Environmental Exposures and Pediatric Cardiology: A Scientific Statement From the American Heart Association.

Environmental toxicants and pollutants are causes of adverse health consequences, including well-established associations between environmental exposures and cardiovascular diseases. Environmental degradation is widely prevalent and has a long latency period between exposure and health outcome, potentially placing a large number of individuals at risk of these health consequences. Emerging evidence suggests that environmental exposures in early life may be key risk factors for cardiovascular conditions across the life span. Children are a particularly sensitive population for the detrimental effects of environmental toxicants and pollutants given the long-term cumulative effects of early-life exposures on health outcomes, including congenital heart disease, acquired cardiac diseases, and accumulation of cardiovascular disease risk factors. This scientific statement highlights representative examples for each of these cardiovascular disease subtypes and their determinants, focusing specifically on the associations between climate change and congenital heart disease, airborne particulate matter and Kawasaki disease, blood lead levels and blood pressure, and endocrine-disrupting chemicals with cardiometabolic risk factors. Because children are particularly dependent on their caregivers to address their health concerns, this scientific statement highlights the need for clinicians, research scientists, and policymakers to focus more on the linkages of environmental exposures with cardiovascular conditions in children and adolescents.

A review of cumulative toxic effects of environmental endocrine disruptors on the zebrafish immune system: Characterization methods, toxic effects and mechanisms.

Environmental endocrine disrupting chemicals (EDCs), are a type of exogenous organic pollutants, are ubiquitous in natural aquatic environments. Currently, in addition to neurological, endocrine, developmental and reproductive toxicity, ecotoxicology studies on immunotoxicity are receiving increasing attention. In this review, the composition of immune system of zebrafish, the common indicators of immunotoxicity, the immunotoxicity of EDCs and their molecular mechanism were summarized. We reviewed the immunotoxicity of EDCs on zebrafish mainly in terms of immune organs, immunocytes, immune molecules and immune functions, meanwhile, the possible molecular mechanisms driving these effects were elucidated in terms of endocrine disruption, dysregulation of signaling pathways, and oxidative damage. Hopefully, this review will provide a reference for further investigation of the immunotoxicity of EDCs.

Self-assembled mesoporous silica decorated with biogenic carbon dot nanospheres hybrid nanomaterial for efficient removal of aqueous Methoxy-DDT via a Short-Bed Adsorption column technique.

Methoxy-DDT is an organochlorine pesticide extensively used in agricultural practices as a DDT substitute. Methoxy-DDT has been found and quantified in several investigations in groundwater, drinking water, sediment, and various biota. Therefore, designing efficient and cost-effective adsorbents for removing methoxy-DDT is vital. In this work, we embedded Ficus benghalensis L. derived carbon dots (CDs) in mesoporous silica (MS) to fabricate MS-CDs nanohybrid material. MS-CDs nanohybrid exhibited remarkable selectivity and removal efficiency towards methoxy-DDT, outperforming other endocrine disruptors. Parameters for industrial-scale fixed-bed adsorption columns, such as bed capacity, length, and breakthrough times, were analyzed. The kinetic study revealed that pseudo-second-order (PSO) adsorption and isotherm analysis confirmed the Langmuir model as the best fit. Small bed adsorption (SBA) column analysis was carried out using spiked Yamuna river water, and the breakthrough curves were demonstrated by varying MS-CDs bed height. The maximum adsorption capacity obtained for methoxy-DDT was 17.16 mg/g at breakthrough and 49.98 mg/g at exhaustion. The adsorbent showed 86.53% removal efficiency in the 5th cycle, demonstrating good reusability. These results indicate that the developed material MS-CDs-based organic sphere is an effective adsorbent for aqueous methoxy-DDT adsorption and can be applied to wastewater treatment.

Farming activity and risk of treated thyroid disorders: Insights from the TRACTOR project, a nationwide cohort study.

BACKGROUND: Epidemiological data regarding thyroid diseases are lacking, in particular for occupationally exposed populations. OBJECTIVES: To compare the risk of hypothyroidism and hyperthyroidism between farming activities within the complete population of French farm managers (FMs). METHODS: Digital health data from retrospective administrative databases, including insurance claims and electronic health/medical records, was employed. This cohort data spanned the entirety of French farm managers (FMs) who had undertaken work at least once from 2002 to 2016. Survival analysis with the time to initial medication reimbursement as timescale was used to examine the association (hazard ratio, HR) between 26 specific farming activities and both treated hypothyroidism and hyperthyroidism. A distinct model was developed for each farming activity, comparing FMs who had never engaged in the specific farming activity between 2002 and 2016 with those who had. All analyses were adjusted for potential confounders (e.g., age), and sensitivity analyses were conducted. RESULTS: Among 1088561 FMs (mean age 46.6 [SD 14.1]; 31% females), there were 31834 hypothyroidism cases (75% females) and 620 hyperthyroidism cases (67% females), respectively. The highest risks were observed for cattle activities for both hyperthyroidism (HR ranging from 1.75 to 2.42) and hypothyroidism (HR ranging from 1.41 to 1.44). For hypothyroidism, higher risks were also observed for several animal farming activities (pig, poultry, and rabbit), as well as fruit arboriculture (HR = 1.22 [1.14-1.31]). The lowest risks were observed for activities involving horses. Sex differences in the risk of hypothyroidism were observed for eight activities, with the risk being higher for males (HR = 1.09 [1.01-1.20]) than females in viticulture (HR = 0.97 [0.93-1.00]). The risk of hyperthyroidism was two times higher for male dairy farmers than females. DISCUSSION: Our findings offer a comprehensive overview of thyroid disease risks within the FM community. Thyroid ailments might not stem from a single cause but likely arise from the combined effects of various causal agents and triggering factors (agricultural exposome). Further investigation into distinct farming activities-especially those involving cattle-is essential to pinpoint potential risk factors that could enhance thyroid disease monitoring in agriculture.

