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.

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.

Bisphenol A (BPA), an endocrine-disrupting chemical that is largely produced and used in the plastics industry, causes environmental pollution and is absorbed by humans through consumption of food and liquids in polycarbonate containers. BPA exerts developmental and genetic toxicities to embryos and offsprings, but the embryotoxicity mechanism of this chemical is unclear. This study aimed to explore the toxic effect of BPA on embryonic development and elucidate its toxicity mechanism. Embryos of Xenopus laevis as a model were treated with different concentrations (0.1, 1, 10, and 20 μM) of BPA at the two-cell stage to investigate the developmental toxicity of BPA. Embryonic development and behaviors were monitored 24 h–96 h of BPA exposure. BPA concentrations greater than 1 μM exerted significant teratogenic effects on the Xenopus embryos, which showed short tail axis, miscoiled guts, and bent notochord as the main malformations. The 20 μM BPA-treated embryos were seriously damaged in all aspects and exhibited deformity, impaired behavioral ability, and tissue damage. The DNA integrity and apoptosis of the Xenopus embryos were also investigated. Exposure to BPA concentrations higher than 0.1 μM significantly induced DNA damage (p < 0.05). The 10 and 20 μM BPA-treated embryos exhibited higher levels of cleaved caspase-3 protein than the control. The ratios of bax/bcl-2 mRNA were significantly higher in the 10 μM and 20 μM-treated embryos than the ratio in the control group. Overall, data indicated that BPA can delay the early development, induce DNA damage and apoptosis, and eventually cause multiple malformations in Xenopus embryos.

Here, we examined the combinational effect of ocean acidification (OA) and mercury (Hg) in the planktonic copepod Pseudodiaptomus annandalei in cross-factored response to different pCO₂ (400, 800 μatm) and Hg (control, 1.0 and 2.5 μg/L) exposures for three generations (F0–F2), followed by single-generation recovery (F3) under clean condition. Several phenotypic traits and Hg accumulation were analyzed for F0–F3. Furthermore, shotgun-based quantitative proteomics was performed for F0 and F2. Our results showed that OA insignificantly influenced the traits. During F0–F2, combined exposure reduced Hg accumulation as compared with the counterpart Hg treatment, supporting the mitigating effect of OA on Hg toxicity in copepods. Proteomics analysis indicated that the copepods probably increased energy production/storage and stress response to ensure physiological resilience against OA. However, Hg induced many toxic events (e.g., energy depletion and degenerated organomorphogenesis/embryogenesis for F0; cell cycle arrest and detrimental stress-defense for F2), which were translated to the population-level adverse outcome, i.e., compromised growth/reproduction. Particularly, compensatory proteome response was identified (e.g., increased immune defense for F0; energetic compensation and enhanced embryogenesis for F2), accounting for a negative interaction between OA and Hg. Together, this study provides the molecular mechanisms behind the effects of OA and Hg pollution in marine copepods.

Little is known about the fate of oil spills in rivers. Hyporheic flows of water through river sediments exchange surface and groundwater and create upwelling and downwelling zones that are important for fish spawning and embryo development. Risk assessments of oil spills to rivers do not consider the potential for hyporheic flows to carry oil droplets into sediments and the potential for prolonged exposure of fish to trapped oil. This project assessed whether oil droplets in water flowing through gravel will be trapped and whether hydrocarbons partitioning from trapped oil droplets are bioavailable to fish. Columns packed with gravel were injected with oil-in-water dispersions prepared with light crude, medium crude, diluted bitumens, and heavy fuel oil to generate a series of oil droplet loadings. The concentrations of oil trapped in the gravel increased with oil loading and viscosity. When the columns were perfused with clean water, oil concentrations in column effluents decreased to the detection limit within the first week of water flow, with sporadically higher concentrations associated with oil droplet release. Despite the low concentrations of hydrocarbons measured in column effluent, hydrocarbons were bioavailable to juvenile rainbow trout (Oncorhynchus mykiss) for more than three weeks of water flow, as indicated by strong induction of liver ethoxyresorufin-o-deethylase activity. These findings indicate that ecological risk assessments and spill response should identify and protect areas in rivers sensitive to contaminant trapping.

Endocrine-disrupting chemicals (EDCs) are compounds that interfere with the expression, synthesis, and activity of hormones in organisms. They are released into the environment from flame retardants and products containing plasticizers. Persistent pesticides, such as dichlorodiphenyltrichloroethane (DDT) and hexachlorobenzene, also disrupt the endocrine system through interaction with hormone receptors. Endogenous hormones, such as 17β-estradiol (E2), are released in the urine and feces of farm animals and seep into terrestrial and aquatic ecosystems through sewage. Pigs are widely used as animal models to determine the effects of EDCs because they are physiologically, biochemically, and histologically similar to humans. EDCs primarily disrupt the reproductive and nervous systems of pigs. Moreover, embryonic development during the prenatal and early postnatal periods is particularly sensitive to EDCs. Mycotoxins, such as zearalenone, are food contaminants that alter hormonal activities in pigs. Mycotoxins also alter the innate immune system in pigs, making them vulnerable to diseases. It has been reported that farm animals are exposed to various types of EDCs, which accumulate in tissues, such as those of gonads, livers, and intestines. There is a lack of an integrated understanding of the impact of EDCs on porcine reproduction and development. Thus, this article aims to provide a comprehensive review of literature regarding the effects of EDCs in pigs.

