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Exogenous melatonin protects preimplantation embryo development from decabromodiphenyl ethane-induced circadian rhythm disorder and endogenous melatonin reduction
2022
Shi, Feifei | Qiu, Jinyu | Zhang, Shaozhi | Zhao, Xin | Feng, Daofu | Feng, Xizeng
Decabromodiphenyl ethane (DBDPE) is a novel flame retardant that is widely used in plastics, electronic products, building materials and textiles. Our previous studies have revealed the oocyte toxicity of DBDPE, but the effect of DBDPE on preimplantation embryo development has not been reported. Here, we investigated whether and how DBDPE exposure affects preimplantation embryo development. Adult female mice were orally exposed to DBDPE (0, 5, 50, 500 μg/kg bw/day) for 14 days. First, we found that after DBDPE exposure, mice showed obvious circadian rhythm disorder. Moreover, the development of preimplantation embryos was inhibited in DBDPE-exposed mice after pregnancy. Then, we further explored and revealed that DBDPE exposure reduced the endogenous melatonin (MLT) level during pregnancy, thereby inhibiting the development of preimplantation embryos. Furthermore, we discovered that exogenous MLT supplementation (15 mg/kg bw/day) rescued the inhibition of preimplantation embryo development induced by DBDPE, and a mechanistic study demonstrated that exogenous MLT inhibited the overexpression of ROS and DNA methylation at the 5-position of cytosine (5-mC) in DBDPE-exposed preimplantation embryos. Simultaneously, MLT ameliorated the DBDPE-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential (MMP), ATP, and Trp1 expression. Additionally, MLT restored DBDPE-induced changes in zona pellucida (ZP) hardness and trophectoderm (TE) cortical tension. Finally, the protective effect of MLT on embryos ameliorated the adverse reproductive outcomes (dead fetus, fetus with abnormal liver, fetal weight loss) induced by DBDPE. Collectively, DBDPE induced preimplantation embryo damage leading to adverse reproductive outcomes, and MLT has emerged as a potential tool to rescue adverse reproductive outcomes induced by DBDPE.
اظهر المزيد [+] اقل [-]Environmentally relevant exposure to TBBPA and its analogues may not drastically affect human early cardiac development
2022
Zhao, Miaomiao | Yin, Nuoya | Yang, Renjun | Li, Shichang | Zhang, Shuxian | Faiola, Francesco
Tetrabromobisphenol A (TBBPA) and its substitutes and derivatives have been widely used as halogenated flame retardants (HFRs), in the past few decades. As a consequence, these compounds are frequently detected in the environment, as well as human bodily fluids, especially umbilical cord blood and breast milk. This has raised awareness of their potential risks to fetuses and infants. In this study, we employed human embryonic stem cell differentiation models to assess the potential developmental toxicity of six TBBPA-like compounds, at human relevant nanomolar concentrations. To mimic early embryonic development, we utilized embryoid body-based 3D differentiation in presence of the six HFRs. Transcriptomics data showed that HFR exposure over 16 days of differentiation only interfered with the expression of a few genes, indicating those six HFRs may not have specific tissue/organ targets during embryonic development. Nevertheless, further analyses revealed that some cardiac-related genes were dysregulated. Since the heart is also the first organ to develop, we employed a cardiac differentiation model to analyze the six HFRs’ potential developmental toxicity in more depth. Overall, HFRs of interest did not significantly disturb the canonical WNT pathway, which is an essential signal transduction pathway for cardiac development. In addition, the six HFRs showed only mild changes in gene expression levels for cardiomyocyte markers, such as NKX2.5, MYH7, and MYL4, as well as a significant down-regulation of some but not all the epicardial and smooth muscle cell markers selected. Taken together, our results show that the six studied HFRs, at human relevant concentrations, may impose negligible effects on embryogenesis and heart development. Nevertheless, higher exposure doses might affect the early stages of heart development.
