Between Bisphenol A Research Articles

Lung inflammation induced by exposure to Bisphenol-A is associated with mTOR-mediated autophagy in adolescent mice

Epidemiologic studies show that there is a link between Bisphenol A (BPA) exposure and lung inflammation. Despite this, the molecular mechanisms are not entirely known. This study sought to determine whether exposure to BPA affected the development of ovalbumin (OVA) induced lung inflammation in adolescent female mice and whether the mechanism was related to mTOR-mediated autophagy pathway. Female 4-week-old C57BL/6 mice after one week of domestication were randomly divided into five groups (8/group): control group, OVA group, 0.1 μg mL−1 BPA + OVA group, 0.2 μg mL−1 BPA + OVA group and 0.4 μg mL−1 BPA + OVA group. BPA exacerbated airway hyperresponsiveness (AHR), induced the pathological changes in the lung, which also enhanced inflammatory cells and cytokine levels. In addition, BPA exposure affected expression of autophagy associated proteins and genes. This research results indicated that BPA aggravated OVA-induced lung inflammation and induced abnormal immune function in mice, and its mechanism was related to the activation of autophagy pathway by down-regulation expression of mTOR. These findings suggest that therapeutic strategies to target autophagy may offer a new approach for severe asthma therapy.

Bisphenol a Exposure, DNA Methylation, and Asthma in Children.

Epidemiological studies have reported the relationship between bisphenol A (BPA) exposure and increased prevalence of asthma, but the mechanisms remain unclear. Here, we investigated whether BPA exposure and DNA methylation related to asthma in children. We collected urinary and blood samples from 228 children (Childhood Environment and Allergic Diseases Study cohort) aged 3 years. Thirty-three candidate genes potentially interacting with BPA exposure were selected from a toxicogenomics database. DNA methylation was measured in 22 blood samples with top-high and bottom-low exposures of BPA. Candidate genes with differential methylation levels were validated by qPCR and promoter associated CpG islands have been investigated. Correlations between the methylation percentage and BPA exposure and asthma were analyzed. According to our findings, MAPK1 showed differential methylation and was further investigated in 228 children. Adjusting for confounders, urinary BPA glucuronide (BPAG) level inversely correlated with MAPK1 promoter methylation (β = −0.539, p = 0.010). For the logistic regression analysis, MAPK1 methylation status was dichotomized into higher methylated and lower methylated groups with cut off continuous variable of median of promoter methylation percentage (50%) while performing the analysis. MAPK1 methylation was lower in children with asthma than in children without asthma (mean ± SD; 69.82 ± 5.88% vs. 79.82 ± 5.56%) (p = 0.001). Mediation analysis suggested that MAPK1 methylation acts as a mediation variable between BPA exposure and asthma. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation.

Developing an epoxy resin with high toughness for grouting material via co-polymerization method

AbstractIn order to improve the toughness of epoxy resin for grouting material, the flexible hexamethylene diisocyanate (HDI) was utilized to manufacture a new kind of epoxy resin with high toughness via co-polymerization method. In the procedure of preparing bisphenol A epoxy resin, before the reaction between bisphenol A (BPA) and epichlorohydrin (ECH), HDI was introduced to react with BPA for embedding flexible segments into the chain of epoxy resin, then modified epoxy resin (HDI/EP) was manufactured. The mechanical properties, especially the toughness of the HDI/EP, are significantly increased – the fracture elongation is up to 124%. In addition, the compressed specimens can fully recover to their original shape in a few minutes. Thermal performance and corrosion resistance of the HDI/EP specimen were also investigated, which showed that the specimen can be used under 258°C, and can remain stable in H2SO4, NaOH and NaCl solutions with 10 wt% for 100 h, respectively. The present work provides a convenient avenue pathway to prepare an epoxy resin with high toughness, which may be used in many technologies.

A Study on Impact of BPA in the Adipose Tissue Dysfunction (Adiposopathy) in Asian Indian Type 2 Diabetes Mellitus Subjects.

