Systems Biology and CBMN-cyt Reveal Transplacental Genotoxicity of Pesticide Mixtures in an Agricultural Region of Colombia

Background:Prenatal exposure to pesticide mixtures is a growing public health concern, particularly in regions where agricultural activity is intense. These mixtures may interfere with fetal development through various pathways. Yet, few studies have examined their combined effects in real-world contexts. Methods:An in-silico network analysis was conducted using STITCH and Cytoscape to model interactions between Paraquat, Chlorpyrifos, Cypermethrin, and Dieldrin with human proteins. Hub genes and enriched biological processes were identified. Predicted disruptions were evaluated in 86 pregnant women and their newborns using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay. A sensitivity analysis was performed to assess the impact of potential exposure misclassification. Results:Key regulatory nodes (CASP3, MAPK1, CYP3A4, ESR1) and pathways related to placental development, oxidative stress, and apoptosis were identified as plausible hypotheses. Exposed dyads showed significantly elevated frequencies of micronuclei and nuclear buds. Moderate but significant maternal–neonatal correlations were found for necrosis (ρ = 0.45) and apoptosis (ρ = 0.41), suggesting a coordinated biological response. Regression models confirmed higher genomic instability in exposed individuals. A non-linear dose-response pattern was observed, potentially indicating cytotoxicity at higher exposure levels. Conclusions: Our findings support the hypothesis that prenatal exposure to pesticide mixtures is associated with molecular alterations and cytogenetic damage in both mothers and newborns. Integrating bioinformatics with biomonitoring is a valuable approach to uncover early biological signals of environmental risk. The CBMN-cyt assay shows promise for maternal health surveillance in vulnerable agricultural populations.