![Toxic Effects of Benzo[a]pyrene on Pancreatic Development and Function in Offspring Rats](https://lh3.googleusercontent.com/d/1OWy05TaACX1MxzRB7byJ1rsjoXvoNne0)
Key Takeaways & Executive Findings
- •• • Intrauterine BaP exposure at 800 and 1600 μg·kg−1 induced dose-dependent pancreatic damage in offspring, characterized by disrupted islet morphology and reduced islet area, which persisted from postnatal day 2 to week 12, indicating irreversible developmental toxicity. • • PDX-1 and TFAM protein and mRNA expression were significantly downregulated in a dose-dependent manner in both 2-day and 12-week offspring, suggesting molecular mechanisms linking BaP exposure to impaired pancreatic development and mitochondrial dysfunction. • • At week 12, the 1600 μg·kg−1 BaP group showed pre-diabetic symptoms, with significantly elevated blood glucose at 120 min post-glucose challenge (P<0.01) and slower glucose clearance during IPITT (P<0.05 at 30, 60, 120 min), indicating impaired glucose tolerance and insulin resistance. • • The area under the curve (AUC) for IPGTT and IPITT in the 1600 μg·kg−1 group was significantly higher than control (P<0.01), confirming functional impairment of pancreatic β-cells and systemic insulin resistance, which may increase long-term risk of type 2 diabetes.
Abstract
This study investigated the toxic effects of intrauterine benzo[a]pyrene (BaP) exposure on pancreatic development and glucose metabolism in first-generation offspring rats. Pregnant Wistar rats were randomly divided into control and treatment groups receiving 200, 800, or 1600 μg·kg−1 BaP via daily oral gavage during gestation until delivery. Pancreatic histology was assessed in offspring at postnatal day 2 and week 12. Protein and mRNA expression of pancreatic duodenal homeobox-1 (PDX-1) and mitochondrial transcription factor A (TFAM) were quantified. Intraperitoneal glucose tolerance tests (IPGTT) and insulin tolerance tests (IPITT) were performed at week 12. Results showed that exposure to 800 and 1600 μg·kg−1 BaP caused dose-dependent pancreatic damage, with more severe islet morphological disruption and reduced islet area, which did not improve with age. PDX-1 and TFAM expression levels decreased in a dose-dependent manner at both time points. At week 12, the 1600 μg·kg−1 group exhibited pre-diabetic symptoms, including elevated blood glucose and insulin levels, and impaired glucose tolerance and insulin sensitivity. These findings indicate that intrauterine BaP exposure leads to persistent pancreatic developmental impairment and glucose metabolism disorders, potentially mediated by downregulation of PDX-1 and TFAM, with no recovery over time.
1. Introduction
Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental pollutants with well-documented carcinogenic, teratogenic, and mutagenic properties. Among them, benzo[a]pyrene (BaP) is a prototypical endocrine disruptor that enters the human body through inhalation of particulate matter, vehicle exhaust, and heating emissions. BaP metabolites can cross the placental barrier, exerting embryotoxicity that restricts fetal growth and leads to low birth weight and organ developmental defects. Such prenatal insults are increasingly linked to metabolic disorders in adulthood, including obesity, fatty liver, and diabetes. However, the specific impact of intrauterine BaP exposure on pancreatic development and long-term glucose homeostasis remains poorly understood.
This study addresses the critical gap by employing a rat model with gestational BaP exposure at environmentally relevant doses (200–1600 μg·kg−1). We systematically evaluated pancreatic histology, expression of key transcription factors PDX-1 and TFAM, and functional outcomes via glucose and insulin tolerance tests. The results demonstrate dose-dependent and persistent pancreatic damage, with significant downregulation of PDX-1 and TFAM, culminating in pre-diabetic phenotypes. These findings provide mechanistic insights into the developmental origins of metabolic disease and underscore the need for stricter environmental regulations on PAH exposure during pregnancy.
Loading authentic research manuscript (Pages 1–5)...