A surge to increase the production via usage of chemicals at both industrial and agricultural arena has forced humans to be routinely and imprudently exposed to a wide variety of endocrine disrupting chemicals. The overall aim of the study was to evaluate possible relation that might exist between bisphenol-A (BPA) and the adipose tissue hormones, and further impact on adiposopathy. In the present study, the role of BPA, an "endocrine disruptor" with respect to adiposopathy was evaluated in type 2 diabetes mellitus patients. For the study, 150 healthy control subjects and 150 newly diagnosed diabetes patients were recruited. Fasting venous blood samples was analyzed for several biochemical parameters such as serum glucose, lipid profile, insulin, adiponectin, leptin, TNF-α, IL-6, IL-1, free fatty acid. Concentrations of BPA were also measured both in control and diabetic subjects. Serum BPA concentration was found to be significantly higher in diabetic subjects in comparison to the control subjects. Levels of BPA were found to be positively correlated with BMI and WC in diabetic subjects. Also, it was found to be positively correlated with leptin and negatively correlated with adiponectin in diabetic subjects. Therefore, the current study suggested more deleterious effect of BPA on diabetes and its pathophysiology.

Bisphenol A, Chlorinated Derivatives of Bisphenol A and Occurrence of Myocardial Infarction in Patients with Type 2 Diabetes: Nested Case-Control Studies in Two European Cohorts.

A positive association between Bisphenol A (BPA) exposure and coronary heart disease has been shown, but not in patients with type 2 diabetes (T2D). During the treatment of drinking water, chlorination leads to the formation of chlorinated derivatives of Bisphenol A (ClxBPA), that have higher estrogenic activity than BPA. No evidence exists for a relationship between exposure to ClxBPA and myocardial infarction in patients with T2D. The objective of this study was to evaluate the relationship between exposure to BPA, ClxBPA and the occurrence of myocardial infarction (MI) in patients with T2D. Two nested case-control studies in two independent European cohorts were performed. Each case with incident MI during follow-up was matched to one control on age, sex, and personal cardiovascular history in the same cohort. Association between baseline urine concentrations of BPA and of ClxBPA and incident MI was determined. Exposure to BPA was 31% in the ESTHER cohort and 18% in the SURDIAGENE cohort. In a meta-analysis of the two studies, occurrence of MI was significantly associated with urine BPA detection: adjusted OR = 1.97 (1.05-3.70), p = 0.04. Exposure to ClxBPA significantly differed in the SURDIAGENE and ESTHER studies: 24% and 8%, respectively (p = 0.0003). It was very strongly associated with MI in the SURDIAGENE cohort with an adjusted odds ratio (OR) of 14.15 (2.77-72.40) but this association was not replicated in the ESTHER study: adjusted OR: 0.17 (0.02-1.23). Whether these results may be explained by different water chlorination processes in France and Germany, resulting in different ClxBPA exposure levels, requires further investigation.

Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States.

The relationship between bisphenol A (BPA) and non-alcoholic fatty liver disease (NAFLD) is undefined. We studied the impact of BPA on NAFLD. We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014 among adults in the United States (US). NAFLD was diagnosed using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver diseases. The first sample using HSI consisted of 7605 adults. The second sample using USFLI consisted of 3631 participants with availability of fasting data. Of the first 7605 participants (mean age 47years, 48.4% male), the prevalence of NAFLD and abnormally elevated alanine aminotransferase (ALT) levels was correlated with urinary BPA levels (P<0.05). Compared to the reference group with lowest quartile of urinary BPA levels, those with the third and fourth quartiles were 81% and 53% more likely to develop NAFLD defined by HSI. In a multivariate model, the ORs for NAFLD in the third and fourth quartiles were 1.69 (95% CI 1.39-2.04) and 1.44 (95% CI 1.19-1.76) respectively (P for trend <0.001). In the second sample using USFLI, high BPA levels (fourth quartile) remained an independent predictor of NAFLD (OR 1.44, 95% CI 1.05-1.98, P for trend=0.012). High levels of urinary BPA were associated with NAFLD in a nationally representative sample of adults in the US. The pathophysiology remains unclear and warrants further investigation.

The role of hypothalamus polycomb gene methylation in bisphenol A exposure during pregnancy and premature puberty in female offspring

