Effects of low doses of bisphenol A on the metabolome of perinatally exposed CD-1 mice

Nicolas J. Cabaton (1) , Cécile Canlet (2) , Perinaaz R. Wadia (3) , Marie Tremblay-Franco (2) , Roselyne Gautier (2) , Jerome Molina (4) , Carlos Sonnenschein (3) , Jean Pierre J. P. Cravedi (4) , Beverly S. Rubin (3) , Ana Soto (3) , Daniel Zalko (1)

1 ToxAlim-MeX - Métabolisme et Xénobiotiques
2 E20 - MetaToul AXIOM
3 Department of Anatomy and Cellular Biology
4 ToxAlim - ToxAlim

BACKGROUND: Bisphenol A (BPA) is a well-known endocrine disruptor used to manufacture polycarbonate plastics and epoxy resins. Exposure of pregnant rodents to low doses of BPA results in pleiotropic effects in their offspring. OBJECTIVE: We used metabolomics-a method for determining metabolic changes in response to nutritional, pharmacological, or toxic stimuli-to examine metabolic shifts induced in vivo by perinatal exposure to low doses of BPA in CD-1 mice. METHODS: Male offspring born to pregnant CD-1 mice that were exposed to vehicle or to 0.025, 0.25, or 25 mu g BPA/kg body weight/day, from gestation day 8 through day 16 of lactation, were examined on postnatal day (PND) 2 or PND21. Aqueous extracts of newborns (PND2, whole animal) and of livers, brains, and serum samples from PND21 pups were submitted to H-1 nuclear magnetic resonance spectroscopy. Data were analyzed using partial least squares discriminant analysis. RESULTS: Examination of endogenous metabolic fingerprints revealed remarkable discrimination in whole extracts of the four PND2 newborn treatment groups, strongly suggesting changes in the global metabolism. Furthermore, statistical analyses of liver, serum, and brain samples collected on PND21 successfully discriminated among treatment groups. Variations in glucose, pyruvate, some amino acids, and neuro-transmitters (gamma-aminobutyric acid and glutamate) were identified. CONCLUSIONS: Low doses of BPA disrupt global metabolism, including energy metabolism and brain function, in perinatally exposed CD-1 mouse pups. Metabolomics can be used to highlight the effects of low doses of endocrine disruptors by linking perinatal exposure to changes in global metabolism.

Mots clés: bisphenol a; endocrine disruptor; fetal origins of adult disease; low dose; nmr fingerprints; partial least squares discriminant analysis; perinatal exposure

Mots clés: metabolomics; metabonomics; toxicology

Domaines: Sciences du Vivant [q-bio]

Nicolas J. Cabaton, Cécile Canlet, Perinaaz R. Wadia, Marie Tremblay-Franco, Roselyne Gautier, et al.. Effects of low doses of bisphenol A on the metabolome of perinatally exposed CD-1 mice. Environmental Health Perspectives, 2013, 121 (5), pp.586-593. ⟨10.1289/ehp.1205588⟩. ⟨hal-02646392⟩