CUI Rong, CHENG Yi, ZHAI Xiaohe, WANG Li, LU Ying (2026). Toxic Effects of Benzo[a]pyrene on Pancreatic Development and Function in Offspring Rats. Environmental Chemistry. https://doi.org/10.7524/j.issn.0254-6108.2025021101
Research & Educational Purpose Only: The translations, structured abstracts, analytical annotations, and data reports provided by SinoGreenTechare intended exclusively for academic research, internal corporate R&D, and educational benchmarking. They do not constitute formal engineering, chemical safety, legal, or professional advice.
Copyright & Intellectual Property Notice: Original copyright of the underlying source articles and experimental data remains with the respective authors, institutions, and original publishing journals. SinoGreenTech claims intellectual property only over its proprietary translations, analytical syntheses, and AEO structured enhancements in accordance with international fair use and academic citation principles.
Frequently Asked Questions
What are the specific molecular mechanisms by which BaP downregulates PDX-1 and TFAM expression in pancreatic tissue?
The study observed significant downregulation of PDX-1 and TFAM at both protein and mRNA levels in a dose-dependent manner. While the exact mechanism was not fully elucidated, it is hypothesized that BaP metabolites may induce oxidative stress and mitochondrial dysfunction, leading to epigenetic modifications or transcription factor inhibition. Further studies are needed to identify upstream signaling pathways.
How does the observed pancreatic damage correlate with the severity of glucose intolerance and insulin resistance in offspring?
At 12 weeks, the 1600 μg·kg−1 group exhibited significantly higher blood glucose at 120 min post-glucose load (P<0.01) and slower glucose clearance during IPITT (P<0.05 at 30, 60, 120 min), indicating impaired β-cell function and insulin resistance. The AUC for both tests was significantly elevated (P<0.01), confirming a direct correlation between pancreatic structural damage and functional metabolic impairment.
Is the pancreatic damage reversible if offspring are removed from BaP exposure after birth?
No, the damage appears irreversible. The study assessed offspring at postnatal day 2 and week 12, and the pancreatic histological abnormalities and reduced PDX-1/TFAM expression persisted without improvement, even though the offspring were not directly exposed postnatally. This suggests that intrauterine exposure causes permanent developmental programming changes.
What are the implications of these findings for human risk assessment of PAH exposure during pregnancy?
The study provides strong evidence that gestational BaP exposure at doses relevant to environmental contamination can cause lasting pancreatic dysfunction and increase diabetes risk in offspring. This underscores the need for stricter air quality standards and biomonitoring of PAH levels in pregnant women, as well as early metabolic screening for children born to exposed mothers.
How do the BaP exposure doses used in this study compare to real-world human exposure levels?
The doses (200–1600 μg·kg−1) are higher than typical daily human intake but are commonly used in rodent toxicology studies to elicit observable effects. Human exposure is often chronic and low-dose, but the developing fetus is particularly vulnerable. The study's dose-response relationship suggests that even lower doses might pose risks, warranting further investigation using physiologically based pharmacokinetic modeling.
Related Chinese Research & Cross-Citations
Exploring the Potential Molecular Mechanisms of Eight Environmental Pollutants in Lung Adenocarcinoma through Network Toxicology, Machine Learning, and Multi-Omics Analysis
Epidemiological studies have established a significant association between exposure to environmental pollutants (EP) and the risk of lung adenocarcinoma (LUAD). This study integrates network toxicology and multi-omics analysis to elucidate the EP-LUAD molecular regulatory network and identify key regulatory genes, thereby revealing novel mechanisms of environmental carcinogenesis. Transcriptomic data from GEO and TCGA databases yielded 4,971 and 4,488 disease-related targets, respectively. Integration of toxicology databases (TargetNet, Swiss Target Prediction, CTD, SEA) identified 24,860 potential targets for eight common pollutants (SO2, NO, CO, NO2, O3, benzene, toluene, and polycyclic aromatic hydrocarbons). Intersection of these datasets produced 1,536 EP-LUAD common target genes. Protein-protein interaction network analysis identified 247 core targets. Machine learning selected five key genes: AGER, CAV1, CD44, CEP55, and GNB3, which demonstrated robust diagnostic and prognostic efficacy. Their expression correlated with immune cell infiltration, including CD4+ memory T cells and macrophages. Single-cell RNA sequencing revealed epithelial cell-specific expression patterns. Molecular docking confirmed stable pollutant-target binding, with PAH showing highest affinity for CD44 (binding energy −9.32 kcal·mol−1) and GNB3 (−8.32 kcal·mol−1). These findings establish AGER, CAV1, CD44, CEP55, and GNB3 as core molecular mediators of pollution-related LUAD. The high-affinity binding of PAH to CD44 and GNB3 underscores its carcinogenic potential. This study constructs a multi-level regulatory network for EP-LUAD, revealing underlying molecular mechanisms and providing novel potential targets and theoretical basis for early warning and intervention.
