The Role of Endocrine Disrupting Chemicals in Gestation and Pregnancy Outcomes.

Endocrine disrupting chemicals (EDCs) are exogenous substances widely disseminated both in the environment and in daily-life products which can interfere with the regulation and function of the endocrine system. These substances have gradually entered the food chain, being frequently found in human blood and urine samples. This becomes a particularly serious issue when they reach vulnerable populations such as pregnant women, whose hormones are more unstable and vulnerable to EDCs. The proper formation and activity of the placenta, and therefore embryonic development, may get seriously affected by the presence of these chemicals, augmenting the risk of several pregnancy complications, including intrauterine growth restriction, preterm birth, preeclampsia, and gestational diabetes mellitus, among others. Additionally, some of them also exert a detrimental impact on fertility, thus hindering the reproductive process from the beginning. In several cases, EDCs even induce cross-generational effects, inherited by future generations through epigenetic mechanisms. These are the reasons why a proper understanding of the reproductive and gestational alterations derived from these substances is needed, along with efforts to establish regulations and preventive measures in order to avoid exposition (especially during this particular stage of life).

Levels of Bisphenol A and its analogs in nails, saliva, and urine of children: a case control study.

Introduction: A growing number of studies link the increase in overweight/obesity worldwide to exposure to certain environmental chemical pollutants that display obesogenic activity (obesogens). Since exposure to obesogens during the first stages of life has been shown to have a more intense and pronounced effect at lower doses, it is imperative to study their possible effects in childhood. The objective here was to study the association of Bisphenol A (BPA) and 11 BPA analogs in children, using three biological matrices (nails, saliva and urine), and overweight and obesity (n = 160). Methods: In this case-control study, 59 overweight/obese children and 101 controls were included. The measuring of Bisphenols in the matrices was carried out by ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). Logistic regression was used to study the association between overweight/obesity and Bisphenol exposure. Results: The results suggested that BPF in nails is associated with overweight/ obesity in children (OR:4.87; p = 0.020). In saliva, however, the highest detected concentrations of BPAF presented an inverse association (OR: 0.06; p = 0.010) with overweight/obesity. No associations of statistical significance were detected between exposure to BPA or its other analogs and overweight/obesity in any of the biological matrices.

Presence of Parabens in Different Children Biological Matrices and Its Relationship with Body Mass Index.

Parabens have been accepted almost worldwide as preservatives by the cosmetic, food, and pharmaceutical industries. Since epidemiological evidence of the obesogenic activity of parabens is weak, the aim of this study was to investigate the association between parabens exposure and childhood obesity. Four parabens (methylparaben/MetPB, ethylparaben/EthPB, propylparaben/PropPB, and butylparaben/ButPB) were measured in 160 children's bodies between 6 and 12 years of age. Parabens measurements were performed with ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Logistic regression was used to evaluate risk factors for elevated body weight associated with paraben exposure. No significant relation was detected between children's body weight and the presence of parabens in the samples. This study confirmed the omnipresence of parabens in children's bodies. Our results could be a basis for future research about the effect of parabens on childhood body weight using nails as a biomarker due to the ease of its collection and its non-invasive character.

Improved method for the determination of endocrine-disrupting chemicals in urine of school-age children using microliquid-liquid extraction and UHPLC-MS/MS.

The presence of endocrine-disrupting chemicals in our daily life is increasing every day and, by extension, human exposure and the consequences thereof. Among these substances are bisphenols and parabens. Urine is used to analyze the exposure. The determination of 12 bisphenol homologues and 6 parabens is proposed. A procedure based on a method previously developed by our research group in 2014 is improved. The extraction yield is higher, because the new protocol is 5 times more efficient. Also, a comparison between calibration with pure standards and matrix calibration, to calculate the matrix effect, was also made. A high grade of matrix effect for all analytes was observed. In terms of validation, the limits of detection (LOD) were between 0.03 and 0.3 ng mL-1 and limits of quantification (LOQ) 0.1 to 1.0 ng mL-1, respectively, and the recovery is higher than 86.4% and lower than 113.6%, with a RSD lower than 13.5% in all cases. A methodology for accurate and sensitive quantification of bisphenol homologues together with parabens in human urine using UHPLC-MS/MS was developed. The method was successfully applied to 30 urine samples from children.

Role of endocrine disrupting chemicals in children's neurodevelopment.

Environmental stressors, like endocrine disrupting chemicals (EDC), are considered important contributors to the increased rates of neurodevelopmental dysfunctions. Considering the cumulative research on adverse neurodevelopmental effects associated with prenatal exposure to EDC, the purpose of this study was to review the available limited literature about the effects of postnatal exposure to EDC on child neurodevelopment and behaviour. Despite widespread children's exposure to EDC, there are a limited number of epidemiological studies on the association of this exposure with neurodevelopmental disorders, in particular in the postnatal period. The available research suggests that postnatal EDC exposure is related to adverse neurobehavioral outcomes in children; however the underlying mechanisms of action remain unclear. Timing of exposure is a key factor determining potential neurodevelopmental consequences, hence studying the impact of multiple EDC co-exposure in different vulnerable life periods could guide the identification of sensitive subpopulations. Most of the reviewed studies did not take into account sex differences in the EDC effects on children neurodevelopment. We believe that the inclusion of sex in the study design should be considered as the role of EDC on children neurodevelopment are likely sex-specific and should be taken into consideration when determining susceptibility and potential mechanisms of action.

