Prenatal Bisphenol A Exposure and Early Childhood Behavior
Joe M. Braun1, Kimberly Yolton2, Kim N. Dietrich3, Richard Hornung2, Xiaoyun Ye4,
Antonia M. Calafat4, Bruce P. Lanphear2,5

1-Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC,
27514
2-Department of Pediatrics, Division of General and Community Pediatrics, Cincinnati
Children's Hospital Medical Center, Cincinnati, OH 45229
3-Department of Environmental Health, Division of Epidemiology and Biostatistics, University
of Cincinnati College of Medicine, Cincinnati, OH 45267
4- Division of Laboratory Sciences, National Center for Environmental Health, Centers for
Disease Control and Prevention, Atlanta, GA 30341
5-Child & Family Research Institute, BC Children’s Hospital and the Faculty of Health Sciences,
Simon Fraser University, Vancouver, British Columbia

Abstract
Background: Prenatal exposure Bisphenol A (BPA) increases offspring aggression and
diminishes differences in sexually dimorphic behaviors in rodents.
Objective: We examined the association between prenatal BPA exposure and behavior in 2-year
old children.
Methods: We used data from 249 mothers and their children in Cincinnati OH. Maternal urine
was collected around 16 and 26 weeks gestation and at birth. BPA concentrations were
quantified using high performance liquid chromatography-isotope dilution-tandem mass
spectrometry. Child behavior was assessed at 2-years of age using the Behavioral Assessment
System for Children-2 (BASC-2). The association between prenatal BPA concentrations and
BASC-2 scores was analyzed using linear regression.
Results: Median BPA concentrations were 1.8 (16 week), 1.7 (26 week), and 1.3 (birth) ng/ml.
Mean externalizing and internalizing scores were 47.6 (standard deviation [SD]:7.8) and 44.8
(SD:7.0), respectively. After adjustment for confounders, log10-transformed mean prenatal BPA
concentrations were associated with externalizing scores, but only among females (:6.0; 95%
confidence interval [CI]:0.1, 12.0). Compared to 26 week and birth concentrations, BPA
concentrations collected around 16 weeks were more strongly associated with externalizing
scores among all children (:2.9; 95% CI: 0.2, 5.7); and this association was stronger in females
than males. Among all children, measurements collected < 16 weeks showed a stronger
association (:5.1; 95% CI:1.5, 8.6) with externalizing scores than measurements taken from 17-
21 weeks (:0.6, 95% CI:-2.9, 4.1).
Conclusions: These results suggest that prenatal BPA exposure may be associated with
externalizing behaviors in two-year old children, especially among female children.

Environ Health Perspect doi:10.1289/ehp.0900979 available via http://dx.doi.org/ [Online 06 October 2009]

Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

Nature advance online publication 8 October 2008 | doi:10.1038/nature07404

Context Bisphenol A (BPA) is widely used in epoxy resins lining food and beverage containers. Evidence of effects in animals has generated concern over low-level chronic exposures in humans.

Objective To examine associations between urinary BPA concentrations and adult health status.

Design, Setting, and Participants Cross-sectional analysis of BPA concentrations and health status in the general adult population of the United States, using data from the National Health and Nutrition Examination Survey 2003-2004. Participants were 1455 adults aged 18 through 74 years with measured urinary BPA and urine creatinine concentrations. Regression models were adjusted for age, sex, race/ethnicity, education, income, smoking, body mass index, waist circumference, and urinary creatinine concentration. The sample provided 80% power to detect unadjusted odds ratios (ORs) of 1.4 for diagnoses of 5% prevalence per 1-SD change in BPA concentration, or standardized regression coefficients of 0.075 for liver enzyme concentrations, at a significance level of P < .05.

Main Outcome Measures Chronic disease diagnoses plus blood markers of liver function, glucose homeostasis, inflammation, and lipid changes.

Results Higher urinary BPA concentrations were associated with cardiovascular diagnoses in age-, sex-, and fully adjusted models (OR per 1-SD increase in BPA concentration, 1.39; 95% confidence interval [CI], 1.18-1.63; P = .001 with full adjustment). Higher BPA concentrations were also associated with diabetes (OR per 1-SD increase in BPA concentration, 1.39; 95% confidence interval [CI], 1.21-1.60; P < .001) but not with other studied common diseases. In addition, higher BPA concentrations were associated with clinically abnormal concentrations of the liver enzymes {gamma}-glutamyltransferase (OR per 1-SD increase in BPA concentration, 1.29; 95% CI, 1.14-1.46; P < .001) and alkaline phosphatase (OR per 1-SD increase in BPA concentration, 1.48; 95% CI, 1.18-1.85; P = .002).

