Effects of BPA and BPS exposure limited to early embryogenesis persist to impair non-associative learning in adults

Abstract

BackgroundBisphenol-A (BPA) is a polymerizing agent used in plastic bottles and several routinely used consumer items. It is classified among endocrine disrupting chemicals suspected to cause adverse health effects in mammals ranging from infertility and cancer to behavioral disorders. Work with the invertebrate lab model Caenorhabditis elegans has shown that BPA affects germ cells by disrupting double-stranded DNA break repair mechanisms. The current study utilizes this model organism to provide insight into low-dose and long-term behavioral effects of BPA and bisphenol-S (BPS), a supposed safer replacement for BPA.FindingsExperiments presented in our report demonstrate that the effects of embryonic exposure to considerably low levels of BPA persist into adulthood, affecting neural functionality as assayed by measuring habituation to mechano-sensory stimuli in C. elegans. These results are noteworthy in that they are based on low-dose exposures, following the rationale that subtler effects that may not be morphologically apparent are likely to be discernible through behavioral changes. In addition, we report that embryonic exposure to BPS follows a pattern similar to BPA.ConclusionsBuilding upon previous observations using the C. elegans model, we have shown that exposure of embryos to BPA and BPS affects their behavior as adults. These long-term effects are in line with recommended alternate low-dose chemical safety testing approaches. Our observation that the effects of BPS are similar to BPA is not unexpected, considering their structural similarity. This, to our knowledge, is the first reported behavioral study on low-dose toxicity of any endocrine disrupting chemical in C. elegans.

Neuroendocrine disruption in animal models due to exposure to bisphenol A analogues

“…Embryonic exposure of C. elegans to BPA or BPS at low doses (spanning 0.1 to 10 μM) results in compromised neural function at adulthood, as determined by exposed individuals requiring higher number of mechano-sensory stimuli in order to habituate to touch [107]. Exposure to varying concentrations of BPA or BPS resulted in decreased number of eggs laid.…”

“…The HPT and hypothalamic-pituitary-gonadal (HPG) axes in zebrafish also appears to be vulnerable to the BPA and BPA-substitute exposure, as indicated by the above studies that tested the chemicals alongside each other [102; 103; 104; 105; 106] and another study that solely examined the effects of BPA on thyroid specific gene expression [108]. Neurosensory function and the brain/gonad also appears to be susceptible to BPA and BPA-analogue exposure in C. elegans [107]. …”

“…Developmental or adult exposure of animal models to BPA-substitutes leads to several behavioral disruptions, including an increase in anxiogenic and hyperactive behaviors, compromised social interactions and parental care ability, and delayed habituation responses [62; 63; 64; 99; 107]. The collective data to date suggests that these chemicals can affect gene expression in the prefrontal cortex, hypothalamus, MPOA region, and likely other brain areas [28; 64; 65; 100; 103; 105].…”

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

“…BPA was demonstrated to impair neural ectoderm specification and neural progenitor cells in mouse embryonic stem cells [83]. In a study using Caenorhabditis elegans to examine early embryogenesis exposure to BPA and BPS into adulthood, it was shown that changes in behavior and learning were followed into adulthood [84]. BPA was shown to decrease the proliferation of multipotent neural progenitor cells and produce cytotoxicity in F1 mice, and in low-doses stimulated neuronal differentiation which might disrupt brain development [85].…”

Fungal Bioremediation of Emerging Micropollutants in Municipal Wastewaters

“…The low-dose, human beings are exposed to, should not be underestimated since it could cause long-term effects as recently demonstrated by Mersha and collaborators (2015). The exposure to low concentration of bisphenol A (BPA) and bisphenol S during embryogenesis altered adulthood behavior causing neural dysfunctioning (Mersha et al 2015). …”