News | Science Selection Volume 121 | Issue 8 | August 2013
BPA and Altered Airway Cells: Association Seen in Rhesus Macaques after Third-Trimester Exposure
Lindsey Konkel is a Worcester, MA–based journalist who reports on science, health, and the environment. She writes frequently for Environmental Health News and The Daily Climate.
PDF Version (614 KB)
Fetal Exposure of Rhesus Macaques to Bisphenol A Alters Cellular Development of the Conducting Airway by Changing Epithelial Secretory Product Expression
Prenatal bisphenol A (BPA) exposure has been shown to alter the development of reproductive organs in animal models,1 although the impacts on development of other organ systems remain largely unknown. Researchers at the University of California, Davis, now report in EHP that BPA exposure late in gestation alters airway cell development in rhesus macaques.2
Previous studies have associated BPA exposure with an experimental model of asthma in mice.3 Epidemiological studies have found evidence of an association between prenatal BPA exposure and wheeze in young children,4 and between postnatal exposure and childhood asthma.5 “This study sheds light on the possible mechanisms by which BPA may affect lung health,” says Kathleen Donohue, an assistant professor of medicine at Columbia University. Donohue was not involved in the current study.
BPA exposure is widespread. One report from the National Health and Nutrition Examination Survey found that more than 90% of urine samples collected from U.S. males and females over age 6 years contained detectable levels of the chemical.6
For the current study, pregnant rhesus macaques received BPA via subcutaneous implant for 50 days during gestational days 50–100 or 100–150 (roughly comparable to the second and third trimesters, respectively, in humans). Control macaques received a corn oil implant or ate corn oil–treated fruit. Treatment groups included at least 6 animals, with histopathologic analyses conducted on smaller subgroups.
“Our goal was to model constant serum levels of BPA that have been measured in humans,” says first author Laura Van Winkle, a toxicologist at the university. “Lung development patterns and cellular abundance in the airways of these animals match humans much more closely than rodent models.”
At the end of each group’s exposure period the researchers collected fetal airway tissue samples. They used only female fetuses, as the study originated from a project designed to examine the effects of BPA on female reproductive development.
They found that BPA exposure in late pregnancy was associated with increased expression of secretory proteins in fetal tissue. The cells that produce these proteins mature late in gestation; the proteins themselves—Clara cell secretory protein (CCSP) and the mucins MUC5AC and MUC5B—are key components of airway mucous secretions.2
Expression of the Muc5B gene was approximately six times higher at 150 days’ gestation in fetuses whose mothers were exposed to BPA late in pregnancy compared with those whose mothers received no BPA exposure. Expression of the Muc5AC gene also was increased. Histological staining of the lung tissue indicated there were more mucous cells in the airway epithelium of exposed fetuses and suggested an increase in the amount of mucous production (however, the researchers did not have a large enough sample size to run statistical analyses).2
There were no significant changes in protein expression after exposure during mid-pregnancy, suggesting that late pregnancy may be a critical period in which BPA exposure may alter airway cell development. This critical window may also apply to human exposures to BPA in the third trimester of pregnancy due to similarities in the timing of cellular development and airway structure between rhesus macaques and humans.2
“Taken together with earlier studies in humans, this study in monkeys is important because it is another link in the chain of evidence [potentially] connecting BPA exposure to lung disease,” says Donohue.
An increase in mucous cell abundance is one of the hallmarks of asthma, the authors report. However, they say, the clinical relevance of this particular study remains to be seen. The researchers examined only fetal airway tissue samples, and it is unknown whether an increase in mucous cell abundance would have resulted in airway disease after birth.
The potential effects of environmental estrogens such as BPA on lung development also are not well known, says Van Winkle. Although estrogen is known to increase the expression of MUC5B in cultured airway epithelium cells from humans,7 and lung tissue does have estrogen receptors,8 it’s not clear how this affects the development of secretory proteins.
Recent experimental studies have suggested that BPA may also disrupt fetal development through epigenetic and nonestrogenic pathways.9,10 Van Winkle suspects a combination of hormonal and nonhormonal effects may be at play. “A third possibility is that BPA affects something else entirely in the body that in turn alters lung development,” she says.
1. vom Saal FS, et al. Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. Reprod Toxicol 24(2):131–138 (2007); http://dx.doi.org/.10.1016/j.reprotox.2007.07.005.
2. Van Winkle LS, et al. Fetal exposure of rhesus macaques to bisphenol A alters cellular development of the conducting airway by changing epithelial secretory product expression. Environ Health Perspect 121(8):912–918 (2013); http://dx.doi.org/.10.1289/ehp.1206064.
3. Midoro-Horiuti T, et al. Maternal bisphenol A exposure promotes the development of experimental asthma in mouse pups. Environ Health Perspect 118(2):273–277 (2010); http://dx.doi.org/.10.1289/ehp.0901259.
