked EFSA to update its 2011 risk assessment on polybrominated diphenyl ethers (PBDEs) in food, focusing on 10 congeners: BDE‐28, ‐47, ‐49, ‐99, ‐100, ‐138, ‐153, ‐154, ‐183 and ‑209. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour and reproductive/developmental effects are the critical effects in rodent studies. For four congeners (BDE‐47, ‐99, ‐153, ‐209) the Panel derived Reference Points, i.e. benchmark doses and corresponding lower 95% confidence limits (BMDLs), for endpoint‐specific benchmark responses. Since repeated exposure to PBDEs results in accumulation of these chemicals in the body, the Panel estimated the body burden at the BMDL in rodents, and the chronic intake that would lead to the same body burden in humans. For the remaining six congeners no studies were available to identify Reference Points. The Panel concluded that there is scientific basis for inclusion of all 10 congeners in a common assessment group and performed a combined risk assessment. The Panel concluded that the combined margin of exposure (MOET) approach was the most appropriate risk metric and applied a tiered approach to the risk characterisation. Over 84,000 analytical results for the 10 congeners in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary Lower Bound exposure to PBDEs were meat and meat products and fish and seafood. Taking into account the uncertainties affecting the assessment, the Panel concluded that it is likely that current dietary exposure to PBDEs in the European population raises a health concern.

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“…[ 14 ] For example, 2,2,4,4‐tetrabromodiphenyl ether inhibits the secretion of ovarian hormones in mice through oxidative stress‐mediated autophagy and apoptosis of the mitochondrial pathway. [ 15 ] Endocrine hormones are the primary factors regulating ovarian development, and abnormal hormone secretion is associated with ovarian diseases. [ 16 ] Zearalenone has estrogen‐like effects that cause severe reproductive toxicity in humans and animals.…”

Section: Introductionmentioning

confidence: 99%

Effects of Alginic Acid on the Porcine Granulosa Cells and Maturation of Porcine Oocytes

Wang,

Li,

Yuan

et al. 2023

Molecular Nutrition Food Res

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ScopeAlginic acid (AA) from brown algae is a marine organic compound. There is extensive use of AA in the food industry and healthcare, suggesting a high probability of AA exposure. The present study investigates the effects of AA on porcine ovarian granulosa cells (GCs) and oocytes to explore its mechanism in female reproduction because of its adverse effects on reproduction.Methods and resultsThe study adds 20 µM AA to the porcine primary ovarian GCs medium and porcine oocyte in vitro maturation (IVM) medium. Estrogen and progesterone levels are downregulated in GCs. Reactive oxygen species are excessive, and the antioxidant capacity declines. Then mitochondria‐mediated apoptosis pathway is involved in GCs apoptosis. In addition, scores of autophagosomes are found in the experimental cells. Furthermore, AA significantly inhibits the proliferation of GCs around cumulus‐oocyte complexes (COCs) accompanied by abnormal spindle assembly, chromosome arrangement disorder, and aberrant cortical granules distribution in oocytes, leading to a decreased oocyte maturation rate.ConclusionThese findings suggest that 20 µM AA is toxic to sow reproduction by interfering with estrogen production, oxidative stress, mitochondria‐mediated apoptosis, autophagy in GCs of sows, and oocyte maturation.

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Exposure to BDE-47 causes female infertility risk and induces oxidative stress and lipotoxicity-mediated ovarian hormone secretion disruption in mice

Cited by 12 publications

References 45 publications

Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer Brachionus plicatilis

Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer Brachionus plicatilis

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food

Effects of Alginic Acid on the Porcine Granulosa Cells and Maturation of Porcine Oocytes

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