Effects of genetic polymorphisms in body mass index according to dietary exposure to bisphenols and parabens.

A growing body of evidence supports that more than 900 single nucleotide polymorphisms (SNPs) and exposure to endocrine disrupting chemicals, such as bisphenols and parabens, are important contributors to the development of obesity. The aim of this study was to evaluate the way in which fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs9436303 variants contribute to variability in body mass index (BMI) according to estimated dietary exposure of bisphenols and parabens. This cross-sectional study included 101 Spanish participants (16-24 years). SNP genotyping assays were performed through quantitative PCRs (qPCRs) using Taqman® probes. Dietary exposure to bisphenols and parabens was calculated from food frequency questionnaire and chemical determination in food samples by ultra-high performance liquid chromatography-tandem mass spectrometry system. Linear regression models were conducted to address the association of genetic variants and BMI according to levels of bisphenols/parabens exposure. Risk G allele of LEPR rs9436303 was significantly positively associated with BMI (exp (ß) = 1.20, 95% CI: 1.04-1.38, p = 0.011). In participants highly exposed to bisphenols, the LEPR rs9436303 G allele was related to a significant increased BMI (exp (ß) = 1.27, 95% CI: 1.03-1.57, p = 0.024). A more relevant trend was observed with high exposure to parabens (exp (ß) = 1.33, 95% CI: 1.08-1.63, p = 0.009). We provide the first evidence that interaction between LEPR polymorphism and dietary intake of bisphenols and parabens may be responsible for an increased BMI, suggesting a potential effect in obesity. Moreover, we proposed LEPR rs9436303 as a genetic marker of susceptibility to excess weight induced by exposure.

Factors Associated with Exposure to Dietary Bisphenols in Adolescents.

Obesogenic endocrine-disrupting chemicals, such as bisphenol A (BPA) and its analogue bisphenol S (BPS), seem to play an important role in the development of obesity, although contradictory results have been reported. The aim of the present study was to conduct a gender analysis of the factors associated with exposure to dietary bisphenols in 585 Spanish adolescents. Dietary BPA and BPS exposure was assessed using a food frequency questionnaire. Foods and macronutrients accounting for more than 95% of energy intake were selected for analysis. Stepwise regression was used to estimate the foods that most contributed to dietary bisphenol exposure in the sample. Gender-related factors associated with greater dietary bisphenol exposure were evaluated using multivariate logistic regression models. Canned tuna was the main dietary source of BPA and BPS in both adolescent boys and girls. Overweight/obese girls showed a higher risk of high dietary exposure to BPA (odds ratio (OR): 3.38, 95% confidence interval (CI): 1.25-9.07) and total bisphenols (OR: 2.81, 95% CI: 1.03-7.67) in comparison with girls with a BMI lower than 25 kg/m2. Present results indicate a positive association of dietary exposure to both total bisphenols and BPA with being overweight/obese in adolescent girls.

Dietary exposure to parabens and body mass index in an adolescent Spanish population.

Parabens are alkyl esters of p-hydroxybenzoic acid which are extensively used in cosmetics, pharmaceuticals and foodstuffs due to their antimicrobial properties. The most commonly used parabens are methyl-(MeP), ethyl-(EtP), propyl-(PrP) and butyl-(BuP) paraben. Most human exposure to parabens is achieved through the consumption of food or pharmaceutical products and the use of personal care products. However, studies on dietary parabens exposure and the associated factors are very scarce. The main aim of the present study was to explore factors associated with dietary exposure to parabens in Spanish adolescents according to gender. Dietary data and anthropometric measures were collected from 585 adolescents (53.4% boys) aged 12-16 years. Parabens exposure through diet was assessed using a food frequency questionnaire with food products providing more than 95% of energy and macronutrient intake being included in analysis. Stepwise regression was used to identify the foods that most contributed to parabens intake. Logistic regression was used to evaluate factors predicting higher dietary exposure to parabens. The main contributors to dietary MeP, EtP, PrP and BuP exposure in adolescent boys were eggs (41.9%), canned tuna (46.4%), bakery and baked goods products (57.3%) and pineapple (61.1%). In adolescent girls, the main contributors were apples and pears (35.3%), canned tuna (42.1%), bakery and baked goods products (55.1%) and olives (62.1%). Overweight/obese girls were more likely to belong to the highest tertile of overall parabens intake (odds ratio [OR]: 3.32; 95% confidence interval [95% CI]: 1.21-9.15) and MeP (OR: 3.05; 95% CI: 1.14-8.12) than those with a body mass index lower than 25 kg/m2. These findings suggest a positive association between dietary exposure to parabens and overweight/obesity in adolescent girls.

Metabolic pathways, alterations in miRNAs expression and effects of genetic polymorphisms of bisphenol a analogues: A systematic review.

