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)

The Frizzled (Fz) receptor is required cell autonomously in Wnt/β-catenin and planar cell polarity (PCP) signaling. In addition to these requirements, Fz acts nonautonomously during PCP establishment: wild-type cells surrounding fz− patches reorient toward the fz− cells. The molecular mechanism(s) of nonautonomous Fz signaling are unknown. Our in vivo studies identify the extracellular domain (ECD) of Fz, in particular its CRD (cysteine rich domain), as critical for nonautonomous Fz-PCP activity. Importantly, we demonstrate biochemical and physical interactions between the FzECD and the transmembrane protein Van Gogh/Strabismus (Vang/Stbm). We show that this function precedes cell-autonomous interactions and visible asymmetric PCP factor localization. Our data suggest that Vang/Stbm can act as a FzECD receptor, allowing cells to sense Fz activity/levels of their neighbors. Thus, direct Fz-Vang/Stbm interactions represent an intriguing mechanism that may account for the global orientation of cells within the plane of their epithelial field.

Developmental Cell, Vol 15, 462-469, 16 September 2008

Serum response factor (SRF) is a transcription factor that controls the expression of cytoskeletal proteins and immediate early genes in different cell types. Here, we found that SRF expression is restricted to endothelial cells (ECs) of small vessels such as capillaries in the mouse embryo. EC-specific Srf deletion led to aneurysms and hemorrhages from 11.5 days of mouse development (E11.5) and lethality at E14.5. Mutant embryos presented a reduced capillary density and defects in EC migration, with fewer numbers of filopodia in tip cells and ECs showing defects in actin polymerization and intercellular junctions. We show that SRF is essential for the expression of VE-cadherin and β-actin in ECs both in vivo and in vitro. Moreover, knockdown of SRF in ECs impaired VEGF- and FGF-induced in vitro angiogenesis. Taken together, our results demonstrate that SRF plays an important role in sprouting angiogenesis and small vessel integrity in the mouse embryo.

Developmental Cell, Vol 15, 448-461, 16 September 2008

The function of pancreatic β-cells is the synthesis and release of insulin, the main hormone involved in blood glucose homeostasis. Estrogen receptors, ERα and ERβ, are important molecules involved in glucose metabolism, yet their role in pancreatic β-cell physiology is still greatly unknown. In this report we show that both ERα and ERβ are present in pancreatic β-cells. Long term exposure to physiological concentrations of 17β-estradiol (E2) increased β-cell insulin content, insulin gene expression and insulin release, yet pancreatic β-cell mass was unaltered. The up-regulation of pancreatic β-cell insulin content was imitated by environmentally relevant doses of the widespread endocrine disruptor Bisphenol-A (BPA). The use of ERα and ERβ agonists as well as ERαKO and ERβKO mice suggests that the estrogen receptor involved is ERα. The up-regulation of pancreatic insulin content by ERα activation involves ERK1/2. These data may be important to explain the actions of E2 and environmental estrogens in endocrine pancreatic function and blood glucose homeostasis.

PLoS ONE 3(4): e2069. doi:10.1371/journal.pone.0002069

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]