Effects of Different Functionalized Nanoplastics on the Transformation of Extracellular Antibiotic Resistance Genes in Aquatic Environments
The rapid dissemination of antibiotic resistance genes (ARGs) in aquatic environments poses serious threats to public health and environmental safety under the 'One Health' framework. Nanoplastics (NPs), as co-occurring pollutants, can exacerbate ARG risks by promoting horizontal gene transfer (HGT), yet the influence of different functional groups on extracellular ARG (eARG) transformation remains unclear. This study investigated the effects of carboxy-modified polystyrene NPs (PS-COOH) and amino-functionalized polystyrene NPs (PS-NH2) compared to unmodified polystyrene NPs (PS) on the transformation of the extracellular resistance plasmid IE-V1955 (carrying an ampicillin resistance gene) into Escherichia coli DH5α. Results showed that PS-COOH exposure promoted plasmid transformation similarly to PS, with effects increasing over 0.1–20 mg·L−1. Low concentrations (0.1–0.5 mg·L−1) of PS-NH2 also enhanced transformation, with stronger effects than PS-COOH at equal doses, whereas high concentrations (1–20 mg·L−1) inhibited it. Mechanistically, PS-COOH (0.1–20 mg·L−1) and low PS-NH2 induced intracellular reactive oxygen species (ROS), increased cell membrane permeability, elevated the protein-to-polysaccharide ratio in extracellular polymeric substances (EPS), and promoted biofilm formation, thereby facilitating transformation. High PS-NH2 concentrations caused excessive ROS leading to cell lysis and formed aggregates with plasmids larger than membrane pores, blocking uptake. These findings provide a theoretical basis for assessing the combined environmental health risks of NPs and ARGs.
Cardiovascular Toxicity Induced by Micro/Nano-Plastics and Its Mechanisms
Micro/nano-plastics (MNPs) are emerging contaminants widely detected in human circulatory systems, including blood, heart, and vascular endothelium, raising concerns about cardiovascular health risks. This systematic review analyzed 61 peer-reviewed studies (2008–2024) to elucidate the cardiotoxic effects and molecular mechanisms of MNPs. Evidence indicates that MNPs exposure elevates risks of atherosclerosis, thrombosis, and arrhythmias through oxidative stress, inflammatory cascades, endothelial dysfunction, and metabolic dysregulation. Notably, co-exposure with persistent organic pollutants (POPs) or heavy metals may produce synergistic or antagonistic effects. Current research relies predominantly on animal and cell models, with critical gaps in low-dose, long-term exposure data and epidemiological evidence. Future studies should optimize experimental designs, integrate metabolomics and epigenetics, and explore transgenerational effects and combined toxicity mechanisms to inform pollution control policies and mitigate cardiovascular risks.