اظهر المزيد [+] اقل [-]Effect of flupyradifurone on zebrafish embryonic development
2021
Zhong, Keyuan | Meng, Yunlong | Wu, Juan | Wei, You | Huang, Yong | Ma, Jinze | Lu, Huiqiang
Evaluation of the toxicity of pesticide residues on non-target organisms in the ecosystem is an important part of pesticide environmental risk assessment. Flupyradifurone is a new type of butenolide insecticide produced by Bayer, who claims it to be “low toxic” to non-target organisms in the environment. However, there is little evidence in the literature to show how flupyradifurone affects aquatic organism development. In the current study, zebrafish embryos were treated with 0.1, 0.15, and 0.2 mg/mL of flupyradifurone within 6.0–72 h past fertilization (hpf). We found that the half-lethal concentration (LC₅₀) of flupyradifurone for zebrafish embryos at 96 hpf was 0.21 mg/mL. Flupyradifurone decreases the heart rate, survival rate, and body length of zebrafish embryos. The flupyradifurone treatment also led to the failure of heart looping, and pericardial edema. Moreover, flupyradifurone increased the level of reactive oxygen species (ROS) and decreased the enzymatic catalysis of catalase (CAT) and superoxide dismutase (SOD). Alterations were induced in the transcription of apoptosis-related genes (bcl-2, bax, bax/bcl-2, p53 and caspase-9) and the heart development-related genes (gata4, myh6, nkx2.5, nppa, tbx2b, tbx5 and vmhc). In the current study, new evidences have been provided regarding the toxic effects of flupyradifurone and the risk of its residues in agricultural products and the environment.
اظهر المزيد [+] اقل [-]Xenopus in revealing developmental toxicity and modeling human diseases
2021
Gao, Juanmei | Shen, Wanhua
The Xenopus model offers many advantages for investigation of the molecular, cellular, and behavioral mechanisms underlying embryo development. Moreover, Xenopus oocytes and embryos have been extensively used to study developmental toxicity and human diseases in response to various environmental chemicals. This review first summarizes recent advances in using Xenopus as a vertebrate model to study distinct types of tissue/organ development following exposure to environmental toxicants, chemical reagents, and pharmaceutical drugs. Then, the successful use of Xenopus as a model for diseases, including fetal alcohol spectrum disorders, autism, epilepsy, and cardiovascular disease, is reviewed. The potential application of Xenopus in genetic and chemical screening to protect against embryo deficits induced by chemical toxicants and related diseases is also discussed.
اظهر المزيد [+] اقل [-]tmbim4 protects against triclocarban-induced embryonic toxicity in zebrafish by regulating autophagy and apoptosis
2021
Hu, Zhiyong | He, Liting | Wei, Jiajing | Yufang, Su | Wang, Wei | Fan, Zunpan | Xu, Jia | Zhang, Yuan | Wang, Yongfeng | Peng, Meilin | Zhao, Kai | Zhang, Huiping | Liu, Chunyan
Triclocarban (TCC), an antibacterial agent widely used in personal care products, can affect embryonic development. However, the specific molecular mechanism of TCC-induced embryonic developmental damage remains unclear. In this study, TCC exposure was found to increase the expression of tmbim4 gene in zebrafish embryos. The tmbim4 mutant embryos are more susceptible to TCC exposure than wild-type (WT) embryos, with tmbim4 overexpression reducing TCC-induced embryonic death in the former. Exposure of tmbim4 mutant larvae to 400 μg/L TCC substantially increased apoptosis in the hindbrain and eyes. RNA-sequencing of WT and tmbim4 mutant larvae indicated that knockout of the tmbim4 gene in zebrafish affects the autophagy pathway. Abnormalities in autophagy can increase apoptosis and TCC exposure caused abnormal accumulation of autophagosomes in the hindbrain of tmbim4 mutant zebrafish embryos. Pretreatment of TCC-exposed tmbim4 mutant zebrafish embryos with autophagosome formation inhibitors, substantially reduced the mortality of embryos and apoptosis levels. These results indicate that defects in the tmbim4 gene can reduce zebrafish embryo resistance to TCC. Additionally, apoptosis induced by abnormal accumulation of autophagosomes is involved in this process.