4. Spanier AJ, et al. Prenatal exposure to bisphenol A and child wheeze from birth to 3 years of age. Environ Health Perspect 120(6):916–920 (2012); http://dx.doi.org/.10.1289/ehp.1104175.
5. Donohue KM, et al. Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children. J Allergy Clin Immunol 131(3):736–742 (2013); http://dx.doi.org/.10.1016/j.jaci.2012.12.1573.
6. Calafat AM, et al. Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003–2004. Environ Health Perspect 116(1):39–44 (2008); http://dx.doi.org/10.1289/ehp.10753.
7. Choi HJ, et al. Signal pathway of 17β-estradiol-induced MUC5B expression in human airway epithelial cells. Am J Respir Cell Mol Biol 40(2):168–178 (2009); http://dx.doi.org/10.1165/rcmb.2007-0377OC.
8. Mollerup S, et al. Expression of estrogen receptors α and β in human lung tissue and cell lines. Lung Cancer 37(2):153–159 (2002); http://dx.doi.org/10.1016/S0169-5002(02)00039-9.
9. Susiarjo M, et al. Bisphenol A exposure disrupts genomic imprinting in the mouse. PLoS Genet 9(4):e1003401 (2013); http://dx.doi.org/10.1371/journal.pgen.1003401.
10. Vandenberg LN, et al. Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev 30(1):75–95 (2009); http://dx.doi.org/10.1210/er.2008-0021.
New Impact Factor
We are pleased to announce our new impact factor of 7.03 and—for the first time—our inclusion in the category of Toxicology. Thank you to our authors and readers, who continue to make EHP a leading journal in Environmental Sciences, in Public, Environmental, and Occupational Health, and now in Toxicology.
EHP News Feature Wins Award
Our March 2013 cover story, “A Tale of Two Forests: Addressing Postnuclear Radiation at Chernobyl and Fukushima,” has won first place in the Outstanding Feature Story category of the Society of Environmental Journalists Awards for Reporting on the Environment. The judges called the story “an exceedingly vital and original piece of environmental feature writing.” Congratulations to authors Winifred A. Bird and Jane Braxton Little on their exciting achievement!
CEHN August 2014 Article of the Month
“Gestational Exposure to Endocrine-Disrupting Chemicals and Reciprocal Social, Repetitive and Stereotypic Behaviors in 4- and 5-Year-Old Children: The HOME Study” (Environ Health Perspect; DOI:10.1289/ehp.1307261) has been selected by the Children’s Environmental Health Network (CEHN) as its August 2014 Article of the Month. These CEHN summaries discuss the potential policy implications of current children’s environmental health research.
Register Today for PPTOX IVEnvironmental Stressors in Disease and Implications for Human Health
October 26–29, 2014
Boston Marriott Long Wharf Hotel
Join the Endocrine Society for the fourth international summit of Prenatal Programming and Toxicity (PPTOX), a premiere conference series dedicated to cutting-edge discussion of environmental hazards during early life and long-term consequences.Key deadlines:
* Abstract submission: Tuesday, September 2
* Housing deadline: Monday, October 6
For more information, visit the Endocrine Society website.
Sign Up to Receive E-mail Alerts
Recent Advance Publications
- Effect of Exposure to Atmospheric Ultrafine Particles on Production of Free Fatty Acids and Lipid Metabolites in the Mouse Small Intestine
- Risks and Benefits of Green Spaces for Children: A Cross-Sectional Study of Associations with Sedentary Behavior, Obesity, Asthma, and Allergy
- Genistein Disrupts Glucocorticoid Receptor Signaling in Human Uterine Endometrial Ishikawa Cells
- Modification of the Association between PM10 and Lung Function Decline by Cadherin 13 Polymorphisms in the SAPALDIA Cohort: A Genome-Wide Interaction Analysis
- Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress
- Incense Use and Cardiovascular Mortality among Chinese in Singapore: The Singapore Chinese Health Study
- Perfluorochemicals and Human Semen Quality: The LIFE Study
- AdvPubl: Atmospheric ultrafine particles and intestinal lipid metabolism http://t.co/flqRKKLMep
- Trending EHP news this month: Nanosilver: weighing the risks and benefits http://t.co/6oSYgL8MNO
- Trending EHP research this month: The societal costs and benefits of commuter bicycling http://t.co/yGlks7cL5l
- EHPNoonNews: Big Food to divulge chemical info http://t.co/jaCI6PWQRx @washingtonpost EHP lookback http://t.co/1eRkamlSkF
- EHPNoonNews: EPA identifies health concern from chemical used in paint strippers http://t.co/yMIisVom4Y @epa