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Fetal exposure to bisphenol A as a risk factor for the development of childhood asthma: an animal model study.

Nakajima Y, Goldblum RM, Midoro-Horiuti T - Environ Health (2012)

Bottom Line: We have focused on the potential effects of bisphenol A (BPA), a chemical pollutant with one of the largest productions, on the development of childhood asthma.Prenatal exposures that produce environmentally relevant burdens of BPA, followed by postnatal allergic sensitization and challenges, promote the development of experimental allergic asthma.Delayed expression of BPA-metabolizing enzymes may explain, at least in part, the enhanced fetal susceptibility to this common environmental contaminant.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departments of Pediatrics and Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0366, USA.

ABSTRACT

Background: The prevalence of asthma in industrialized countries has been increasing dramatically and asthma is now the most common chronic disease of children in the United States. The rapidity of the increase strongly suggests that changes in environmental exposures are the likely cause of this epidemic. Further, the early onset of allergic manifestations suggests that these exposures may act on the prenatal development of the immune system. We have focused on the potential effects of bisphenol A (BPA), a chemical pollutant with one of the largest productions, on the development of childhood asthma. We have reported that perinatal BPA exposure promotes the development of allergic asthma in a mouse model. The current study was designed to identify a critical period of BPA exposure and to begin elucidating the mechanisms for this susceptibility.

Methods: Female BALB/c mice received 10 micro g/ml BPA in their drinking water from one week before pregnancy until the end of the study. Some of the pups were transferred in the first 48 h of life from their BPA-loaded mother to an unexposed mother, or vice versa. Half of the pups were sensitized with a low dose of the experimental allergen ovalbumin (OVA), the rest received PBS as an unsensitized controls. On day 22, the pups were challenged by inhalations of ovalbumin or PBS followed by quantification of eosinophils in and hyperreactivity of their airways, major indicators of experimental asthma in this classical mouse model. Hepatic expression of two isoforms of UDP-glucuronosyltransferase (Ugt) was quantified by quantitative RT-PCR at various ages.

Results: Pups exposed to BPA in utero and through breast milk, or in utero only, displayed an asthma phenotype in response to their "suboptimal" allergic sensitization, whereas, pups only exposed to BPA postnatally from breast milk, did not. The expression of Ugt2b1, an isoform related to BPA clearance in rats, was not detectable in mouse fetuses and newborn pups, but increased by day 5 and approached adult levels by day 25.

Conclusions: Prenatal exposures that produce environmentally relevant burdens of BPA, followed by postnatal allergic sensitization and challenges, promote the development of experimental allergic asthma. Delayed expression of BPA-metabolizing enzymes may explain, at least in part, the enhanced fetal susceptibility to this common environmental contaminant.

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Related in: MedlinePlus

BPA effects on OVA induced airway inflammation. Eosinophil counts in BAL fluid 18 days after i.p. injection of OVA. Bars indicate the mean ± SE for groups. N = 4-9 litters. *p = 0.03 and **p < 0.01 compared with OVA-sensitized pups from non BPA exposed mothers. *** The eosinophil number in one BAL fluid was 5SE greater than the mean of the other samples. It was considered an outlier and not included in the statistics. There was no significant difference between any of the non OVA-sensitized groups
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Figure 3: BPA effects on OVA induced airway inflammation. Eosinophil counts in BAL fluid 18 days after i.p. injection of OVA. Bars indicate the mean ± SE for groups. N = 4-9 litters. *p = 0.03 and **p < 0.01 compared with OVA-sensitized pups from non BPA exposed mothers. *** The eosinophil number in one BAL fluid was 5SE greater than the mean of the other samples. It was considered an outlier and not included in the statistics. There was no significant difference between any of the non OVA-sensitized groups

Mentions: To determine whether BPA alters allergen-induced pulmonary inflammation, we quantified total cells and eosinophils in BAL fluid. We observed a significant increase in eosinophils in BAL fluids from OVA sensitized pups exposed to BPA only in utero, p = 0.03 vs. non BPA exposed group and those exposed in utero and postnatal BPA, p < 0.01 vs. the non BPA exposed group (Figure 3). There were no significant differences in total cell numbers between any groups.


