Key Takeaways & Executive Findings
- •• • Systematic review of 58 studies (2001–2024) confirms significant associations between OP exposure and increased risks of spontaneous abortion, gestational diabetes, preeclampsia, and preterm birth, with effect sizes varying by exposure window and outcome. • • PON1 genotype polymorphisms modulate OP toxicity: individuals with the QQ192 genotype exhibit lower paraoxonase activity, leading to higher accumulation of toxic oxons and increased susceptibility to adverse pregnancy outcomes. • • Proposed mechanisms include oxidative stress (elevated 8-OHdG), systemic inflammation (increased CRP), and disruption of placental gene networks, as evidenced by altered expression of genes involved in steroidogenesis and immune regulation. • • Exposure assessment predominantly relies on urinary dialkyl phosphate metabolites, but variability in timing and metabolite specificity limits comparability; future studies should incorporate repeated measures and PON1 phenotyping to refine risk assessment.
Abstract
Organophosphate pesticides (OPs), the most extensively used insecticides globally, are ubiquitous in environmental matrices and agricultural products, leading to widespread human exposure. This systematic review evaluates the impact of OP exposure on pregnancy complications and adverse birth outcomes, synthesizing evidence from 58 epidemiological studies published between January 2001 and July 2024. Exposure assessment methods, including biomarkers such as urinary dialkyl phosphates, are critically examined. The review finds significant associations between OP exposure and increased risks of spontaneous abortion, gestational diabetes mellitus, gestational hypertension, preeclampsia, preterm birth, and adverse birth outcomes such as low birth weight and reduced head circumference. Potential mechanisms include paraoxonase 1 (PON1) genotype polymorphisms affecting detoxification capacity, oxidative stress, inflammation, metabolic disruption, and altered placental gene networks. The review highlights inconsistencies across studies due to variability in exposure assessment, timing, and population susceptibility. Future research should prioritize longitudinal designs, repeated biomarker measurements, and consideration of PON1 genetic variants to clarify causal relationships and susceptible windows. This comprehensive synthesis provides critical insights for regulatory policies and clinical interventions aimed at mitigating maternal and child health risks from OP exposure.
1. Introduction
Organophosphate pesticides (OPs) account for approximately 33% of global insecticide use, with China alone producing over 300,000 tons annually. Despite their efficacy, less than 1% of applied OPs reach target pests; the remainder contaminates air, soil, and water, leading to ubiquitous human exposure through dietary and environmental routes. Pregnancy represents a critical window of vulnerability, as OPs can cross the placental barrier and interfere with fetal development. However, existing epidemiological evidence has been fragmented, with inconsistent findings across studies due to heterogeneous exposure assessment and inadequate consideration of genetic susceptibility.
This review systematically synthesizes 58 studies published between January 2001 and July 2024, focusing on the association between OP exposure and key pregnancy complications (spontaneous abortion, gestational diabetes, hypertensive disorders) and adverse birth outcomes (preterm birth, low birth weight). By critically evaluating exposure methodologies and mechanistic pathways—including PON1 genotype variability, oxidative stress, and placental gene dysregulation—this work identifies critical knowledge gaps and proposes a framework for future research. The findings underscore the urgent need for refined risk assessment and targeted interventions to protect maternal and child health in agricultural regions.
Loading authentic research manuscript (Pages 1–5)...
ZHANG Ruixin, ZHUANG Shulin, LIU Jing (2026). Research Progress on the Impact of Organophosphate Pesticide Exposure on Pregnancy Complications and Adverse Birth Outcomes. Environmental Chemistry. https://doi.org/10.7524/j.issn.0254-6108.2025022102
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 primary exposure biomarkers used in the reviewed studies, and how do they correlate with actual OP exposure?
Most studies measured urinary dialkyl phosphate (DAP) metabolites, which reflect cumulative exposure to multiple OPs. However, DAPs are non-specific and can originate from dietary sources, leading to potential misclassification. Some studies used specific metabolites like 3,5,6-trichloro-2-pyridinol (TCPy) for chlorpyrifos, offering higher specificity. Correlations with maternal blood or cord blood OP levels are moderate, and timing of sample collection (e.g., first vs. third trimester) influences associations.
How does PON1 genotype influence the risk of OP-induced pregnancy complications?
PON1 detoxifies toxic OP oxons. The Q192R polymorphism affects catalytic efficiency: the R allele hydrolyzes paraoxon faster but is less efficient for diazoxon and chlorpyrifos-oxon. Studies indicate that women with the QQ genotype (low activity) have higher OP body burdens and increased risk of preterm birth and gestational diabetes, especially when exposed to chlorpyrifos. This gene-environment interaction underscores the need for genotype-stratified risk assessments.
What are the proposed biological mechanisms linking OP exposure to adverse pregnancy outcomes?
Mechanisms include: (1) oxidative stress, evidenced by increased 8-hydroxy-2'-deoxyguanosine (8-OHdG) and lipid peroxidation; (2) systemic inflammation, with elevated C-reactive protein (CRP) and pro-inflammatory cytokines; (3) endocrine disruption, affecting thyroid and sex hormone pathways; and (4) epigenetic changes in placental genes, such as altered DNA methylation of genes involved in nutrient transport and immune modulation. These pathways may act synergistically to impair placentation and fetal growth.
What are the main limitations of the current evidence base, and how can future studies address them?
Key limitations include: (1) cross-sectional designs with single exposure measurements, which may miss critical windows; (2) reliance on self-reported pesticide use in some studies, introducing recall bias; (3) small sample sizes for specific outcomes like preeclampsia; and (4) lack of adjustment for co-exposures. Future studies should employ prospective cohorts with repeated biomarker sampling, incorporate PON1 genotyping, and use mixture models to assess cumulative risk. Additionally, mechanistic studies using placental tissue or organoids are needed to confirm causal pathways.
What are the practical implications for clinical practice and regulatory policy?
For clinicians, screening pregnant women for high OP exposure (e.g., agricultural workers) and identifying PON1 QQ genotype could enable targeted counseling and monitoring. For regulators, the evidence supports stricter limits on OP residues in food and water, and promotion of safer alternatives. The review emphasizes the need for biomonitoring programs in high-risk regions and public health interventions to reduce exposure during pregnancy.
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.