Nanopolystyrene Translocation and Fetal Deposition After Acute Lung Exposure During Late-Stage Pregnancy

Fournier, Sara; D’Errico, Jeanine N; Adler, Derek; Kollontzi, Stamatina; Goedken, Michael; Fabris, Laura; Yurkow, Edward J.; Stapleton, Phoebe A.

doi:10.21203/rs.3.rs-39676/v1

Cited by 9 publications

(11 citation statements)

References 56 publications

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“…If negative health consequences persist into the F3 generation, without subsequent exposure, this is considered a transgenerational effect because these offspring have never been exposed to particles or a hostile gestational environmental associated with the original F0 insult [7]. Nano-TiO 2 has been shown to cross the placenta [8] during gestational exposure and potentially deposits into the pup [9], however perturbations in vasoreactivity within the uterus of the dam and/or the placenta of the pup alone are enough to result in detrimental fetal health consequences [10].…”

Section: Introductionmentioning

confidence: 99%

Nano-titanium dioxide inhalation exposure during gestation drives redox dysregulation and vascular dysfunction across generations

et al. 2022

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Background Pregnancy is associated with many rapid biological adaptations that support healthy development of the growing fetus. One of which is critical to fetal health and development is the coordination between maternal liver derived substrates and vascular delivery. This crucial adaptation can be potentially derailed by inhalation of toxicants. Engineered nanomaterials (ENM) are commonly used in household and industrial products as well as in medicinal applications. As such, the potential risk of exposure remains a concern, especially during pregnancy. We have previously reported that ENM inhalation leads to upregulation in the production of oxidative species. Therefore, we aimed to determine if F0 dam maternal nano-TiO2 inhalation exposure (exclusively) resulted in altered H2O2 production capacity and changes in downstream redox pathways in the F0 dams and subsequent F1 pups. Additionally, we investigated whether this persisted into adulthood within the F1 generation and how this impacted F1 gestational outcomes and F2 fetal health and development. We hypothesized that maternal nano-TiO2 inhalation exposure during gestation in the F0 dams would result in upregulated H2O2 production in the F0 dams as well as her F1 offspring. Additionally, this toxicological insult would result in gestational vascular dysfunction in the F1 dams yielding smaller F2 generation pups. Results Our results indicate upregulation of hepatic H2O2 production capacity in F0 dams, F1 offspring at 8 weeks and F1 females at gestational day 20. H2O2 production capacity was accompanied by a twofold increase in phosphorylation of the redox sensitive transcription factor NF-κB. In cell culture, naïve hepatocytes exposed to F1-nano-TiO2 plasma increased H2O2 production. Overnight exposure of these hepatocytes to F1 plasma increased H2O2 production capacity in a partially NF-κB dependent manner. Pregnant F1- nano-TiO2 females exhibited estrogen disruption (12.12 ± 3.1 pg/ml vs. 29.81 ± 8.8 pg/ml sham-control) and vascular dysfunction similar to their directly exposed mothers. F1-nano-TiO2 uterine artery H2O2 production capacity was also elevated twofold. Dysfunctional gestational outcomes in the F1-nano-TiO2 dams resulted in smaller F1 (10.22 ± 0.6 pups vs. sham-controls 12.71 ± 0.96 pups) and F2 pups (4.93 ± 0.47 g vs. 5.78 ± 0.09 g sham-control pups), and fewer F1 male pups (4.38 ± 0.3 pups vs. 6.83 ± 0.84 sham-control pups). Conclusion In conclusion, this manuscript provides critical evidence of redox dysregulation across generations following maternal ENM inhalation. Furthermore, dysfunctional gestational outcomes are observed in the F1-nano-TiO2 generation and impact the development of F2 offspring. In total, this data provides strong initial evidence that maternal ENM exposure has robust biological impacts that persists in at least two generations.

