Prenatal exposure to bisphenol A disrupts mouse fetal lung development.
Developmental exposure to bisphenol A (BPA) is associated with lung dysfunction and diseases. However, it is unknown if this association has a fetal origin. The present study addressed this important question by examining the effects of BPA on fetal lung development. BPA was administered to pregnant mice via diet from embryonic day (E) 7.5 to E18.5. Fetal lungs were analyzed at E18.5 for changes in structure and expression of key molecular markers of lung maturation. Our main findings were as follows: BPA severely retards fetal lung maturation, as evidenced by diminished alveolar airspace (15% of control) and thickened septa, hallmarks of lung immaturity; this immaturity is characterized by aberrant alveolar epithelial type I cell differentiation because expression of the type I cell marker, aquaporin 5, but not type II cell markers, is dramatically reduced (16% of control); and the effects of BPA are likely mediated through the glucocorticoid signaling pathway because the expression of epithelial sodium channel γ and glutathione peroxidase, 2 well-known glucocorticoid target genes, is down-regulated in BPA-exposed fetal lungs, and, importantly, maternal dexamethasone administration rescues the lung immaturity phenotype. Taken together, these findings demonstrate that BPA disrupts fetal lung maturation, thus suggesting a fetal origin for BPA-induced lung diseases.
Department of Obstetrics and Gynaecology and Department of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, Western University, London, Ontario, Canada.
Ayten
A
Hijazi
Department of Obstetrics and Gynaecology and Department of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, Western University, London, Ontario, Canada.
Haiyan
H
Guan
Department of Obstetrics and Gynaecology and Department of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, Western University, London, Ontario, Canada.
Maria
M
Cernea
Department of Obstetrics and Gynaecology and Department of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, Western University, London, Ontario, Canada kyang@uwo.ca.
Kaiping
K
Yang
D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000196:embryology; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D003345:Corticosterone; D003907:Dexamethasone; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
endocrine-disrupting chemical; environmental exposure; glucocorticoid signaling; lung maturation