Application of the adverse outcome pathway to identify molecular changes in prenatal brain programming induced by IUGR: Discoveries after EGCG exposure

• DOI: 10.1016/j.fct.2022.113506
• Publication Date: 2022-11-10T04:37:02Z
• Authors: Britta Anna Kühne; Elisabet Teixidó; Miren Ettcheto; Teresa Puig; Marta Planas; Lidia Feliu; Laura Pla; Victoria Campuzano; Eduard Gratacós; Ellen Fritsche; Miriam Illa; Marta Barenys
• Keywords: 0303 health sciences; Fetal Growth Retardation; Adverse Outcome Pathways; Medicina prenatal; Neurogenesis; Brain; Fetal growth; Catechin; Rats; 3. Good health; Mice; 03 medical and health sciences; Neural Stem Cells; Pregnancy; Prenatal medicine; Humans; Animals; Female; Rabbits; Neurogenètica; Neurogenetics; Creixement fetal

Following a multi-disciplinary approach integrating information from several experimental models we have collected new evidence supporting, expanding and redesigning the AOP "Disrupted laminin/int-β1 interaction leading to decreased cognitive function". Investigations in vitro in rabbit and rat neurospheres and in vivo in mice exposed to EGCG (epigallocatechin-gallate) during neurodevelopment are combined with in vitro evaluations in neural progenitor cells overexpressing int-β1 and literature information from int-β1 deficiency models. We have discovered for the first time that neural progenitor cells from intrauterine growth restricted (IUGR) animals overexpress int-β1 at gene and protein level and due to this change in prenatal brain programming they respond differently than control neurospheres to the exposure of EGCG, a compound triggering neural progenitor cell migration alterations. We have also identified that EGCG developmental exposure has deleterious effects on neuronal branching and arborization in vitro and in vivo. Our results warn that a thorough developmental neurotoxicity characterization of this and other catechin-based food supplements is needed before recommending their consumption during pregnancy.