title: Maternal exposure to fine particulate air pollution induces epithelial-to-mesenchymal transition resulting in postnatal pulmonary dysfunction mediated by transforming growth factor-β/Smad3 signaling.
abstract: Fine particles from air pollution, also called particulate matter, less than 2.5 micrometers in diameter (PM2.5), are a threat to child health. Epidemiological investigations have related maternal exposure to PM2.5 to postnatal respiratory symptoms, such as frequent wheezing, chronic cough, and lung function decrements. However, only few experimental animal studies have been performed to study the effects of PM2.5.The aim of this study was to investigate the effects of maternal exposure to PM2.5 on postnatal pulmonary dysfunction in a rat model and to examine the mechanism of PM2.5-induced morphological pulmonary changes.Timed pregnant Sprague-Dawley rats were treated with PM2.5 (0.1, 0.5, 2.5, or 7.5mg/kg) once every three days from day 0 to 18 of pregnancy. After delivery, pups were sacrificed on postnatal day (PND)1 and 28. The effects of transforming growth factor-beta (TGF-β) on epithelial-mesenchymal transition (EMT) were determined by immunohistochemistry, Western blotting, and quantitative RT-PCR. The offspring underwent pulmonary function measurements on PND28, lung tissues were histopathologically examined, and markers of oxidative stress were measured. Maternally PM2.5-exposed offspring pups displayed significant decreases in lung volume parameters, compliance, and airflow during expiration on PND28. The PM2.5-exposed group showed interstitial proliferation in lung histology, significant oxidative stress in lungs, and up-regulation of TGF-β-induced EMT via increased vimentin and α-smooth muscle actin and decreased E-cadherin levels on PND1 and PND28.These results suggest that EMT up-regulation mediated by the TGF-β/Smad3 pathway plays a role in postnatal pulmonary dysfunction associated with maternal exposure to PM2.5.
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China; Department of Obstetrics and Gynecology, Dongguan People's Hospital, Dongguan,China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Organic Geochemistry, Guangdong Key Laboratory of Environment and Resources, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China.
authors.forename: Jingsi
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China. Electronic address: gzdrchen@gzhmu.edu.cn.
authors.forename: Dunjin
authors.initials: D
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018811:Maternal Exposure / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012129:Respiratory Function Tests; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D014746:Vimentin; C000610228:CDH1 protein, rat; C497787:Smad3 protein, rat; C498862:Acta2 protein, rat
keywords: EMT; Offspring; PM2.5; Pulmonary dysfunction