Objective: To explore the role of hypothalamus Polycomb Group (PcG) gene (Eed, Ezh) methylation in the relationship between bisphenol A (BPA) exposure during pregnancy and premature puberty in female offspring. Methods: A total of 40 pregnant CD-1 mice were randomly and averagely assigned into four groups: control group (corn oil) and low, middle and high BPA-exposed groups (the poisonous doses were 8 mg/kg, 40 mg/kg, and 200 mg/kg, respectively) by random number table method. Each group was administered by gavage from gestational day (GD) 1 to 18. The vaginal opening of female offspring was observed from postnatal day (PND) 21 to 33. All female offsprings were sacrificed, and hypothalamus was remained on the PND 34. The methylation levels of Eed and Ezh in the hypothalamus were measured. The early puberty of CD-1 mice was evaluated by the rate of vaginal opening in advance, initial time of vaginal opening, the first estrus occurrence and vaginal opening days in advance. The path model was used to explore the role of Eed and Ezh gene methylation in the early puberty of female offspring with maternal BPA exposed including the number of days of vaginal opening in advance as a dependent variable and BPA exposure as an independent variable. Results: The rate of vaginal opening on the 28 day in each maternal BPA-exposure group [low, middle and high BPA-exposed groups were 40.00% (29/72), 47.62% (25/53) and 37.84% (20/53), respectively] was higher than that rate in the control group [14.06%(9/64)]. Similarly, the P(50)(P(25), P(75)) values of initial time of vaginal opening in low, middle and high BPA-exposed group were 28 (26, 30), 28 (26, 29), 28 (26, 30) days, respectively and the P(50)(P(25), P(75)) values of the first estrus occurrence in low, middle and high BPA-exposed group were 31 (27, 32), 30 (27, 31), 31 (28, 33) days, respectively, which were earlier than those in the control group [initial time of vaginal opening was 30(28, 31) days, and the first estrus occurrence was 32(30, 33) days] (all P values<0.05). Compared with the control group (the methylation levels of Eed1, Eed2, Ezh2 were 1.47%, 1.26%, 2.56%, respectively), the methylation levels of Eed1 (1.61%-1.82%), Eed2 (1.36%-1.43%) and Ezh2 (2.87%-3.05%) in female offspring were significantly higher in BPA-exposed groups (all P values<0.05). The results of path model analysis showed that BPA had no direct influence on puberty in advance, but had an indirect effect on puberty in advance (indirect effect path coefficient was 0.045 and 0.142, respectively) by mediating methylation of Eed2, and Ezh2. Conclusion: Early puberty in female offspring induced by maternal exposure to BPA during pregnancy through the increased methylation levels of hypothalamus PcG gene (Eed, Ezh) in female offspring.

Bisphenol A binding promiscuity: A virtual journey through the universe of proteins.

Significant efforts are currently being made to move toxicity testing from animal experimentation to human relevant, mechanism-based approaches. In this context, the identification of molecular target(s) responsible for mechanisms of action is an essential step. Inspired by the recent concept of polypharmacology (the ability of drugs to interact with multiple targets) we argue that whole proteome virtual screening might become a breakthrough tool in toxicology reflecting the real complexity of chemical-biological interactions. Therefore, we investigated the value of performing ligand-protein binding prediction screening across the full proteome to identify new mechanisms of action for food chemicals. We applied the new approach to make a broader comparison between bisphenol A (BPA) (food-packaging chemical) and the endogenous estrogen, 17β-estradiol (EST). Applying a novel high-throughput ligand-protein binding prediction tool (BioGPS) by the Amazon Web Services (AWS) cloud (to speed-up the calculation), we investigated the value of performing in silico screening across the full proteome (all human and rodent x-ray protein structures available in the Protein Data Bank). The strong correlation between in silico predictions and available in vitro data demonstrates the high predictive power of the method used. The most striking results obtained was that BPA was predicted to bind to many more proteins than the ones already known, most of which were common to EST. Our findings provide a new and unprecedented insight on the complexity of chemical-protein interactions, highlighting the binding promiscuity of BPA and its broader similarity compared to the female sex hormone, EST.

Associations between Maternal Exposure to Bisphenol A or Triclosan and Gestational Hypertension and Preeclampsia: The MIREC Study.

Little is known about the association between bisphenol A (BPA) or triclosan (TCS) exposure and hypertension in pregnancy. To investigate potential associations between maternal urinary concentrations of BPA or TCS and gestational hypertension (GH) and preeclampsia. Among 1,909 pregnant women participating in the maternal-infant research on environmental chemicals (MIREC) study, urinary concentrations of BPA and TCS were measured in the first trimester by liquid chromatography-tandem mass spectrometry using isotope dilution. Blood pressure was measured during each trimester. Multinomial regression was performed to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) for the associations between these phenols and GH and preeclampsia. BPA and TCS were not associated with GH or preeclampsia. However, in multiparous women, BPA (0.50-1.30 µg/L) was associated with decreased risk of GH (aOR =0.45; 95%CI: 0.21-0.98) while among nulliparous women, TCS was associated with an increased risk of GH (3.60-32.60 µg/L; aOR = 2.58; 95% CI: 1.09-6.13 and > 32.60 µg/L: aOR = 2.74; 95% CI: 1.15-6.51). BPA and TCS urinary concentrations were not associated with GH or preeclampsia; however, our results suggest an association between TCS and GH in nulliparous women. Additional studies are required to confirm our results.