اظهر المزيد [+] اقل [-]Usability of the bivalves Dreissena polymorpha and Anodonta anatina for a biosurvey of the neurotoxin BMAA in freshwater ecosystems
2020
Lepoutre, A. | Hervieux, J. | Faassen, E.J. | Zweers, A.J. | Lurling, M. | Geffard, A. | Lance, E.
The environmental neurotoxin β-methylamino-L-alanine (BMAA) may represent a risk for human health in case of chronic exposure or after short-term exposure during embryo development. BMAA accumulates in freshwater and marine organisms consumed by humans. It is produced by marine and freshwater phytoplankton species, but the range of producers remains unknown. Therefore, analysing the phytoplankton composition is not sufficient to inform about the risk of freshwater contamination by BMAA. Filter-feeders mussels have accumulation capacities and therefore appear to be relevant to monitor various pollutants in aquatic ecosystems. We investigated the suitability of the freshwater mussels Dreissena polymorpha and Anodonta anatina for monitoring BMAA in water. Both species were exposed to 1, 10, and 50 μg of dissolved BMAA/L daily for 21 days, followed by 42 days of depuration in clean water. On days 0, 1, 7, 14, and 21 of exposure and 1, 7, 14, 21 and 42 of depuration, whole D. polymorpha and digestive glands of A. anatina were sampled, and the total BMAA concentration was measured. D. polymorpha accumulated BMAA earlier (from day 1 at all concentrations) and at higher tissue concentrations than A. anatina, which accumulated BMAA from day 14 when exposed to 10 μg BMAA/L and from day 7 when exposed to 50 μg BMAA/L. As BMAA accumulation by D. polymorpha was time and concentration-dependent, with a significant elimination during the depuration period, this species may be able to reflect the levels and dynamics of water contamination by dissolved BMAA. The species A. anatina could be used for monitoring water concentrations above 10 μg BMAA/L.
اظهر المزيد [+] اقل [-]Does microplastic ingestion by zooplankton affect predator-prey interactions? An experimental study on larviphagy
2020
Van Colen, Carl | Vanhove, Brecht | Diem, Anna | Moens, Tom
Litter is omnipresent in the ocean where it can be ingested by marine biota. Although ingestion of microplastics (MPs) is abundantly reported, insights into how MP can influence predator-prey interactions currently limits our understanding of the ecological impact of MPs. Here we demonstrate trophic transfer of MPs from zooplankton to benthic filter feeders, through consumption of contaminated prey (i.e. prey with ingested MP). However, predation rates of contaminated prey were significantly lower as compared to predation rates of prey that had no MPs ingested. As filter feeder clearance rates were not affected by consumption of MPs, the lower predation rates of contaminated prey appear to be primarily explained by disruption in zooplankton swimming behaviour that reduces their filtration risk. This is the first study that shows how MPs can change predator-prey interactions that are involved in the coupling between the pelagic and seabed habitat.
اظهر المزيد [+] اقل [-]High-content screening in zebrafish identifies perfluorooctanesulfonamide as a potent developmental toxicant
2020
Dasgupta, Subham | Reddam, Aalekhya | Liu, Zekun | Liu, Jinyong | Volz, David C.
Per- and polyfluoroalkyl substances (PFASs) have been used for decades within industrial processes and consumer products, resulting in frequent detection within the environment. Using zebrafish embryos, we screened 38 PFASs for developmental toxicity and revealed that perfluorooctanesulfonamide (PFOSA) was the most potent developmental toxicant, resulting in elevated mortality and developmental abnormalities following exposure from 6 to 24 h post fertilization (hpf) and 6 to 72 hpf. PFOSA resulted in a concentration-dependent increase in mortality and abnormalities, with surviving embryos exhibiting a >12-h delay in development at 24 hpf. Exposures initiated at 0.75 hpf also resulted in a concentration-dependent delay in epiboly, although these effects were not driven by a specific sensitive window of development. We relied on mRNA-sequencing to identify the potential association of PFOSA-induced developmental delays with impacts on the embryonic transcriptome. Relative to stage-matched vehicle controls, these data revealed that pathways related to hepatotoxicity and lipid transport were disrupted in embryos exposed to PFOSA from 0.75 to 14 hpf and 0.75 to 24 hpf. Therefore, we measured liver area as well as neutral lipids in 128-hpf embryos exposed to vehicle (0.1% DMSO) or PFOSA from 0.75 to 24 hpf and clean water from 24 to 128 hpf, and showed that PFOSA exposure from 0.75 to 24 hpf resulted in a decrease in liver area and increase in yolk sac neutral lipids at 128 hpf. Overall, our findings show that early exposure to PFOSA adversely impacts embryogenesis, an effect that may lead to altered lipid transport and liver development.
