Consequences of perinatal bisphenol A exposure in a mouse model of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a complex disease influenced by genetic and environmental contributing factors. Endocrine disrupting compounds (EDCs) such as bisphenol A (BPA) affect gene expression and hormone-regulated systems throughout the body. We investigated the effects of BPA on Theiler's-virus induced demyelination (TVID), a mouse model of MS. Perinatal BPA exposure, combined with viral infection, resulted in a decreased level of viral antibodies, accelerated the onset of TVID symptoms, increased inflammation in both the spinal cord and digestive tract, and amplified immune-related gene expression changes induced by viral infection. These results demonstrate the effect of BPA on the trajectory of TVID, and illustrate how multiple factors collectively influence autoimmune disease.

Gestational bisphenol-A exposure lowers the threshold for autoimmunity in a model of multiple sclerosis

“…We note a corroborative report that SJL mice exposed to BPA during gestation and through the mother's milk during lactation had accelerated onset of clinical signs after infection at 4 wk of age with Theiler's virus, which produces CNS inflammation (38). At 20 wk postinfection, the degree of inflammation in the spinal cord was higher in BPA-exposed compared with vehicle treatment; no sex differences in the degree of inflammation were noted in the BPA mice.…”

Environmental exposures during pregnancy: Mechanistic effects on immunity

“…However, (intracellular) molecular pathways often remain unknown. Many of the prenatal environmental exposures were linked to multiple different immunomodulatory outcomes and disease types. For example, BPA is associated with immunosuppression and increased infections (Menard et al, ) but has also been implicated in autoimmune diseases such as multiple sclerosis (Brinkmeyer‐Langford et al, ) and Type 1 diabetes (Bodin et al, ), and has even been associated with neuroinflammation and anxiety‐like behavior (Luo et al, ). These findings highlight the complexity of the immune system, which can be affected differently by organ, cell type, and molecular pathway.…”

“…Similar ambiguity exists for prenatal exposure to BPA. Previous discussed studies have associated prenatal BPA with autoimmunity (Bodin et al, ; Brinkmeyer‐Langford et al, ) as well as immunosuppression and increased infections (Menard et al, ). However, yet another animal study showed that prenatal exposure to BPA was dose dependently linked to a decrease in Treg cell populations (Yan, Takamoto, & Sugane, ).…”

“…Besides the fact that prenatal BPA has been associated with immunosuppressive effects, claims have been made to link prenatal BPA exposure to increased risk of multiple sclerosis, an autoimmune disorder involving degradation of myelin nerve sheaths. In a mouse model of multiple sclerosis (Theiler's virus induced demyelination), prenatal and postnatal exposure to BPA accelerated the onset of autoimmune symptoms like limb weakness, wobbly gait, and slowed righting reflex, reduced antiviral antibodies, and increased spinal cord inflammation (Brinkmeyer‐Langford et al, ). However, Krementsov et al () assert that gestational exposure to BPA did not alter two models of EAE.…”

Epigenetic underpinnings of developmental immunotoxicity and autoimmune disease

“…Diabetic (NOD) mice given BPA during gestation generated female offspring with an increased incidence of diabetes [39]. Perinatal BPA exposure accelerated inflammation in a mouse model of virally-induced multiple sclerosis [40]. …”