Associations between Maternal Exposure to Bisphenol A or Triclosan and Gestational Hypertension and Preeclampsia: The MIIREC Study

Background: Little is known about the association between bisphenol A (BPA) or triclosan (TCS) exposure and hypertension in pregnancy.Objective: To investigate potential associations between maternal urinary concentrations of BPA or TCS and gestational hypertension and preeclampsia.Methods: Among 1909 pregnant women participating in the (Maternal-Infant Research on Environmental Chemicals (MIREC) Study, urinary concentrations of BPA and TCS were measured in the first trimester by liquid chromatography-tandem mass spectrometry using isotope dilution. Blood pressure was measured during each trimester. Multinomial regression was performed to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) for the associations between these phenols and gestational hypertension and preeclampsia.Results: BPA urinary concentrations were similar according to hypertension status: the median (interquartile range) concentrations were 0.97 µg/L (0.40, 2.00), 1.10 µg/L (0.40, 1.90), and 0.80 µg/L (0.35, 1.70) for women with gestational hypertension, those with preeclampsia and normotensive women, respectively (p &amp;#61; 0.075). For TCS, the values were 10.04 µg/L (2.56, 76.26) for the group with gestational hypertension, 6.48 µg/L (1.48, 67.94) for those with preeclampsia and 8.56 µg/L (2.16, 67.35) for normotensive women (p &amp;#61; 0.559). Compared with the lowest tertile, BPA and TCS were not associated with gestational hypertension (aOR for BPA &amp;gt; 1.30 µg/L &amp;#61; 1.00; 95% CI: 0.54-1.81 and aOR for TCS &amp;gt; 32.6 µg/L &amp;#61; 1.41; 95% CI: 0.83-2.37) or preeclampsia (aOR for highest tertiles were 1.26; 95% CI: 0.53-2.97 and 0.68; 95% CI: 0.31-1.48, respectively). Conclusion: BPA and TCS urinary concentrations measured during the first trimester of pregnancy were not associated with gestational hypertension or preeclampsia. Additional studies are required to confirm our results.

Association of urinary concentrations of bisphenols with type 2 diabetes mellitus: A case-control study

Bisphenols, as synthetic chemicals, have been widely detected in environmental and human samples. Epidemiological studies have reported relationships between bisphenol A (BPA) and type 2 diabetes mellitus (T2DM), but results are inconsistent. Additionally, the associations between other bisphenols (i.e., the substitutes of BPA) with T2DM have been scarcely reported. A case-control study was conducted to examine the associations of urinary bisphenols with T2DM by investigating 8 bisphenols in urine samples of 251 T2DM cases and 251 controls and using different statistic models. Urinary bisphenol AF (BPAF) and bisphenol S (BPS) concentrations were significantly positively associated with T2DM in the log-transformed statistical models and adjusted odd ratios (ORs) were separately 4.95 [95% confidence interval (CI): 3.15, 7.79] and 1.73 (95% CI: 1.37, 2.18), which was consistent with the results in categorical models (OR = 2.03; 95% CI: 1.31, 3.15; p = 0.001 for BPAF; OR = 3.83; 95% CI: 2.37, 6.20; p < 0.001 for BPS). In addition, in the categorical models, elevated odds of T2DM were observed in the second BPA quartile (OR = 2.58; 95% CI: 1.38, 4.80) and the third quartile (OR = 1.89; 95% CI: 1.03, 3.46), but not in the fourth quartile, which reflected a nonlinear association between urinary BPA and T2DM. Similarly, only significant positive association with T2DM was found in the second quartile of the sum of bisphenols (OR = 2.07; 95% CI: 1.12, 3.82). In the sensitivity analyses, the associations of bisphenols with T2DM remained consistent except for BPAF in the categorical model. Our study suggested that several urinary bisphenols were positively associated with T2DM.

