Grantee Research Project Results
Novel Methods to Assess Effects of Bisphenol A (BPA) & Phthalates on Child Development
EPA Grant Number: R834593Center: Water Innovation Network for Sustainable Small Systems
Center Director: Reckhow, David A.
Title: Novel Methods to Assess Effects of Bisphenol A (BPA) & Phthalates on Child Development
Investigators: Schantz, Susan L. , Korrick, Susan A. , Yi, Sandra James , Baillargeon, Renee L. , Aguiar, Andrea , Yao, Humphrey , Juraska, Janice , Flaws, Jodi , Gardnier, Joseph
Current Investigators: Schantz, Susan L. , Korrick, Susan A. , Juraska, Janice , Flaws, Jodi
Institution: University of Illinois Urbana-Champaign , Harvard University , Michigan State University
Current Institution: University of Illinois Urbana-Champaign , Harvard University
EPA Project Officer: Hahn, Intaek
Project Period: February 15, 2010 through February 14, 2014
Project Amount: $1,094,951
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
The primary objective of this Formative Children’s Center is to assemble a multidisciplinary team of experts to address critical gaps in our knowledge of the risks to children from Bisphenol A (BPA) and phthalate exposure. We will actively involve junior investigators and communicate the research findings to the health care community and public. Because both BPA and phthalates disrupt steroid hormone action, the studies will focus on endocrine-meditated outcomes including gonadal development and sexually dimorphic (differences between male and female) aspects of brain development and behavior.
Approach:
The impact of exposures during two developmental windows - the prenatal and the adolescent periods - will be assessed. At the heart of the research will be two human cohort studies - a pilot birth cohort in Urbana-Champaign, IL (Project 1;S.Schantz, PI) and a pilot adolescent cohort to be studied in the context of an ongoing study in New Bedford, MA (project 2; S. Korrick, PI). These studies will assess the relation of BPA or phthalate exposure to sexually dimorphic aspects of physical development and cognition in newborn infants and cognition in adolescent. This Center includes animal studies that will model the timing of exposure in the human cohorts. These studies will investigate mechanisms through which BPA disrupts male and female gonad development using transgenic (with genes from other organisms) and knockout (with specific genes deactivated) mouse models (Project 3; H. Yao, PI), and the impact of in utero or peripubertal BPA exposure on development of sexually dimorphic cortical brain regions and cognitive functions in a rat model (Project 4; J. Juraska, PI). While the two human studies will assess both phthalates and BPA, the animal studies will focus on BPA and later expand to include phthalates.
Expected Results:
Innovative use of analogous tests in animal and human studies, combined with mechanistic investigation (Projects 3,4), will optimize our ability to synthesize human and animal findings on BPA and phthalates. Data from these pilot studies is planned to provide the basis for further research studies. Central to the Center's long term goals are expansion of the pilot birth cohort into a larger prospective study with follow-up through puberty. This study would incorporate novel methods and approaches developed in the Formative Center. Another long term goal will be to expand the adolescent studies to include brain imaging. Studies in laboratory animal models would continue to play a key role, and would be used, both to explore mechanisms of action, and to identify key physical, biological and behavioral outcomes to assess in the children as they mature.
Journal Articles: 9 Displayed | Download in RIS Format
| Other center views: | All 35 publications | 9 publications in selected types | All 9 journal articles |
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Brannick KE, Craig ZR, Himes AD, Peretz JR, Wang W, Flaws JA, Raetzman LT. Prenatal exposure to low doses of bisphenol A increases pituitary proliferation and gonadotroph number in female mice offspring at birth. Biology of Reproduction 2012;87(4):82 (10 pp.). |
R834593 (2012) R834593C001 (Final) R834593C003 (2012) |
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Minihagalle S, You T, Suh L, Patel C, Gao L, Rattan S, Qiao H. Prenatal exposure to di-(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts mouse fetal oogenesis and affects folliculogenesis. BIOLOGY OF REPRODUCTION 2019;100(6):1561-1570. |
R834593 (Final) |
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Peretz J, Gupta RK, Singh J, Hernandez-Ochoa I, Flaws JA. Bisphenol A impairs follicle growth, inhibits steroidogenesis, and downregulates rate-limiting enzymes in the estradiol biosynthesis pathway. Toxicological Sciences 2011;119(1):209-217. |
R834593 (2012) R834593C001 (Final) R834593C003 (2012) |
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Peretz J, Craig ZR, Flaws JA. Bisphenol A inhibits follicle growth and induces atresia in cultured mouse antral follicles independently of the genomic estrogenic pathway. Biology of Reproduction 2012;87(3):63 (11 pp.). |
R834593 (2012) R834593C001 (Final) R834593C003 (2012) |
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Peretz J, Flaws JA. Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles. Toxicology and Applied Pharmacology 2013;271(2):249-256. |
R834593C001 (Final) |
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Peretz J, Vrooman L, Ricke WA, Hunt PA, Ehrlich S, Hauser R, Padmanabhan V, Taylor HS, Swan SH, VandeVoort CA, Flaws JA. Bisphenol A and reproductive health: update of experimental and human evidence, 2007-2013. Environmental Health Perspectives 2014;122(8):775-786. |
R834593C001 (Final) R835434 (2013) R835434 (2014) R835436 (2014) R835436 (2015) R835436 (2017) |
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Sadowski RN, Park P, Neese SL, Ferguson DC, Schantz SL, Juraska JM. Effects of perinatal bisphenol A exposure during early development on radial arm maze behavior in adult male and female rats. Neurotoxicology and Teratology 2014;42:17-24. |
R834593C001 (Final) |
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Sadowski RN, Wise LM, Park PY, Schantz SL, Juraska JM. Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females. Neuroscience 2014;279:122-131. |
R834593C001 (Final) |
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Shoaff JR, Calafat AM, Schantz, SL, Korrick SA. Endocrine Disrupting Chemical Exposure and Maladaptive Behavior during Adolescence. Environmental Research 2019;172:231-241. |
R834593 (Final) |
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Supplemental Keywords:
health effects, sensitive populations, genetic polymorphisms, epidemiologyProgress and Final Reports:
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834593C001 Prenatal Exposure to BPA/Phthalates: Infant Physical and Behavioral Development
R834593C002 Adolescent Exposure to BPA/Phthalates Cognitive and Behavioral Development
R834593C003 Mechanisms of In Utero BPA Exposure on Fetal Gonad Development
R834593C004 Effects of Bisphenol A on the Developing Cortex
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.