Conclusion Higher BPA exposure, reflected in higher urinary concentrations of BPA, may be associated with avoidable morbidity in the community-dwelling adult population.

JAMA. 2008;300(11):1303-1310. Published online September 16, 2008 (doi:10.1001/jama.300.11.1303)

In this issue of JAMA, Lang and colleagues1 report the results of the first major epidemiologic study to examine the health effects associated with the ubiquitous estrogenic chemical bisphenol A (BPA). This compound is the base chemical (monomer) used to make polycarbonate plastic food and beverage containers, the resin lining of cans, and dental sealants; it also is found in "carbonless" paper used for receipts as well as a wide range of other common household products. Based on their analysis of data from the National Health and Nutrition Examination Survey 2003-2004, Lang et al report a significant relationship between urine concentrations of BPA and cardiovascular disease, type 2 diabetes, and liver-enzyme abnormalities in a representative sample of the adult US population. This report, suggesting links between BPA and some of the most significant and economically burdensome human diseases, is based . . .

JAMA. 2008;300(11):1353-1355. Published online September 16, 2008 (doi:10.1001/jama.300.11.1353)

Background: The incidence of obesity has risen dramatically over the last few decades. This
epidemic may be affected by exposure to xenobiotic chemicals. Bisphenol A (BPA), an
endocrine disruptor, is detectable at nM levels in human serum worldwide. Adiponectin is an
adipocyte-specific hormone which increases insulin sensitivity and reduces tissue inflammation.
Thus, any factor which suppresses adiponectin release could lead to insulin resistance and
increased susceptibility to obesity-associated diseases.

Objectives: To compare: a) the effects of low doses of BPA and estradiol (E2) on adiponectin
secretion from human breast, subcutaneous (sc) and visceral (vis) adipose explants and mature
adipocytes, and b) expression of putative estrogen and estrogen-related receptors in these tissues.

Methods: Adiponectin levels in conditioned media (CM) from adipose explants or adipocytes
were determined by enzyme-linked immunosorbant assay (ELISA). Expression of estrogen
receptors (ER) α and β, G-protein-coupled receptor 30 (GPR30), and estrogen-related receptors
(ERR) α, β and γ was determined by quantitative real-time PCR.

Results: BPA at 0.1 and 1 nM doses suppressed adiponectin release from all adipose depots
examined. In spite of a substantial variability among patients, BPA was as effective, and often
more effective, than equimolar concentrations of E2. Adipose tissue expresses similar mRNA
levels of ERα, ERβ and ERRγ, and 20-30 fold lower levels of GPR30, ERRα and ERRβ.

Conclusions: BPA at environmentally-relevant doses inhibits the release of a key adipokine that
protects humans from the metabolic syndrome. The mechanism by which BPA suppresses
adiponectin and the receptors involved remain to be determined.

Environ Health Perspect doi:10.1289/ehp.11537 available via http://dx.doi.org/ [Online 14 August 2008]

Concern about potential health impacts of low-level exposures to organophosphorus (OP) pesticides, bisphenol A (BPA), and phthalates among the general population is increasing. We measured levels of six dialkyl phosphate (DAP) metabolites of OP pesticides, a chlorpyrifos-specific metabolite (3,5,6-trichloro-2-pyridinol, TCPy), BPA, and 14 phthalate metabolites in urine samples of 100 pregnant women from the Generation R study, the Netherlands. The unadjusted and creatinine-adjusted concentrations were reported, and compared to National Health and Nutrition Examination Survey and other studies. In general, these metabolites were detectable in the urine of the women from the Generation R study and compared with other groups, they had relatively high-level exposures to OP pesticides and several phthalates but similar exposure to BPA. The median concentrations of total dimethyl (DM) metabolites was 264.0nmol/g creatinine (Cr) and of total DAP was 316.0nmol/g Cr. The median concentration of mono-ethyl phthalate (MEP) was 222.0mug/g Cr; the median concentrations of mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) were above 50mug/g Cr. The median concentrations of the three secondary metabolites of di-2-ethylhexyl phthalate (DEHP) were greater than 20mug/g Cr. The data indicate that the Generation R study population provides a wide distribution of selected environmental exposures. Reasons for the relatively high levels and possible health effects need investigation.

Environ Res. 2008 Sep 4. [Epub ahead of print]

Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81–base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain.

Science 5 September 2008: Vol. 321. no. 5894, pp. 1346 - 1350
DOI: 10.1126/science.1159974