Toxic effects of perinatal maternal exposure to nonylphenol on lung inflammation in male offspring rats

Abstract

The incidence of asthma and its related allergic diseases has increased dramatically over the last decade. Asthma is a complex disease caused by genetic and environmental factors. Nonylphenol (NP), a typical endocrine disrupting chemical (EDC), is a major current focus in asthma research. Pregnant Sprague-Dawley rats (n = 8–10 per group) were given a consecutive daily dose of NP (25, 50, or 100 mg/kg/day) or an equivalent volume of vehicle by gavage from gestational day 7 until postnatal day (PND) 21. Exposure to 100 mg/kg NP increased the body mass of the offspring on PND 43. Perinatal exposure to NP in maternal rats led to a dose-dependent increase of NP level in the lung tissue of the offspring. The numbers of lymphocytes and neutrophils in bronchoalveolar lavage fluid were significantly higher in the 100 mg/kg NP group than those in the control. Histopathological examination of the lung showed that exposure to high dose NP resulted in a slightly thickened bronchiolar smooth muscles with inflammatory cell infiltration. In the cytoplasm of type II epithelial cells, osmiophilic lamellar bodies were observed, with emptied lamellar bodies. NP significantly increased the expressions of high mobility group box 1 protein (HMGB1) mRNA and nuclear factor κB (NF-κB) mRNA in the lung tissue of the offspring in a dose dependent manner. Similarly, the expressions of HMGB1, NF-κBp65 and estrogen receptor-β (ER-β) proteins increased with an increase of NP dose. NP content was positively correlated with the expressions of HMGB1 and NF-κB mRNA as well as HMGB1, NF-κBp65, and ER-β proteins in the lung tissue of offspring. Perinatal exposure to NP from the maternal rats might induce airway inflammation in the offspring, which may be due to NP-induced infiltration of inflammatory cells into the airway, and pathological alterations in airway structure as well as abnormal expression patterns of inflammation-related genes, proteins (including HMGB1 and NF-κB) and estrogen receptor β.