Developmental and metabolic brain alterations in rats exposed to bisphenol A during gestation and lactation.
In recent years, considerable research has focused on the biological effect of endocrine-disrupting chemicals. Bisphenol A (BPA) has been implicated as an endocrine-disrupting chemical (EDC) due to its ability to mimic the action of endogenous estrogenic hormones. The aim of this study was to assess the effect of perinatal exposure to BPA on cerebral structural development and metabolism after birth. BPA (1mg/l) was administered in the drinking water of pregnant dams from day 6 of gestation until pup weaning. At postnatal day 20, in vivo metabolite concentrations in the rat pup hippocampus were measured using high field proton magnetic resonance spectroscopy. Further, brain was assessed histologically for growth, gross morphology, glial and neuronal development and extent of myelination. Localized proton magnetic resonance spectroscopy ((1)H MRS) showed in the BPA-exposed rat a significant increase in glutamate concentration in the hippocampus as well as in the Glu/Asp ratio. Interestingly these two metabolites are metabolically linked together in the malate-aspartate metabolic shuttle. Quantitative histological analysis revealed that the density of NeuN-positive neurons in the hippocampus was decreased in the BPA-treated offspring when compared to controls. Conversely, the density of GFAP-positive astrocytes in the cingulum was increased in BPA-treated offspring. In conclusion, exposure to low-dose BPA during gestation and lactation leads to significant changes in the Glu/Asp ratio in the hippocampus, which may reflect impaired mitochondrial function and also result in neuronal and glial developmental alterations.
Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Nicolas
N
Kunz
Emily Jane
EJ
Camm
Emmanuel
E
Somm
Gregory
G
Lodygensky
Stéphanie
S
Darbre
Michel Lucien
ML
Aubert
Petra Susan
PS
Hüppi
Stéphane Vladimir
SV
Sizonenko
Rolf
R
Gruetter
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001559:Benzhydryl Compounds; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007774:Lactation / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098826:Bisphenol A Compounds
D001224:Aspartic Acid; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D018698:Glutamic Acid; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds