Metabolic targets of endocrine disrupting chemicals assessed by cord blood transcriptome profiling

Abstract

Early life exposure to endocrine disrupting chemicals (EDCs) has been frequently associated with impaired perinatal growth, an important risk factor for later onset of metabolic disorders. We analyzed whether the cord blood transcriptome showed early indications of alterations in metabolic processes in 195 human samples in relation to cord blood levels of dichlorodiphenyldichloroethylene (p,p'-DDE), polychlorinated biphenyl-153 (PCB-153), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS). Overall, 39 metabolically relevant transcription factors were significantly enriched (31 by p,p'-DDE, 10 by PCB-153, 8 by PFOA, and 2 by PFOS). These included the glucocorticoid receptor (p,p'-DDE and PCB-153) and the progesterone receptor (PFOA and PFOS). The 'insulin receptor signaling', 'acute phase response signaling', 'Interleukin(IL)-6 signaling', and 'prolactin signaling' pathways were significantly enriched in relation to p,p'-DDE. Transcriptional changes at birth suggest a role for specific metabolic targets as a link between prenatal EDC exposure and metabolic disorders later in life.

Keywords: Birth cohort; Cord blood; Endocrine disrupting chemicals; Glucocorticoid receptor; Metabolic disorders; Transcriptomics.