Disruption of neonatal cardiomyocyte physiology following exposure to bisphenol-a

Bisphenol chemicals are commonly used in the manufacturing of polycarbonate plastics, polyvinyl chloride plastics, resins, and thermal printing applications. Humans are inadvertently exposed to bisphenols through contact with consumer products and/or medical devices. Recent reports have shown a link between bisphenol-a (BPA) exposure and adverse cardiovascular outcomes; although these studies have been limited to adult subjects and models. Since cardiac physiology differs significantly between the developing and adult heart, we aimed to assess the impact of BPA exposure on cardiac function, using a neonatal cardiomyocyte model. Neonatal rat ventricular myocytes were monitored to assess cell viability, spontaneous beating rate, beat rate variability, and calcium-handling parameters in the presence of control or bisphenol-supplemented media. A range of doses were tested to mimic environmental exposure (10−9–10−8M), maximum clinical exposure (10−5M), and supraphysiological exposure levels (10−4M). Acute BPA exposure altered cardiomyocyte functionality, resulting in a slowed spontaneous beating rate and increased beat rate variability. BPA exposure also impaired intracellular calcium handling, resulting in diminished calcium transient amplitudes, prolonged calcium transient upstroke and duration time. Alterations in calcium handling also increased the propensity for alternans and skipped beats. Notably, the effect of BPA-treatment on calcium handling was partially reversible. Our data suggest that acute BPA exposure could precipitate secondary adverse effects on contractile performance and/or electrical alternans, both of which are dependent on intracellular calcium homeostasis.

Bisphenol A is not associated with a 5-year incidence of type 2 diabetes: a prospective nested case-control study.

The relationship between bisphenol A (BPA) and diabetes remains controversial. This study aims to investigate whether serum BPA level could predict the 5-year incidence of type 2 diabetes (T2D). A nested case-control study was performed among Chinese who participated in the environment, inflammation and metabolic diseases study (2008-2013). Of the 3510 subjects who were free of diabetes, 232 subjects developed diabetes during the 5-year follow-up. Cases and controls were matched for age and gender by a ratio of 1:1. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β) and insulin resistance (HOMA-IR). Participants were stratified into tertiles based on low, median and high baseline serum BPA levels. Regression models were used to analyze the relationship between serum BPA concentration and the incidence of T2D. At baseline, no significant difference in serum BPA concentration was observed between patients with T2D and controls [1.3 (0.3, 3.7) vs. 1.6 (0.4, 3.9)μmol/L, P=0.199]; serum BPA concentration was positively associated with fasting plasma glucose (r=0.27, P<0.001); however, neither HOMA-β nor HOMA-IR correlated with serum BPA concentration. During the follow-up, baseline BPA levels could not predict the 5-year T2D incidence, whether or not adjusted for the potential confounders such as body mass index and blood pressure. [Low BPA tertile was the reference, OR 0.66 (95% CI 0.30, 1.44) for median, OR 0.93 (95% CI 0.41, 2.13) for high.] CONCLUSION: BPA is not associated with a 5-year T2D incidence. These data do not support previous cross-sectional study that BPA exerted a detrimental effect on glucose metabolism.

High-throughput biomolecular interaction analysis probing by an array fluorescent biosensor platform

Interactions between biomolecules have been extensively investigated in versatile applications, such as biosensing, medical diagnosis and drug screening. In this study, an improved biomolecular interaction analysis probing with an integrated array fluorescent biosensor platform is proposed to overcome the limitations of surface plasmon resonance (SPR), such as a small number of reactions that can be simultaneously analysed and weak reusability of biospecific active surfaces. Reactions between biological molecules at twenty-four individual biosensing spots are monitored in real time by measuring the changes in fluorescence intensity excited by an evanescent wave field at a biospecific active surface. A sensor chip with the biospecific active surface is reusable with over 200 test cycles. The interaction between bisphenol A (BPA) and anti-BPA antibody is chosen as a paradigm to validate this assay. With a wide range of low to high concentrations of anti-BPA antibody, twenty-four response curves at the individual biosensing spots can be generated in real time and simultaneously provide further information about the interactions between antibody and surface-tethered antigen. This system is also characterised by its high-throughput cross-reactivity analysis between antigens and antibodies on the patterned waveguide with a shortened time-to-result.

