title: Maternal exposure to ambient PM2.5exaggerates fetal cardiovascular maldevelopment induced by homocysteine in rats.
abstract: Maternal exposure to airborne particulate matter with aerodynamic diameter <2.5 µm (PM2.5) during pregnancy and lactation periods is associated with filial congenital cardiovascular diseases. This study aimed to investigate the toxic effects of maternal exposure to ambient levels of PM2.5on filial cardiovascular maldevelopment induced by homocysteine. Using a 2 × 2 factorial design, rats were randomized into four groups and were exposed to ambient PM2.5or filtered air (FA) throughout the pregnancy and lactation periods coupled with the administration of either homocysteine (HCY) or normal saline (NS) daily from gestation days 8-10. Morphological changes in the heart, myocardial apoptosis, expressions of cardiac progenitor transcriptional factors, and levels of cytokines were investigated in the offspring. The apoptosis-like changes in the myocardium were seen in the FA plus HCY-treated group and more obviously in the PM2.5plus HCY-treated group, which was in accordance with an increased myocardial apoptosis rate in the two groups. PM2.5exposure resulted in significantly decreased Nkx2-5 protein level and GATA4 and Nkx2-5 mRNA expressions, and significantly increased TNF-α and IL-1β levels. There were significant interactions between PM2.5exposure and HCY-treatment that PM2.5exposure reduced Nkx2-5 protein levels and GATA4 and Nkx2-5 mRNA expressions in the HCY-treated groups. These results suggest that maternal exposure to PM2.5, even at the ambient levels in urban regions in China, exaggerates filial cardiovascular maldevelopment induced by HCY in a murine model, exacerbating structural abnormalities in the filial cardiac tissue, which is possibly associated with oxidative stress and reduced GATA4 and Nkx2-5 transcription factor expressions. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 877-889, 2017.
authors.affiliation: Department of Obstetrics and Gynecology, Fuzhou General Hospital, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Chen
authors.affiliation: Central Station of Environmental Monitoring of Fujian Province, Fuzhou, Fujian, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Fuzhou General Hospital, Fujian Medical University, Fuzhou, Fujian, China.|Dongfang Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.|China International Science & Technology Cooperation Base for Environmental Factors on Early Development, Fuzhou, Fujian, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Obstetrics and Gynecology, Fujian Maternity and Children Health Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Chaobin
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Fuzhou General Hospital, Fujian Medical University, Fuzhou, Fujian, China.|Dongfang Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Fuzhou Institute of Product Quality Inspection, Fuzhou, Fujian, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Fujian Maternity and Children Health Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Suqing
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Fujian Maternity and Children Health Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Hanqiang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Dongfang Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio, 43210-1240, USA.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D000072576:Homeobox Protein Nkx-2.5 / Q000235:genetics / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D018811:Maternal Exposure; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D000072576:Homeobox Protein Nkx-2.5; D053583:Interleukin-1beta; C484469:Nkx2-5 protein, mouse; D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha; D006710:Homocysteine
keywords: GATA4; Nkx2-5; airborne fine particulate matter; cardiovascular system; offspring