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Section: Introductionmentioning

confidence: 99%

Nano-titanium dioxide inhalation exposure during gestation drives redox dysregulation and vascular dysfunction across generations

et al. 2022

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“…The morphology and particle size of inhaled PM 2.5 or UFPs in the human body are usually characterized by microscopic techniques, including optical and electron microscopies. 14,16,24,25 A variety of optics-based microscopic techniques have been developed in recent years (e.g., confocal laser scanning microscopy (CLSM) 26,27 and enhanced hyperspectral microscopy 28,29 ), making the detection of PM 2.5 in biological tissues much easier. Compared with optical microscopy, electron microscopic (EM) techniques with transmission electron microscopy (TEM) and scanning electron microscopy (SEM) being the most used are more suitable for characterizing PM 2.5 or UFPs because of their simpler pretreatment (e.g., without dyeing), higher magnification, and more powerful qualitative capacities when being equipped with other accessories (e.g., EDX or EELS).…”

Section: Of Pm 25 and The Corresponding Methodologiesmentioning

confidence: 99%

Internal Exposure and Distribution of Airborne Fine Particles in the Human Body: Methodology, Current Understandings, and Research Needs

Weichao

Lin

Yang

et al. 2022

Environ. Sci. Technol.

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Exposure to airborne fine particles (PM 2.5 , particulate matter with aerodynamic diameter <2.5 μm) severely threatens global human health. Understanding the distribution and processes of inhaled PM 2.5 in the human body is crucial to clarify the causal links between PM 2.5 pollution and diseases. In contrast to extensive research on the emission and formation of PM 2.5 in the ambient environment, reports about the occurrence and fate of PM 2.5 in humans are still limited, although many studies have focused on the exposure and adverse effects of PM 2.5 with animal models. It has been shown that PM 2.5 , especially ultrafine particles (UFPs), have the potential to go across different biological barriers and translocate into different human organs (i.e., blood circulation, brain, heart, pleural cavity, and placenta). In this Perspective, we summarize the factors affecting the internal exposure of PM 2.5 and the relevant analytical methodology and review current knowledge about the exposure pathways and distribution of PM 2.5 in humans. We also discuss the research challenges and call for more studies on the identification and characterization of key toxic species of PM 2.5 , quantification of internal exposure doses in the general population, and further clarification of translocation, metabolism, and clearance pathways of PM 2.5 in the human body. In this way, it is possible to develop toxicity-based air quality standards instead of the currently used mass-based standards.

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“…Although the significance is still to be determined, maternally inhaled pollutants can translocate to the developing fetus. Studies have demonstrated the deposition of the inhaled pollutants in the placenta (Liu et al, 2021) and other organs within the fetus (Fournier et al, 2020). Recognizing the risk for lifelong health ramifications, efforts should be made to decrease the incidence of premature births associated with prenatal exposure to unhealthy air.…”

Section: Pregnancymentioning

confidence: 99%

Easy Breathing: A Review of the Impact of Air Quality on Pediatric Health Outcomes

Gonzales¹,

Whalen²

2022

Journal of Pediatric Health Care

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Preventable environmental factors such as exposure to poor air quality are predicted to affect 23% of all global deaths. Although there have been efforts to reduce air pollution through federal guidelines for vehicle and industrial emissions, the air in the United States remains far from clean. Children and pregnant women have been identified as high-risk populations who are particularly susceptible to the negative effects of poor air quality. This paper provides an overview of health concerns related to poor air quality, pediatric considerations from pregnancy through childhood, the importance of increased awareness of air quality assessment and prevention in patient encounters, and current advocacy efforts and legislation.

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Nanopolystyrene Translocation and Fetal Deposition After Acute Lung Exposure During Late-Stage Pregnancy

Cited by 9 publications

References 56 publications

Nano-titanium dioxide inhalation exposure during gestation drives redox dysregulation and vascular dysfunction across generations

Nano-titanium dioxide inhalation exposure during gestation drives redox dysregulation and vascular dysfunction across generations

Internal Exposure and Distribution of Airborne Fine Particles in the Human Body: Methodology, Current Understandings, and Research Needs

Easy Breathing: A Review of the Impact of Air Quality on Pediatric Health Outcomes

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