Transgenerational Effects and Mechanisms of Tributyltin Exposure on Neurodevelopment in the Male Offspring of Rats.

This study aimed to investigate the transgenerational effects of tributyltin exposure on rat neurodevelopment in male offspring and the potential mechanisms. Neonatal female rats were exposed to the environmental level of tributyltin and then mated with nonexposed males after sexual maturity to produce the F1 generation. The F1 generation (with primordial germ cell exposure) was mated with nonexposed males to produce nonexposed offspring (the F2 and F3 generations). Neurodevelopmental indicators and behavior were observed for the F1, F2, and F3 generations during postnatal days 1-25 and 35-56, respectively. We found premature eye-opening and delayed visual positioning in newborn F1 rats and anxiety and cognitive deficits in prepubertal F1 male rats. These neurodevelopmental impacts were also observed in F2 and F3 males. Additionally, F1-F3 males exhibited increased serotonin and dopamine levels and a loose arrangement of neurons in the hippocampus. We also observed a reduction in the expression of genes involved in intercellular adhesion and increased DNA methylation of the Dsc3 promoter in F1-F3 males. We concluded that tributyltin exposure led to transgenerational effects on neurodevelopment via epigenetic reprogramming in male offspring. These findings provide insights into the risks of neurodevelopmental disorders in offspring from parents exposed to tributyltin.

The valence state of iron-based nanomaterials determines the ferroptosis potential in a zebrafish model.

Many nanomaterials containing different valences of iron have been designed for applications in biomedicine, energy, catalyzers, nanoenzymes, and so on. However, the toxic effects of the valence state of iron in iron-based nanomaterials are still unclear. Here, three different-valence iron-based nanomaterials (nFe@Fe3O4, nFe3O4 and nFe2O3) were synthesized and exposed to zebrafish embryos and mammalian cardiomyocytes. All of them induced ferroptosis along with an increase in valence through iron overload and the Fenton reaction. Specifically, we exposed Tg (cmlc2:EGFP) zebrafish to the three iron-based nanomaterials and found that nFe@Fe3O4 treatments led to enlarged ventricles, while nFe3O4 and nFe2O3 increased atrial size, which was consistent with the results from hematoxylin-eosin staining and in situ hybridization. Moreover, we used ferroptosis inhibitors (ferrostatin-1 or deferoxamine) to treat zebrafish along with nanoparticles exposure and found that the cardiac developmental defects caused by nFe3O4 and nFe2O3, but not nFe@Fe3O4, could be completely rescued by ferroptosis inhibitors. We further found that nFe@Fe3O4, rather than nFe3O4 and nFe2O3, reduced the dissolved oxygen in the medium, which resulted in hypoxia and acceleration of heart tube formation and ventricular enlargement, and both were fully rescued by oxygen donors combined with ferroptosis inhibitors. Consistently, these findings were also observed in mammalian cardiomyocytes. In summary, our study demonstrates that the valence state of iron-based nanomaterials determines the ferroptosis potential. Our study also clarifies that high-valence iron-based nanomaterials induce an enlarged atrium via ferroptosis, while low-valence ones increase the ventricular size through both hypoxia and ferroptosis, which is helpful to understand the potential adverse effects of different valences of iron-based nanomaterials on environmental health and assure the responsible and sustainable development of nanotechnology.

Elevated lead levels from e-waste exposure are linked to sensory integration difficulties in preschool children.

Exposure to lead is associated with adverse effects on neurodevelopment. However, studies of the effects of lead on sensory integration are few. The purpose of this research is to investigate the effect of lead exposure on child sensory integration by correlating the blood lead levels of children with sensory processing measures. A total of 574 children, from 3 to 6 years of age, 358 from an electronic waste (e-waste) recycling town named Guiyu, and 216 from Haojiang, a nearby town with no e-waste recycling activity, were recruited in this study. The median blood lead level in Guiyu children was 4.88 µg/dL, higher than the 3.47 µg/dL blood lead level in Haojiang children (P < 0.001). 47.2% of Guiyu children had blood lead levels exceeding 5 µg/dL. The median concentration of serum cortisol, an HPA-axis biomarker, in Guiyu children was significantly lower than in Haojiang, and was negatively correlated with blood lead levels. All subscale scores and the total score of the Sensory Processing Measure (Hong Kong Chinese version, SPM-HKC) in Guiyu children were higher than Haojiang children, indicating greater difficulties, especially for touch, body awareness, balance and motion, and total sensory systems. Sensory processing scores were positively correlated with blood lead, except for touch, which was negatively correlated with serum cortisol levels. Simultaneously, all subscale scores and the total SPM-HKC scores for children with high blood lead levels (blood lead > 5 µg/dL) were higher than those in the low blood lead level group (blood lead < 5 µg/dL), especially for hearing, touch, body awareness, balance and motion, and total sensory systems. Our findings suggest that lead exposure in e-waste recycling areas may result in a decrease in serum cortisol levels and an increase in child sensory integration difficulties. Cortisol may be involved in touch-related sensory integration difficulties.

Proteomic evaluation of human umbilical cord tissue exposed to polybrominated diphenyl ethers in an e-waste recycling area.

Parental exposure to polybrominated diphenyl ethers (PBDEs) is associated with adverse birth outcomes. This study aims to examine differentially-expressed protein profiles in umbilical cord tissue, derived from mothers exposed to PBDEs, and investigate candidate biomarkers to reveal the underlying molecular mechanisms. Umbilical cord samples were obtained from women residing in an electronic waste (e-waste) recycling area (Guiyu) and reference area (Haojiang) in China. The concentration of PBDEs in umbilical cord tissue was determined by gas chromatography and mass spectrometry (GC/MS). Isobaric tagging for relative and absolute quantification (iTRAQ)-based proteomic technology was conducted to analyze differentially-expressed protein profiles. The total PBDE concentration was approximately five-fold higher in umbilical cords from Guiyu than from Haojiang (median 71.92ng/g vs. 15.52ng/g lipid, P<0.01). Neonatal head circumference, body-mass index (BMI) and Apgar1 score were lower in Guiyu and negatively correlated with PBDE concentration (P<0.01). Proteomic analysis showed 697 proteins were differentially expressed in the e-waste-exposed group compared with the reference group. The differentially-expressed proteins were principally involved in antioxidant defense, apoptosis, cell structure and metabolism. Among them, catalase and glutathione S-transferase omega-1, were down-regulated, and cytochrome c was found to be up-regulated, changes which were further verified by enzyme-linked immunosorbent assays. These results suggest that an antioxidant imbalance and cell apoptosis in the umbilical cord following PBDE exposure is associated with neonatal birth outcomes.