Machine Learning Reveals Common Transcriptomic Signature Across Brain and Placenta Following Developmental Organophosphate Ester Exposure

Purpose: Identify gene expression changes in hippocampus of postnatal day 10 pups whose mothers were exposed to OPFRs during pregnancy (3.3 mg/kg) compared to unexposed controls. Determine if developmental OPFR exposure influences common genes or gene pathways across multiple tissues and developmental time pionts. Methods: One new RNAseq data set (hippocampus) generated for this study and two extant RNAseq data sets (placenta and cortex) were reanalyzed with a validated machine learning methodology and traditional bioinformatics techniques. Results of differentially expressed genes were compared across tissues and the submitted to pathway analysis. Results: OPFR effects on gene expression are sex specific, with limited changes in male hippocampus and significant enrichment of genes related to voltage gated ion channels in females. Cross tissue analysis of OPFR exposured P1 cortex and placenta demonstrated common genes identified in each tissue related to mitochondria physiology Conclusions: Developmental OPFR exposure results in gene expression changes in hippocampus, cortex, and placenta related to proteins underlying mitochondria physiology, particularly oxidative phosphorylation and electron transport chain. These findings support the growing concerns that developmental OPFR exposure may contribute to the etiology of neurodevelopmental disorders. Overall design: Maternal OPFR exposed mRNA profiles from dorsal hippocampus of 10-day old rats