Fetal exposure to bisphenol A as a risk factor for the development of childhood asthma: an animal model study.

Nakajima Y, Goldblum RM, Midoro-Horiuti T - Environ Health (2012)

BPA effects on OVA induced airway inflammation. Eosinophil counts in BAL fluid 18 days after i.p. injection of OVA. Bars indicate the mean ± SE for groups. N = 4-9 litters. *p = 0.03 and **p < 0.01 compared with OVA-sensitized pups from non BPA exposed mothers. *** The eosinophil number in one BAL fluid was 5SE greater than the mean of the other samples. It was considered an outlier and not included in the statistics. There was no significant difference between any of the non OVA-sensitized groups
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3306825&req=5

Figure 3: BPA effects on OVA induced airway inflammation. Eosinophil counts in BAL fluid 18 days after i.p. injection of OVA. Bars indicate the mean ± SE for groups. N = 4-9 litters. *p = 0.03 and **p < 0.01 compared with OVA-sensitized pups from non BPA exposed mothers. *** The eosinophil number in one BAL fluid was 5SE greater than the mean of the other samples. It was considered an outlier and not included in the statistics. There was no significant difference between any of the non OVA-sensitized groups
Mentions: To determine whether BPA alters allergen-induced pulmonary inflammation, we quantified total cells and eosinophils in BAL fluid. We observed a significant increase in eosinophils in BAL fluids from OVA sensitized pups exposed to BPA only in utero, p = 0.03 vs. non BPA exposed group and those exposed in utero and postnatal BPA, p < 0.01 vs. the non BPA exposed group (Figure 3). There were no significant differences in total cell numbers between any groups.

Bottom Line: We have focused on the potential effects of bisphenol A (BPA), a chemical pollutant with one of the largest productions, on the development of childhood asthma.Prenatal exposures that produce environmentally relevant burdens of BPA, followed by postnatal allergic sensitization and challenges, promote the development of experimental allergic asthma.Delayed expression of BPA-metabolizing enzymes may explain, at least in part, the enhanced fetal susceptibility to this common environmental contaminant.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departments of Pediatrics and Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0366, USA.

ABSTRACT

Background: The prevalence of asthma in industrialized countries has been increasing dramatically and asthma is now the most common chronic disease of children in the United States. The rapidity of the increase strongly suggests that changes in environmental exposures are the likely cause of this epidemic. Further, the early onset of allergic manifestations suggests that these exposures may act on the prenatal development of the immune system. We have focused on the potential effects of bisphenol A (BPA), a chemical pollutant with one of the largest productions, on the development of childhood asthma. We have reported that perinatal BPA exposure promotes the development of allergic asthma in a mouse model. The current study was designed to identify a critical period of BPA exposure and to begin elucidating the mechanisms for this susceptibility.

Methods: Female BALB/c mice received 10 micro g/ml BPA in their drinking water from one week before pregnancy until the end of the study. Some of the pups were transferred in the first 48 h of life from their BPA-loaded mother to an unexposed mother, or vice versa. Half of the pups were sensitized with a low dose of the experimental allergen ovalbumin (OVA), the rest received PBS as an unsensitized controls. On day 22, the pups were challenged by inhalations of ovalbumin or PBS followed by quantification of eosinophils in and hyperreactivity of their airways, major indicators of experimental asthma in this classical mouse model. Hepatic expression of two isoforms of UDP-glucuronosyltransferase (Ugt) was quantified by quantitative RT-PCR at various ages.

Results: Pups exposed to BPA in utero and through breast milk, or in utero only, displayed an asthma phenotype in response to their "suboptimal" allergic sensitization, whereas, pups only exposed to BPA postnatally from breast milk, did not. The expression of Ugt2b1, an isoform related to BPA clearance in rats, was not detectable in mouse fetuses and newborn pups, but increased by day 5 and approached adult levels by day 25.

Conclusions: Prenatal exposures that produce environmentally relevant burdens of BPA, followed by postnatal allergic sensitization and challenges, promote the development of experimental allergic asthma. Delayed expression of BPA-metabolizing enzymes may explain, at least in part, the enhanced fetal susceptibility to this common environmental contaminant.

Show MeSH
Related in: MedlinePlus