اظهر المزيد [+] اقل [-]DEP and DBP induce cytotoxicity in mouse embryonic stem cells and abnormally enhance neural ectoderm development
2018
Yin, Nuoya | Liang, Shengxian | Liang, Shaojun | Hu, Bowen | Yang, Renjun | Zhou, Qunfang | Jiang, Guibin | Faiola, Francesco
Diethyl phthalate (DEP) and dibutyl phthalate (DBP) are two typical small phthalate esters, extensively used in personal care and consumer products. Although previous studies have linked phthalate esters to several health issues, it is still unclear whether they can affects the early stages of embryonic development. In this study, we evaluated the early developmental neurotoxicity as well as the cytotoxicity of DEP and DBP, using mouse embryonic stem cells (mESCs). Our results showed that both DEP and DBP could decrease mESC viability in a dose-dependent manner. Moreover, while DBP could activate the caspase-3/7 enzymes and cause cell membrane damage as well as intracellular ROS accumulation, interestingly DEP treatment only showed stimulation of ROS production. In addition, DEP and DBP treatment at non-cytotoxic concentrations, abnormally altered the expression levels of several vitally important regulators of embryo development. For instance, neural ectoderm markers, such as Pax6, Nestin, Sox1 and Sox3, were significantly up-regulated upon DEP and DBP exposure. In conclusion, our work suggests a potential developmental toxicity of DEP and DBP on mammals, especially for neural ectoderm specification. Our findings help better understand the association between health problems and DEP/DBP exposure and most significantly remind us of the importance of additional health risk tests for these two largely used chemicals.
اظهر المزيد [+] اقل [-]Microcystin-LR affects the hypothalamic-pituitary-inter-renal (HPI) axis in early life stages (embryos and larvae) of zebrafish
2018
Ma, Yukun | Wang, Yeke | Giesy, John P. | Chen, Feng | Shi, Ting | Chen, Jun | Xie, Ping
Frequencies and durations of blooms of cyanobacteria are increasing. Some cyanobacteria can produce cyanotoxins including microcystins (MCs). MCs are the most common toxic products of hazardous algal blooms (HABs), with the greatest potential for exposure and to cause toxicity. Recently, MCs have been shown to disrupt endocrine functions. In this study, for the first time, effects of MC-LR on the hypothalamic-pituitary-inter-renal (HPI) axis during early embryonic development (embryos/larvae) of zebrafish (Danio rerio), were investigated. Embryos/larvae of zebrafish were exposed to 1, 10, 100, or 300 μg MC-LR/L during the period of 4–168 h post-fertilization (hpf). Exposure to 300 μg MC-LR/L resulted in significantly greater concentrations of whole-body cortisol than those in controls. Expressions of genes along the HPI axis and mineralocorticoid receptor (MR-) and glucocorticoid receptor (GR-) centered gene networks were evaluated by use of quantitative real-time PCR. Expression of mRNA for crh was significantly down-regulated by exposure to 300 μg MC-LR/L, while expressions of crhbp, crhr1, and crhr2 were significantly up-regulated, relative to controls. MC-LR caused significantly lesser levels of mRNA for steroidogenic genes including hmgra, star, and cyp17, but expression of mRNA for hsd20b was significantly greater than that of controls. Treatment with MC-LR also altered profiles of transcription of MR- and GR-centered gene networks, which might result in multiple responses. Taken together, these results demonstrated that MC-LR affected the corticosteroid-endocrine system of larvae of zebrafish. This study provided valuable insights into molecular mechanisms behind potential toxicity and endocrine disruption of MCs.
اظهر المزيد [+] اقل [-]