Nanoplastics, created by the fragmentation of larger plastic debris, are a serious pollutant posing substantial environmental and health risks. Here, we developed a polystyrene nanoparticle (PS-NP) exposure model during mice pregnancy to explore their effects on embryonic development. We found that exposure to 30 nm PS-NPs during pregnancy resulted in reduced mice placental weight and abnormal embryonic development. Subsequently, our transcriptomic dissection unveiled differential expression in 102 genes under PS-NP exposure and the p38 MAPK pathway emerged as being significantly altered in KEGG pathway mapping. Our findings also included a reduction in the thickness of the trophoblastic layer in the placenta, diminished cell invasion capabilities, and an over-abundance of immature red cells in the blood vessels of the mice. In addition, we validated our findings through the human trophoblastic cell line, HTR-8/SVneo (HTR). PS-NPs induced a drop in the vitality and migration capacities of HTR cells and suppressed the p38 MAPK signaling pathway. This research highlights the embryotoxic effects of nanoplastics on mice, while the verification results from the HTR cells suggest that there could also be certain impacts on the human trophoblast layer, indicating a need for further exploration in this area.

Fullerenols, a water-soluble polyhydroxy derivative of fullerene, hold promise in medical and materials science due to their unique properties. However, concerns about their potential embryotoxicity remain. Using a pregnancy mouse model and metabolomics analysis, our findings reveal that fullerenols exposure during pregnancy not only significantly reduced mice placental weight and villi thickness, but also altered the classes and concentrations of metabolites in the mouse placenta. Furthermore, we found that fullerenols exposure reduced the levels of CYP3A4, ERα and estriol (E3), while increasing the levels of estradiol (E2) and oxidative stress both in mouse placenta and placental trophoblast cells, and exogenous supplementation with E3 and ER agonists was effective in restoring these changes in vitro. Moreover, CYP3A4 inhibition was effective in decreasing intracellular E3 levels, whereas overexpression of CYP3A4 resisted the fullerenols-induced decrease in E3 expression Additionally, we synthesized glutathione-modified fullerenols (C60-(OH)n-GSH), which demonstrated improved biocompatibility and reduced embryotoxicity by enhancing intracellular glutathione levels and mitigating oxidative stress. In summary, our results demonstrated that fullerenols exposure decreased E3 synthesis by inhibiting CYP3A4 and exacerbated oxidative stress through downregulation of estrogen receptor activation and decreased glutathione levels. These findings highlight the risks of fullerenols exposure during pregnancy and offer strategies for safer nanomaterial development.

Background: Overweight and obesity are among the leading chronic diseases worldwide. Environmental phenols have been renowned as endocrine disruptors that contribute to weight changes; however, the effects of exposure to mixed phenols on obesity are not well established. Methods: Using data from adults in National Health and Nutrition Examination Survey, this study examined the individual and combined effects of four phenols on obesity. A combination of traditional logistic regression and two mixed models (weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR)) were used together to assess the role of phenols in the development of obesity. The potential mediation of cholesterol on these effects was analyzed through a parallel mediation model. Results: The results demonstrated that solitary phenols except triclosan were inversely associated with obesity (P-value < 0.05). The WQS index was also negatively correlated with general obesity (β: 0.770, 95% CI: 0.644–0.919, P-value = 0.004) and abdominal obesity (β: 0.781, 95% CI: 0.658–0.928, P-value = 0.004). Consistently, the BKMR model demonstrated the significant joint negative effects of phenols on obesity. The parallel mediation analysis revealed that high-density lipoprotein mediated the effects of all four single phenols on obesity, whereas low-density lipoprotein only mediated the association between benzophenol-3 and obesity. Moreover, Cholesterol acts as a mediator of the association between mixed phenols and obesity. Exposure to single and mixed phenols significantly and negatively correlated with obesity. Cholesterol mediated the association of single and mixed environmental phenols with obesity. Conclusions: Assessing the potential public health risks of mixed phenols helps to incorporate this information into practical health advice and guidance.

Nano-antimony trioxide (Nano-Sb₂O₃) is extensively utilized in industrial production and consumer products, leading to widespread environmental contamination and human exposure. Accumulating evidence has demonstrated that Nano-Sb₂O₃ induces male reproductive toxicity, yet the underlying molecular mechanisms remain poorly understood. In this study, male C57BL/6 mice were exposed to Nano-Sb₂O₃ (2.5, 5.0, and 7.5 mg/kg/day). Exposure to Nano-Sb₂O₃ induced dose-dependent reproductive toxicity, evidenced by dose-dependent reductions in sperm motility (56.70% to 36.10%) and sperm density (15.76 × 10⁶/mL to 2.79 × 10⁶/mL) and a marked elevation in sperm malformation rates (4.56% to 44.36%), as well as severe histopathological alterations, testicular Sb accumulation, and elevated reactive oxygen species (ROS) levels. Transcriptomic analysis revealed significant enrichment of the PPAR and PI3K-Akt signaling pathways and identified SPP1 as one of the most significantly differentially expressed genes. Computational pathway perturbation analyses further yielded hypothesis-generating evidence supporting the potential involvement of PPAR signaling suppression and PI3K-Akt and inflammatory pathway activation following Nano-Sb₂O₃ exposure. Both mRNA and protein levels of SPP1 were significantly upregulated in a dose-dependent manner in mouse testes and TM4 Sertoli cells. In vitro experiments further demonstrated that Nano-Sb₂O₃ increased the expression of pro-inflammatory cytokines IL-1β and IL-6 by up to 5.6-fold and 4.7-fold, respectively, while impairing Sertoli cell viability and wound-healing capacity. Importantly, Spp1 silencing attenuated inflammatory responses and restored the expression of blood–testis barrier (BTB)-associated proteins, including ZO-1, Claudin-11, and N-cadherin. These findings suggest that SPP1 may contribute to Nano-Sb₂O₃-induced inflammatory responses and alterations in BTB-associated proteins, thereby potentially participating in male reproductive injury.