期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 170, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2022.113506
关键词
Embryonic and fetal development; Fetal growth restriction (FGR); Progenitor cells; Neurogenesis; Neurosphere model; Epigallocatechin gallate (EGCG); Developmental neurotoxicity (DNT)
资金
- Instituto de Salud Carlos III [PI18/01763]
- European Regional Development Fund, A way to make Europe
- LaCaixa Foundation [LCF/PR/GN14/10270005, LCF/PR/GN18/10310003]
- AGAUR [1531]
- Fundacio Bosch i Gimpera [300155]
Using a multidisciplinary approach, we have collected new evidence supporting and expanding the understanding of the disrupted laminin/int-I31 interaction, which leads to decreased cognitive function. Our study reveals that neural progenitor cells from intrauterine growth restricted (IUGR) animals overexpress int-I31 and respond differently to EGCG exposure, which triggers neural progenitor cell migration alterations. Additionally, we have identified that EGCG has detrimental effects on neuronal branching and arborization.
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-I31 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-I31 and literature information from int-I31 deficiency models. We have discovered for the first time that neural progenitor cells from intrauterine growth restricted (IUGR) animals overexpress int-I31 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.
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