Bisphenol A (BPA) is one of the most common endocrine disruptors found in the environment and its harmful health effects in humans and wildlife have been extensively reported One of the main aims of this review was to examine the metabolic pathways of BPA and BPA substitutes and the endocrine disrupting properties of their metabolites. According to the available literature, phase I and phase II metabolic reactions play an important role in the detoxification process of bisphenols (BPs), but their metabolism can also lead to the formation of highly reactive metabolites. The second part of this work addresses the associations between exposure to BPA and its analogues with the alterations in miRNAs expression and the effects of single nucleotide polymorphisms (SNPs). Available scientific evidence shows that BPs can dysregulate the expression of several miRNAs, and in turn, these miRNAs could be considered as epigenetic biomarkers to prevent the development of a variety of BP-mediated diseases. Interestingly, genetic polymorphisms are able to modify the relationship of BPA exposure with the risk of adverse health effects, suggesting that interindividual genetic differences modulate the susceptibility to the effects of environmental contaminants.

Presence of Parabens and Bisphenols in Food Commonly Consumed in Spain.

Given the widespread use of bisphenols and parabens in consumer products, the assessment of their intake is crucial and represents the first step towards the assessment of the potential risks that these compounds may pose to human health. In the present study, a total of 98 samples of food items commonly consumed by the Spanish population were collected from different national supermarkets and grocery stores for the determination of parabens and bisphenols. Our analysis demonstrated that 56 of the 98 food samples contained detectable levels of parabens with limits of quantification (LOQ) between 0.4 and 0.9 ng g-1. The total concentration of parabens (sum of four parabens: ∑parabens) ranged from below the LOQ to 281.7 ng g-1, with a mean value of 73.86 ng g-1. A total of 52% of the samples showed detectable concentrations of bisphenols. Bisphenol A (BPA) was the most frequently detected bisphenol in the food samples analysed, followed by bisphenol S (BPS) and bisphenol E (BPE). Bisphenol AF (BPAF), bisphenol B (BPB) and bisphenol P (BPP) were not found in any of the analysed samples. LOQ for these bisphenols were between 0.4 and 4.0 ng g-1.

Endobolome, a New Concept for Determining the Influence of Microbiota Disrupting Chemicals (MDC) in Relation to Specific Endocrine Pathogenesis.

Endogenous steroid hormones and Endocrine Disrupting Chemicals (EDC) interact with gut microbiota through different pathways. We suggest the use of the term "endobolome" when referring to the group of gut microbiota genes and pathways involved in the metabolism of steroid hormones and EDC. States of dysbiosis and reduced diversity of the gut microbiota may impact and modify the endobolome resulting at long-term in the development of certain pathophysiological conditions. The endobolome might play a central role in the gut microbiota as seen by the amount of potentially endobolome-mediated diseases and thereby it can be considered an useful diagnostic tool and therapeutic target for future functional research strategies that envisage the use of next generation of probiotics. In addition, we propose that EDC and other xenobiotics that alter the gut microbial composition and its metabolic capacities should be categorized into a subgroup termed "microbiota disrupting chemicals" (MDC). This will help to distinguish the role of contaminants from other microbiota natural modifiers such as those contained or released from diet, environment, physical activity and stress. These MDC might have the ability to promote specific changes in the microbiota that can ultimately result in common intestinal and chronic or long-term systemic diseases in the host. The risk of developing certain disorders associated with gut microbiota changes should be established by determining both the effects of the MDC on gut microbiota and the impact of microbiota changes on chemicals metabolism and host susceptibility. In any case, further animal controlled experiments, clinical trials and large epidemiological studies are required in order to establish the concatenated impact of the MDC-microbiota-host health axis.

Endocrine Disruptors in Food: Impact on Gut Microbiota and Metabolic Diseases.

Endocrine disruptors (EDCs) have been associated with the increased incidence of metabolic disorders. In this work, we conducted a systematic review of the literature in order to identify the current knowledge of the interactions between EDCs in food, the gut microbiota, and metabolic disorders in order to shed light on this complex triad. Exposure to EDCs induces a series of changes including microbial dysbiosis and the induction of xenobiotic pathways and associated genes, enzymes, and metabolites involved in EDC metabolism. The products and by-products released following the microbial metabolism of EDCs can be taken up by the host; therefore, changes in the composition of the microbiota and in the production of microbial metabolites could have a major impact on host metabolism and the development of diseases. The remediation of EDC-induced changes in the gut microbiota might represent an alternative course for the treatment and prevention of metabolic diseases.

Bisphenol A Analogues in Food and Their Hormonal and Obesogenic Effects: A Review.

Bisphenol A (BPA) is the most well-known compound from the bisphenol family. As BPA has recently come under pressure, it is being replaced by compounds very similar in structure, but data on the occurrence of these BPA analogues in food and human matrices are limited. The main objective of this work was to investigate human exposure to BPA and analogues and the associated health effects. We performed a literature review of the available research made in humans, in in vivo and in vitro tests. The findings support the idea that exposure to BPA analogues may have an impact on human health, especially in terms of obesity and other adverse health effects in children.