Maternal bisphenol a exposure promotes the development of experimental asthma in mouse pups

Abstract

Background: We recently reported that various environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators in vitro.

Objectives: We hypothesized that environmental estrogens would enhance allergic sensitization as well as bronchial inflammation and responsiveness. To test this hypothesis, we exposed fetal and neonatal mice to the common environmental estrogen bisphenol A (BPA) via maternal loading and assessed the pups' response to allergic sensitization and bronchial challenge.

Methods: Female BALB/c mice received 10 microg/mL BPA in their drinking water from 1 week before impregnation to the end of the study. Neonatal mice were given a single 5 microg intraperitoneal dose of ovalbumin (OVA) with aluminum hydroxide on postnatal day 4 and 3% OVA by nebulization for 10 min on days 13, 14, and 15. Forty-eight hours after the last nebulization, we assessed serum IgE antibodies to OVA by enzyme-linked immunosorbent assay (ELISA) and airway inflammation and hyperresponsiveness by enumerating eosinophils in bronchoalveolar lavage fluid, whole-body barometric plethysmography, and a forced oscillation technique.

Results: Neonates from BPA-exposed mothers responded to this "suboptimal" sensitization with higher serum IgE anti-OVA concentrations compared with those from unexposed mothers (p < 0.05), and eosinophilic inflammation in their airways was significantly greater. Airway responsiveness of the OVA-sensitized neonates from BPA-treated mothers was enhanced compared with those from unexposed mothers (p < 0.05).

Conclusions: Perinatal exposure to BPA enhances allergic sensitization and bronchial inflammation and responsiveness in a susceptible animal model of asthma.

Figure 1

BPA effects on AHR after methacholine challenge. The lung function of the pups was analyzed by (A) whole-body barometric plethysmograph on PND17 (challenged with 0, 1,10, 25, or 50 mg/mL methacholine) or (B) forced oscillation analysis on PND22 (challenged with 0, 0.1, 1, 10, 30, or 50 mg/mL methacholine). R, lung resistance. Data are mean ± SE (n = 7–11). Analysis was performed on pups from 4–6 mothers and divided into OVA and sham immunization groups. *p < 0.05 compared with all other groups after 25 mg/mL and 50 mg/mL methacholine by whole-body barometric plethysmograph and after 30 mg/mL by the forced oscillation analysis.

Figure 2

BPA effects on OVA hypersensitivity. Total cell number (A) and eosinophil counts (B) in BAL fluid 13 days after ip injection with OVA or PBS. The result for each pup is shown as an individual point (n = 12–16 pups from 6–7 mothers per group), and the bars indicate the mean ± 1 SE for groups. *p < 0.05 compared with all other groups.

Figure 3

BPA effects on allergen-specific IgE production. IgE anti-OVA concentrations in sera were measured by ELISA. The result for each pup is shown as an individual point (n = 12–16 pups from 6–7 mothers per group), and the bars indicate mean ± 1 SE for groups. The detection limit was 0.05 ng/mL. *p < 0.05 compared with all other groups.