Submicromolar bisphenol A induces proliferation and DNA damage in human hepatocyte cell lines in vitro and in juvenile rats in vivo

An association between bisphenol A (BPA) exposure and hepatic tumors was suggested, but the employment of high-dose levels raises questions about its relevance to human health. Here, we demonstrate that submicromolar concentrations of BPA induce the proliferation and DNA damage in human hepatocyte cell lines. In HepG2 and NKNT-3, undifferentiated and differentiated hepatocyte cell lines, respectively, submicromolar BPA concentrations promoted the cell proliferation, as indicated by enhanced DNA synthesis and elevated expression of cell-cycle proteins. At concentrations higher than 10 μM, these effects disappeared, reflecting a non-monotonic dose-response relationship. Notably, histone H2AX was activated following exposure to BPA, which is a sensitive marker of DNA damage. Importantly, proliferative foci and DNA damage were also observed in liver tissue of rats orally exposed to BPA at 0.5 mg/kg for 90 days, from juvenile age (postnatal day 9) through adulthood. Reactive oxygen species appeared to play a role in the BPA-induced proliferation and DNA damage, as evidenced by a partial reversal of both processes upon pretreatment with an antioxidant, N-acetylcysteine. Collectively, these results demonstrate that submicromolar BPA concentrations induce the DNA damage and promote the cell proliferation in the liver, which may support its role as a risk factor for hepatocarcinogenicity.

Bisphenol A and reproductive hormones and cortisol in peripubertal boys: The INMA-Granada cohort

IntroductionBisphenol A (BPA) is a well-known endocrine disrupting compound. Although several studies have investigated the effect of BPA exposure and reproductive hormones in humans, results have been inconsistent. ObjectiveTo explore the cross-sectional relationship between bisphenol A (BPA) exposure and reproductive hormones/cortisol among peripubertal boys. Material and methodsUrinary BPA and serum hormones were assessed in 172 boys belonging to the INMA “Environment and Childhood” Granada birth cohort in their follow-up at 9–11years of age. BPA concentrations were quantified by liquid chromatography-mass spectrometry, and levels of serum total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol were measured by electrochemiluminescence immunoassay. Result(s)After adjustment for confounders, linear regression models showed that each natural-log unit increase in urinary BPA concentrations was associated with a 19% increase in geometric mean (GM) serum TT levels, and a 16% decrease in GM serum cortisol levels. When urinary BPA concentrations were categorized in tertiles, boys in the 3rd tertile showed 49% higher TT levels and 23% lower cortisol concentrations compared to boys in the 1st tertile. Additionally, urinary BPA concentrations were also significantly associated with higher TT:LH and TT:cortisol ratios, but not with serum LH or FSH levels. Conclusion(s)Our results suggest the possible endocrine disrupting potential of BPA during this important period of development. Although action at the testis or pituitary cannot be ruled out, our findings are compatible with a possible involvement of BPA at the adrenal gland, resulting in a differential production of androgens/cortisol. However, given the cross-sectional design of our study, the heterogeneous results reported in the literature, and the scant experimental research on BPA effects at the adrenal gland, the present findings should be interpreted with caution.

Endocrine Disruptors: A Potential Risk Factor for Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) has increased dramatically in the past 20 years together with the obesity epidemic. Mirroring the increase in incidence of GDM is increasing use of endocrine disrupting chemicals (EDCs). EDCs are structurally similar to endogenous hormones and interfere with synthesis, secretion, activity, or elimination of natural hormones, resulting in adverse health effects, including diabetes, obesity, developmental disorders, etc. Although the association between bisphenol A (BPA), a well-studied EDC, and type 2 diabetes has been repeatedly investigated in epidemiological and animal studies, there is a dearth of studies examining EDCs and GDM. In fact, the impact of environmental toxins on perinatal health outcomes has largely been overlooked.Recognizing this research gap, the American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, and International Federation of Gynecology and Obstetrics recently joined leading scientists and clinicians in a call for action to prioritize research in the consequences of exposure to toxic environmental agents on women's health. Evidence is emerging to suggest signaling molecules and EDCs are involved in the control of microRNA (miRNA) expression in trophoblast cells. We reviewed existing scientific evidence of EDCs as a risk factor for GDM as well as the potential role of miRNA in this association.

