Chronic toxicogenomic and epigenetic evaluation of endocrine disruption in animal-derived reproductive and hypothalamic organoids co-exposed to plastic-associated toxicants (Nonylphenol and PFOS)

The Mechanism4EPT project investigates the chronic endocrine and neurodevelopmental effects of co-exposure to plastic-associated toxicants Nonylphenol (NP) and perfluorooctane sulfonate (PFOS), using advanced 3D organoid models derived from albino rat reproductive and hypothalamic tissues. These models better replicate in vivo tissue complexity compared to traditional 2D cultures, enabling realistic simulation of chronic co-exposure scenarios. The project aims to: (i) delineate dose- and time-dependent toxicogenomic responses, (ii) map epigenetic modifications such as DNA methylation and histone changes, (iii) uncover disrupted neuroendocrine molecular pathways, and (iv) identify heritable epigenetic markers in progeny organoid cells that indicate cellular memory of toxicant exposure. Multi-omics approaches including RNA-seq, ATAC-seq, and bisulfite sequencing, integrated with AI-driven bioinformatics, will generate comprehensive mechanistic insights into combined NP and PFOS toxicity. This research directly supports the EU’s Chemicals Strategy for Sustainability by informing safer chemical regulation and enhancing alternatives to animal testing, in alignment with the EU Green Deal and Sustainable Development Goals on health and responsible production. The project incorporates an intersectoral secondment at Altomics Datamation Ltd., facilitating translational risk assessment and industrial AI applications. Outputs will include novel organoid models and predictive AI pipelines with strong potential for regulatory adoption. Ultimately, Mechanism4EPT seeks to advance understanding of chronic endocrine disruption by plastic contaminants, fostering improved public health protection and sustainable environmental stewardship.