Background: The prevalence of asthma in industrialized countries has been increasing dramatically and asthma is\r\nnow the most common chronic disease of children in the United States. The rapidity of the increase strongly\r\nsuggests that changes in environmental exposures are the likely cause of this epidemic. Further, the early onset of\r\nallergic manifestations suggests that these exposures may act on the prenatal development of the immune system.\r\nWe have focused on the potential effects of bisphenol A (BPA), a chemical pollutant with one of the largest\r\nproductions, on the development of childhood asthma. We have reported that perinatal BPA exposure promotes\r\nthe development of allergic asthma in a mouse model. The current study was designed to identify a critical period\r\nof BPA exposure and to begin elucidating the mechanisms for this susceptibility.\r\nMethods: Female BALB/c mice received 10 micro g/ml BPA in their drinking water from one week before\r\npregnancy until the end of the study. Some of the pups were transferred in the first 48 h of life from their BPAloaded\r\nmother to an unexposed mother, or vice versa. Half of the pups were sensitized with a low dose of the\r\nexperimental allergen ovalbumin (OVA), the rest received PBS as an unsensitized controls. On day 22, the pups\r\nwere challenged by inhalations of ovalbumin or PBS followed by quantification of eosinophils in and\r\nhyperreactivity of their airways, major indicators of experimental asthma in this classical mouse model. Hepatic\r\nexpression of two isoforms of UDP-glucuronosyltransferase (Ugt) was quantified by quantitative RT-PCR at various\r\nages.\r\nResults: Pups exposed to BPA in utero and through breast milk, or in utero only, displayed an asthma phenotype\r\nin response to their ââ?¬Å?suboptimalââ?¬Â allergic sensitization, whereas, pups only exposed to BPA postnatally from breast\r\nmilk, did not. The expression of Ugt2b1, an isoform related to BPA clearance in rats, was not detectable in mouse\r\nfetuses and newborn pups, but increased by day 5 and approached adult levels by day 25.\r\nConclusions: Prenatal exposures that produce environmentally relevant burdens of BPA, followed by postnatal\r\nallergic sensitization and challenges, promote the development of experimental allergic asthma. Delayed\r\nexpression of BPA-metabolizing enzymes may explain, at least in part, the enhanced fetal susceptibility to this\r\ncommon environmental contaminant.
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