Diclofop-methyl (DM) is one of the most widely used herbicides in agriculture production and has been frequently detected in both freshwater and environments, even agricultural products. However, the potential toxic effects of DM on organisms and the underlying mechanisms are still poorly understood. In this study, we utilized zebrafish to evaluate the toxicity of DM during the cardiovascular developmental process. Exposure of zebrafish embryos to 0.75, 1.0 and 1.25 mg/L DM induced cardiac defects, such as pericardial edema, slow heart rate and long SV-BA distance but the vascular development in zebrafish larvae was not influenced by DM treatment. The expression of cardiac-related genes were disordered and DM exposure initiated disordering cardiogenesis from the period of precardiac mesoderm formation. Moreover, the apoptosis and proliferation of cardiomyocytes were not influenced but the levels of oxidative stress were upregulated by DM exposure. Fullerenes and astaxanthin was able to rescue cardiac defects caused by DM via downregulating oxidative stress. Wnt signaling was downregulated after DM treatment and activation of Wnt signaling could rescue cardiac defects. Therefore, our results suggest that DM has the potential to induce cardiac developmental toxicity through upregulation of Wnt-Mediated (reactive oxygen species) ROS generation in zebrafish larvae.

The emerging flame retardants pentabromobenzene (PBB) has been frequently detected in recent years and may pose exposure risks to wild animals and human beings. In this study, the inflation of posterior swim bladder of zebrafish larvae was used as an endpoint to study the developmental toxicity and putative mechanisms associated with PBB toxicity. Our results showed that embryonic exposure to PBB could significantly inhibit the inflation of posterior swim bladders. Reduced T3 levels and transcriptional changes of crh and pomc were observed in PBB treated zebrafish larvae at 120 hpf. However, key regulators of thyroid and adrenocortical system involved in the synthesis (tsh), biological conversion (ugt1ab, dio2) and functional regulation (trα, trβ, gr) showed no significant changes. Further data revealed that prlra was the only gene that was altered among the detected genes at 96 h post fertilization (hpf). At 120 hpf, the morphology of swim bladder indicated deflation in treatments at 0.25 μM and higher. In addition, the mRNA levels of anxa5, prlra, prlrb, atp1b2 and slc12a10 were all significantly changed at 120 hpf. Taken together, we suppose that embryonic exposure to PBB inhibited the inflation of swim bladder in zebrafish probably via prlra mediated pathways. The observed changes of thyroid and adrenocortical parameters might be indirect effects evoked by PBB exposure. Overall, our results provide important data and indications for future toxicological study and risk assessment of the emerging flame retardants PBB.

Pesticides scarcely exist as individual compounds in the water ecosystem, but rather as mixtures of multiple chemicals at relatively low concentrations. In this study, we aimed to explore the mixture toxic effects of fludioxonil (FLU) and triadimefon (TRI) on zebrafish (Danio rerio) by employing different toxicological endpoints. Results revealed that the 96-h LC₅₀ values of FLU to D. rerio at multiple developmental stages ranged from 0.055 (0.039–0.086) to 0.61 (0.33–0.83) mg L⁻¹, which were less than those of TRI ranging from 3.08 (1.84–5.96) to 9.75 (5.99–14.78) mg L⁻¹. Mixtures of FLU and TRI exerted synergistic effects on embryonic zebrafish. Activities of total superoxide dismutase (T-SOD) and catalase (CAT) were markedly altered in most of the individual and pesticide mixture treatments compared with the control. The expressions of 16 genes involved in oxidative stress, cellular apoptosis, immune system and endocrine system displayed that embryonic zebrafish were affected by the individual pesticides and their mixtures, and greater variations of four genes (ERɑ, Tnf, IL and bax) were found when exposed to pesticide mixtures compared with their individual compounds. Therefore, more studies on mixture toxicities among different pesticides should be taken as a priority when evaluating their ecological risk.

We previously found that folic acid (FA) attenuated cardiac defects in zebrafish embryos exposed to extractable organic matter (EOM) from PM2.5, but the underlining mechanisms remain to be elucidated. Since DNA methylation is crucial to cardiac development, we hypothesized that EOM-induced aberrant DNA methylation changes could be diminished by FA supplementation. In this study, zebrafish embryos were exposed to EOM in the absence or presence of FA. Genomic-wide DNA methylation analysis identified both DNA hypo- and hyper-methylation changes in CCGG sites in zebrafish embryos exposed to EOM, which were attenuated by FA supplementation. We identified a total of 316 genes with extensive DNA methylation changes in EOM samples but little or no DNA methylation changes in EOM plus FA samples. The genes were involved in critical cellular processes and signaling pathways important for embryo development. In addition, the EOM-decreased SAM/SAH ratio was counteracted by FA supplementation. Furthermore, FA attenuated the EOM-induced changes in the expression of genes involved in the regulation of DNA methylation and in folate biosynthesis. In conclusion, our data suggest that FA supplementation protected zebrafish embryos from the cardiac developmental toxicity of PM2.5 by alleviating EOM-induced DNA methylation changes.