Effects of Low Doses of Bisphenol A on the Metabolome of Perinatally Exposed CD-1 Mice

Abstract

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 µg 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 1H 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 neurotransmitters (γ-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.

Bisphenol A Impairs Synaptic Plasticity by Both Pre‐ and Postsynaptic Mechanisms

“…These alterations provide the presynaptic mechanism of impaired LTP by BPA exposure. The above findings corroborate previous researches showing that perinatal BPA exposure results in less glutamate release from presynaptic neurons 32. Therefore, the presynaptic site in the hippocampus is susceptible to both perinatal and juvenile BPA exposure.…”

Delayed Neuroendocrine Sexual Maturation in Female Rats After a Very Low Dose of Bisphenol A Through Altered GABAergic Neurotransmission and Opposing Effects of a High Dose

“…GABAergic tone appeared to be increased after BPA exposure in some studies (34,37) or reduced in others (36,38,39). In a recent study close to our conditions using whole brain extracts from animals exposed to different doses of BPA from gestational day 8 to PND16, Cabaton et al (36), investigated brain composition by nuclear magnetic resonance spectroscopy on PND21. In this non targeted metabolomics study, these authors reported that 25 g/kg⅐d of BPA could reduce GABA concentrations in the brain.…”

Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): Evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation

“…Developmental exposure to these endocrine disrupting chemicals (EDCs) can result in a permanent change in the regulation of insulin and glucose levels [2]. EDCs may also impact metabolism through effects on the neuroendocrine systems that control feeding as well as other behaviors [7–9]. Importantly, some neural and metabolic effects due to fetal exposure to EDCs are observed during specific periods during postnatal life, such as during early adolescence [10], adulthood [11] or middle age [12].…”