Perinatal bisphenol A exposures increase production of pro-inflammatory mediators in bone marrow-derived mast cells of adult mice

Abstract

Bisphenol A (BPA) is a widely used monomer of polycarbonate plastics and epoxide resin that has been implicated in asthma pathogenesis when exposure occurs to the developing fetus. However, few studies have examined the relationship between perinatal BPA exposure and asthma pathogenesis in adulthood. This study used an isogenic mouse model to examine the influence of perinatal BPA exposure via maternal diet on inflammatory mediators associated with asthma in 6-month-old adult offspring by measuring bone marrow-derived mast cell (BMMC) production of lipid mediators (cysteinyl leukotrienes and prostaglandin D2), cytokines (interleukin [IL]-4, IL-5, IL-6, IL-13, and tumor necrosis factor [TNF]-α), and histamine. Global DNA methylation levels in BMMCs from adult offspring were determined to elucidate a potential regulatory mechanism linking perinatal exposure to mast cell phenotype later in life. Four BPA exposure doses were tested: low (50 ng BPA/kg diet, n = 5), medium (50 μg BPA/kg diet, n = 4), high (50 mg BPA/kg diet, n = 4), and control (n = 3). Following BMMC activation, increases in cysteinyl leukotriene (p < 0.01) and TNFα (p < 0.05) production were observed in all BPA-exposure groups, and increases in prostaglandin D2 (p < 0.01) and IL-13 (p < 0.01) production were observed in the high exposure group. Additionally, BMMCs from adult mice in all exposure groups displayed a decrease in global DNA methylation compared to control animals. Thus, perinatal BPA exposure displayed a long-term influence on mast cell-mediated production of pro-inflammatory mediators associated with asthma and global DNA methylation levels, suggesting a potential for mast cell dysregulation, which could affect pulmonary inflammation associated with allergic airway disease into adulthood.

Early life exposure to bisphenol A investigated in mouse models of airway allergy, food allergy and oral tolerance

“…Perinatal BPA exposure at doses relevant for humans has previously been reported to enhance colonic inflammation in adulthood, determined as neutrophil infiltration, increased IFNg and decreased TGFb, after "chronic" OVA challenges in a rat model of food intolerance (IgG, non-allergic) (Menard et al, 2014b). Further, prenatal BPA exposure was recently reported to affect mast cell-mediated production of pro-inflammatory mediators and decreased DNA methylation in bone marrow mast cells from adult mice (O'Brien et al, 2014b). Taken together, these studies may indicate that perinatal BPA exposure may give longterm effects on the gut-associated lymphoid tissue, but further studies of how BPA doses relevant for human exposure affects the gastrointestinal cells and intestinal microbiome would be useful for elucidating any potential impact on human health.…”

Bisphenol a Exposure, DNA Methylation, and Asthma in Children

“…It has been shown that BPA is a harmful environmental chemical and its exposure may influence the human immune system [8,31]. BPA exposure might affect the immune system by releasing some pro-inflammatory mediators, including cysteinyl leukotriene, MAPK1, prostaglandin D2, and IL-13, which might be related to the development of asthma [32]. In addition, BPA exposure has been shown to affect many human chronic diseases, including diabetes, metabolic syndrome, reproductive disorders, cardiovascular diseases, respiratory diseases, and breast cancer [33].…”

Gene regulation and genetics in neurochemistry, past to future

“…Such a priming toward inflammation has been associated with a decline in global CpG methylation (O'Brien et al . ).…”

“…Tumor necrosis factor is more readily elevated by 6-hydroxydopamine in the substantial nigra of rats that had been exposed to LPS in utero (Ling et al 2004), and microglia generally express more proinflammatory genes when obtained from animals that had been exposed to LPS in utero (Cao et al 2015). Such a priming toward inflammation has been associated with a decline in global CpG methylation (O'Brien et al 2014).…”