The effects of urban particulate matter on the nasal epithelium by gender: An experimental study in mice.

Nose is the first portion of the respiratory system into contact with air pollution particles, including organic compounds that could act as endocrine releasers. The objective was to identify and quantify estrogenic receptor-ß (ERß), aryl hydrocarbon receptor (AhR), the cytochrome P450 enzymes CYP1A1, 1A2, 1B1, and mucus profile in the nasal epithelium of mice. BALB/c mice male (n = 32) and female (n = 82) in proestrus, estrus and diestrus were divided into two groups: 1) exposed to ambient air; 2) concentrated ambient particles (CAPs) to achieve an accumulated dose (concentration vs. time product) of 600 µg/m(3), the time of the exposure was controlled to ensure the same concentration for all groups (5 days per week for 40-51 days). RT-PCR (Erß-1, Erß-2, Ahr, Cyp1a1, Cyp1a2, Cyp1b1), immunohistochemistry and morphometry (ERß, AhR) were used to analyze. The mucus profiles were examined using acid (Alcian Blue) and neutral (periodic acid Schiff's) stains. Exposed females had significantly lower levels of Erß-2 mRNA than exposed males (p = 0.036). Cyp1b1 mRNA in diestrus females was significantly lower in the CAP-exposed group compared with the ambient air group (p ≤ 0.05). ERß expression in the epithelium and submucosa nucleus was lower in estrus exposed to CAPs compared with ambient air. CAPs increases AhR in the epithelium (p = 0.044) and submucosa (p = 0.001) nucleus of female when compared with male mice. Exposure to CAPs, also led to relatively increased acidic content in the mucus of males (p = 0.048), but decreased acidic content in that of females (p = 0.04). This study revealed sex-dependent responses to air pollution in the nasal epithelium that may partially explain the predisposition of females to airway respiratory diseases.

Efeitos da participação de esteroides-like provenientes da poluição atmosférica no epitélio das vias aéreas em camundongos machos e fêmeas / Effects of the participation of steroid-like compounds from air pollution in the airway epithelium of male and female mice

O epitélio nasal é a primeira porção do sistema respiratório a entrar em contato com o ambiente externo. Partículas da poluição do ar, principalmente os compostos orgânicos absorvidos, podem atuar como liberadores endócrinos. O receptor aril hidrocarboneto (AhR) é um importante competidor dos receptores de estrógeno-beta (ERbeta) que regulam a transcrição do gene para enzimas de metabolização xenobióticas (enzimas do citocromo P450). O objetivo deste estudo é identificar e quantificar ERbeta, AhR, CYP1A1, CYP1A2, CYP1B1 e o perfil de muco no epitélio nasal de camundongos machos e fêmeas em diferentes fases do ciclo estral. Camundongos BALB/c machos (n=32) e fêmeas (n=84) foram expostos ao ar ambiente e ao MP2,5 concentrado a 600 ug.m-³ em um concentrador de partículas ambientais (CPAs). As fêmeas foram divididas de acordo com as fases do ciclo estral: proestro, estro e diestro. O epitélio nasal foi avaliado por RT-PCR e imuno-histoquímica para análise de expressão de ERbeta (proteína), Erbeta-1 e Erbeta-2 (gene), AhR (proteína e gene) e Cyp1a1, Cyp1a2 and Cyp1b1 (gene). A quantificação de muco neutro - Periodic Acid Schiff's (PAS+) e ácido - Alcian Blue (AB+) foi avaliada por morfometria. As exposições foram realizadas durante 5 dias/semana, por 45 ± 55 dias. A expressão de Erbeta-2 RNAm apresentou diferenças em resposta à exposição ao CPAs (p=0,016), bem como uma diminuição em fêmeas, quando comparadas aos camundongos machos (p=0,036). A expressão de Cyp1b1 RNAm foi significantemente menor no grupo exposto ao CPAs, em relação ao grupo exposto ao ar ambiente nas fêmeas em diestro (p=0,036). A expressão de Erbeta foi aumentada no epitélio nasal de fêmeas em estro expostas ao CPAs (p=0,005) e a expressão de AhR foi menor em fêmeas em proestro expostas ao CPAs (p=0,048). A exposição ao CPAs levou ao aumento do conteúdo de muco ácido em camundongos machos (p=0,048), o qual diminuiu em fêmeas (p=0,040), quando comparados ao grupo ar ambiente. Este estudo mostrou...

The nasal epithelium is the first portion of the respiratory system to reach contact with the external environment. Air pollution particles, mainly the organic compounds absorbed into them, may act as endocrine releasers. The aryl hydrocarbon (AhR) receptor is an important competitor of estrogenic receptors-beta (ERbeta) that regulate transcription of gene coding for xenobiotic-metabolizing enzymes (cytochrome P450 enzymes). The aim of this study is to identify and quantify in the nasal epithelium of male and female mice in different estrous cycle phases related with ERbeta, AhR, CYP1A1, 1A2, 1B1 and the mucus profile. Male (n=32) and female (n=84) BALB/c mice were exposed to ambient air and PM2.5 concentrated at 600 ug.m-³ in an ambient particle concentrator with a particulate matter diameter of 2.5 um (PM2.5). Females were subdivided in three estrous cycles: proestrus, estrus and diestrus. Nasal epithelium was evaluated through RT-PCR and immunohistochemistry for the expression of ERbeta (protein), Erbeta-1 and Erbeta-2 (gene expression), AhR (protein and gene expression) and Cyp1a1, Cyp1a2 and Cyp1b1 (gene expression). Morphometry was applied for evaluation of mucus profile: acid - Alcian Blue (AB+) and neutral - Periodic Acid Schiff's (PAS+). Exposure happened for 5 days/week, for 45 ± 55 days. There were differences in Erbeta-2 mRNA in response to exposition to CPAs (p=0.016), and a significant decrease in female compared male mice (p=0.036). Cyp1b1 mRNA was significantly smaller in the CPAs-exposed group compared with the ambient air group in diestrus female mice (p=0.036). The ERbeta expression increased in the nasal epithelium of CPAs-exposed females in the estrus cycle (p=0.005), and the AhR expression decreased in the proestrus cycle of CPAs-exposed females (p=0.048). The exposure to the CPAs led to an increase in the acidic content of mucus in male mice (p=0.048), and decreased in female mice (p=0.040), compared to the ambient air group. This...