Body Burden of Polybrominated Diphenyl Ethers and Joint Effects on Thyroid Function in a Physical Examination Population in Shenzhen
This study characterized the body burden of polybrominated diphenyl ethers (PBDEs) in a physical examination population in Shenzhen and evaluated its impact on thyroid function. Serum samples from 368 residents were analyzed for eight PBDE congeners using atmospheric pressure gas chromatography-tandem mass spectrometry (APGC-MS/MS). The median concentration of ∑8PBDEs was 10.2 ng·g⁻¹ lipid weight (lw), ranging from 0.13 to 2089.4 ng·g⁻¹ lw, with BDE-209 predominating (59.7% of total). Multiple linear regression revealed that a 1.7-fold increase in serum BDE-153 was associated with a 0.4% increase in free triiodothyronine (FT3) (P<0.05), while a 1.7-fold increase in BDE-183 was associated with a 0.9% decrease in total triiodothyronine (T3) and a 0.7% decrease in FT3 (P<0.05). Bayesian kernel machine regression (BKMR) indicated a negative correlation between mixed PBDE exposure and thyroid-stimulating hormone (TSH) at high exposure levels. Weighted quantile sum (WQS) regression showed that mixed exposure was associated with decreased T3 levels and T3/FT3 ratio, with BDE-153 and BDE-183 as the primary contributors. These findings suggest that PBDE exposure may adversely affect thyroid function and disrupt thyroid hormone homeostasis, with BDE-183 and BDE-153 playing key roles. This study provides a scientific basis for PBDE health risk assessment and thyroid protection.
Mechanisms of Natural Organic Matter in Regulating Microplastic Aggregation and Transport in Soil-Groundwater Systems: A Review
Microplastics (MPs) are persistent emerging contaminants ubiquitously distributed in soil-groundwater environments, where their aggregation and transport critically govern pollutant fate and ecological risks. Natural organic matter (NOM), a complex assemblage of organic compounds, interacts with MPs and porous media via hydrogen bonding, π-π interactions, hydrophobic effects, and electrostatic binding, thereby modulating MP surface properties and environmental behavior. This review systematically synthesizes the mechanisms by which NOM influences MP aggregation and transport, with emphasis on the distinct roles of humic substances, proteins, and extracellular polymeric substances (EPS), and their synergistic modulation with solution chemistry (pH, ionic strength, ion type). Additionally, NOM accelerates MP aging and alters surface characteristics, consequently impacting transport capacity. Current research limitations are identified, and future directions are proposed to inform MP pollution risk assessment and management strategies. Key findings indicate that NOM generally enhances MP stability and mobility at low ionic strengths, while high ionic strengths may induce aggregation depending on NOM type and ion valence. Humic substances predominantly increase electrostatic repulsion, whereas proteins and EPS can bridge particles, promoting aggregation. Aging processes, accelerated by NOM photochemical activity, increase surface oxygen functionality and hydrophilicity, further altering transport. The review underscores the need for systematic studies under environmentally relevant conditions to predict MP fate accurately.
Neurotoxicity of Carboxyl-Modified Polystyrene Microplastics on Zebrafish at Early Developmental Stage
Carboxyl-modified polystyrene microplastics (PS-COOH) are negatively charged particles formed by surface oxidation and functional group modification of polystyrene microplastics (PS), widely used in biomedical and analytical chemistry. However, studies on their neurotoxic effects on aquatic organisms are scarce. This study employed zebrafish (Danio rerio) as a model organism, exposing embryos to environmentally relevant concentrations (0.1, 1, 10, 100 μg·L−1) of PS and PS-COOH. Neurotoxic effects were assessed by measuring tail coiling frequency at 24 hpf and swimming velocity under alternating light/dark cycles at 120 hpf. Results demonstrated that both PS and PS-COOH induced neurotoxicity, with PS-COOH significantly reducing tail coiling frequency and average swimming speed compared to PS (P<0.05). Exposure to 10 μg·L−1 PS-COOH disrupted neurotransmitter homeostasis, altering levels of acetylcholine (ACh), serotonin (5-HT), and γ-aminobutyric acid (GABA). Transgenic zebrafish Tg(huc:EGFP) fluorescence assays revealed that PS-COOH (0.1–100 μg·L−1) caused damage to central neurons. These findings indicate that PS-COOH exposure impairs cholinergic, serotonergic, and GABAergic neurotransmission, induces neuronal damage, and exerts neurotoxic effects on zebrafish larvae. This study provides a theoretical basis for assessing the ecological and health risks of modified microplastics.