A study of the influence on diabetes of free and conjugated bisphenol A concentrations in urine: Development of a simple microextraction procedure using gas chromatography–mass spectrometry

The association between bisphenol A (BPA) exposure and adult health status is examined by measuring the urinary BPA concentration using a miniaturized technique based on dispersive liquid-liquid microextraction (DLLME) in combination with gas chromatography-mass spectrometry (GC–MS). Both the free bioactive and the glucuronide conjugated forms of BPA were measured, the glucuronide form usually being predominant. The main analogs of BPA, including bisphenol Z (BPZ), bisphenol F (BPF) and biphenol (BP) were also determined. Several parameters affecting enzymatic hydrolysis, derivatization by in-situ acetylation and the DLLME stages were carefully optimized by means of multivariate designs. DLLME parameters were 2mL urine, 1mL acetone and 100μL chloroform, and hydrolysis was performed using β-glucuronidase and sulfatase at pH 5. No matrix effect was observed and quantification was carried out by aqueous calibration with a surrogate standard. Detection limits were in the range 0.01–0.04ngmL−1. The intraday and interday precisions were lower than 11% in terms of relative standard deviation. Satisfactory values for all compounds were obtained in recovery studies (92–117%) at two concentration levels. Other bisphenols (BPF, BPZ and BP) were not detected in the urine samples, while BPA was the only bisphenol detected in the free form (creatinine adjusted) at concentration levels ranging from the detection limit to 15.9ngg−1, and total BPA was detected at concentrations ranging from 0.46 to 24.5ngg−1 levels. A comparison of the BPA content for both groups of patients revealed that slightly higher mean values were obtained for both free BPA and total BPA for diabetic patients, than for non-diabetic patients. However, a statistical comparison of the contents of BPA revealed that there were no significant differences. The procedure was validated using a certified reference material.

Diabetes Genetic Risk Score Modifies Effect of Bisphenol A Exposure on Deterioration in Glucose Metabolism.

Epidemiology studies showed inconsistent results regarding the relationship between bisphenol A (BPA) exposure and risk of type 2 diabetes (T2D). This study sought to prospectively investigate associations of BPA with incident T2D risk and the longitudinal changes in glycemic traits, particularly examining the interaction between gene and BPA exposure on the associations. A community-based study was conducted at baseline in 2009, including 2209 nondiabetic middle-age and elderly subjects followed for 4 y. Urinary BPA levels were measured at baseline. A genetic risk score (GRS) based on 34 T2D common variants that identified and validated in East Asians was created. Incident T2D was defined according to the 1999 World Health Organization criteria. Fasting (FPG) and 2-h post-loading plasma glucose were measured at baseline and followup. Multivariable logistic regression analysis demonstrated no significant association of risk of incident T2D with BPA while with increase in the weighted T2D-GRS (odds ratio, 1.89; 95% confidence interval, 1.31-2.72 for each 10-point increment). Similar results were found in 4-y changes of FPG and 2-h post-loading plasma glucose. The GRS modified the effect of BPA exposure on 4-y changes in FPG (P for interaction = .01). Each 1 unit of Log_BPA was associated with 0.1 mmol/L increase in FPG (P = .007) in the highest quartile of GRS; no associations were found in the lower three quartiles of GRS. The T2D genetic susceptibility significantly modulated the association of BPA exposure with longitudinal increase in FPG levels.

Influence of Bisphenol A on Thyroid Volume and Structure Independent of Iodine in School Children.

BackgroundAlthough several studies have evaluated the relationship between bisphenol A (BPA) and thyroid functions, their results are not entirely consistent. Little is known about BPA in relation to thyroid volume and structure.MethodsWe examined the association of BPA with thyroid volume and thyroid nodules using data from 718 Chinese children living in the East Coast of China in 2012. First morning urine samples were collected for the determination of urinary BPA, creatinine, and urinary iodine concentrations (UIC). Thyroid volume (TV) and nodules were assessed by thyroid ultrasonography.ResultsThe median of TV was 3.14ml. 459(63.9%) children took iodized salt at home and the median of UIC was 159μg/l. BPA was detected in 99.9% of the urine samples and the medians for boys and girls were 2.64 and 2.35μg/g creatinine, respectively. Of all participants 14.0% had thyroid nodules. Urinary BPA concentration was inversely associated with thyroid volume (β = -0.033, 95% CI: -0.053, -0.013) and the risk for multiple nodules (OR = 0.78; 95% CI: 0.63, 0.97). The associations above were similar for children who consumed iodized salt and those consumed non-iodized salt.ConclusionsThe data suggest that BPA may be one of the influencing factors for TV and thyroid nodules and its effects are independent of iodine nutrition status in children.