TY - JOUR
TI - Long term transcriptional and behavioral effects in mice developmentally exposed to a mixture of endocrine disruptors associated with delayed human neurodevelopment
AU - Repouskou, A.
AU - Papadopoulou, A.-K.
AU - Panagiotidou, E.
AU - Trichas, P.
AU - Lindh, C.
AU - Bergman, Å.
AU - Gennings, C.
AU - Bornehag, C.-G.
AU - Rüegg, J.
AU - Kitraki, E.
AU - Stamatakis, A.
JO - Scientific Reports
PY - 2020
VL - 10
TODO - 1
SP - null
PB - Institute of Geographic Sciences and Natural Resources Research
SN - 2045-2322
TODO - 10.1038/s41598-020-66379-x
TODO - endocrine disruptor;  hormone;  transcriptome, adrenal gland;  animal;  animal behavior;  brain;  drug effect;  female;  genetic transcription;  growth, development and aging;  male;  metabolism;  organ size;  pollutant;  toxicity, Adrenal Glands;  Animals;  Behavior, Animal;  Brain;  Endocrine Disruptors;  Environmental Pollutants;  Female;  Hormones;  Male;  Organ Size;  Transcription, Genetic;  Transcriptome
TODO - Accumulating evidence suggests that gestational exposure to endocrine disrupting chemicals (EDCs) may interfere with normal brain development and predispose for later dysfunctions. The current study focuses on the exposure impact of mixtures of EDCs that better mimics the real-life situation. We herein describe a mixture of phthalates, pesticides and bisphenol A (mixture N1) detected in pregnant women of the SELMA cohort and associated with language delay in their children. To study the long-term impact of developmental exposure to N1 on brain physiology and behavior we administered this mixture to mice throughout gestation at doses 0×, 0.5×, 10×, 100× and 500× the geometric mean of SELMA mothers’ concentrations, and examined their offspring in adulthood. Mixture N1 exposure increased active coping during swimming stress in both sexes, increased locomotion and reduced social interaction in male progeny. The expression of corticosterone receptors, their regulator Fkbp5, corticotropin releasing hormone and its receptor, oxytocin and its receptor, estrogen receptor beta, serotonin receptors (Htr1a, Htr2a) and glutamate receptor subunit Grin2b, were modified in the limbic system of adult animals, in a region-specific, sexually-dimorphic and experience-dependent manner. Principal component analysis revealed gene clusters associated with the observed behavioral responses, mostly related to the stress axis. This integration of epidemiology-based data with an experimental model increases the evidence that prenatal exposure to EDC mixtures impacts later life brain functions. © 2020, The Author(s).
ER -