Bisphenol A and cardiometabolic risk in adolescents: Data from the Generation XXI cohort.

BACKGROUND AND AIMS: Bisphenol A (BPA), an endocrine disruptor widely used in food contact materials, has been linked to a worse health profile. This study intends to estimate the association between BPA exposure and cardiometabolic patterns at adolescence. METHODS AND RESULTS: Data from the Portuguese population-based birth cohort Generation XXI at the age of 13 were used (n = 2386 providing 3-day food diaries and fasting blood samples). BPA exposure was measured in 24-h urine from a subsample (n = 206) and then predicted in all participants using a random forest method and considering dietary intake from diaries. Three cardiometabolic patterns were identified (normal, modified lipid profile and higher cardiometabolic risk) using a probabilistic Gaussian mixture model. Multinomial regression models were applied to associate BPA exposure (lower, medium, higher) and cardiometabolic patterns, adjusting for confounders. The median BPA exposure was 1532 ng/d, corresponding to 29.4 ng/kg/d. Adolescents higher exposed to BPA (compared to medium and lower levels) had higher BMI z-score (kg/m2) (0.68 vs. 0.39 and 0.52, respectively; p = 0.008), higher levels of body fat (kg) (16.3 vs. 13.8 and 14.6, respectively; p = 0.002), waist circumference (76.2 vs. 73.7 and 74.9, respectively; p = 0.026), insulinemia (ug/mL) (14.1 vs. 12.7 and 13.1, respectively; p = 0.039) and triglyceridemia (mg/dL) (72.7 vs. 66.1 and 66.5, respectively; p = 0.030). After adjustment, a significant association between higher BPA and a higher cardiometabolic risk pattern was observed (OR: 2.55; 95%CI: 1.41, 4.63). CONCLUSION: Higher BPA exposure was associated with a higher cardiometabolic risk pattern in adolescents, evidencing the role of food contaminants in health.

Endocrine Disruptors and Metabolic Changes: Impact on Puberty Control.

OBJECTIVE: This study aims to explore the significant impact of environmental chemicals on disease development, focusing on their role in developing metabolic and endocrine diseases. The objective is to understand how these chemicals contribute to the increasing prevalence of precocious puberty, considering various factors, including epigenetic changes, lifestyle, and emotional disturbances. METHODS: The study employs a comprehensive review of descriptive observational studies in both human and animal models to identify a degree of causality between exposure to environmental chemicals and disease development, specifically focusing on endocrine disruption. Due to ethical constraints, direct causation studies in human subjects are not feasible; therefore, the research relies on accumulated observational data. RESULTS: Puberty is a crucial life period with marked physiological and psychological changes. The age at which sexual characteristics develop is changing in many regions. The findings indicate a correlation between exposure to endocrine-disrupting chemicals and the early onset of puberty. These chemicals have been shown to interfere with normal hormonal processes, particularly during critical developmental stages such as adolescence. The research also highlights the interaction of these chemical exposures with other factors, including nutritional history, social and lifestyle changes, and emotional stress, which together contribute to the prevalence of precocious puberty. CONCLUSION: Environmental chemicals significantly contribute to the development of certain metabolic and endocrine diseases, particularly in the rising incidence of precocious puberty. Although the evidence is mainly observational, it adequately justifies regulatory actions to reduce exposure risks. Furthermore, these findings highlight the urgent need for more research on the epigenetic effects of these chemicals and their wider impact on human health, especially during vital developmental periods.

In silico analysis of endocrine-disrupting potential of triclosan, bisphenol A, and their analogs and derivatives.

Owning to the increasing body of evidence about the ubiquitous exposure to endocrine disruptors (EDCs), particularly bisphenol A (BPA), and associated health effects, BPA has been gradually substituted with insufficiently tested structural analogs. The unmanaged excessive use of antimicrobial agents such as triclosan (TCS) during the COVID-19 outbreak has also raised concerns about its possible interferences with hormonal functions. The similarity of BPA and estradiol, as well as TCS and non-steroidal estrogens, imply that endocrine-disrupting properties of their analogs could be predicted based on the chemical structure. Hence, this study aimed to evaluate the endocrine-disrupting potential of BPA substitutes as well as TCS derivatives and degradation/biotransformation metabolites, in comparison to BPA and TCS based on their molecular properties, computational predictions of pharmacokinetics and binding affinities to nuclear receptors. Based on the obtained results several under-researched BPA analogs exhibited higher binding affinities for nuclear receptors than BPA. Notable analogs included compounds detected in receipts (DD-70, BTUM-70, TGSA, and BisOPP-A), along with a flame retardant, BDP. The possible health hazards linked to exposure to TCS and its mono-hydroxylated metabolites were also found. Further research is needed in order to elucidate the health impacts of these compounds and promote better regulation practices.

Endocrine disruption of adipose physiology: Screening in SGBS cells.

The increasing use of industrial chemicals has raised concerns regarding exposure to endocrine-disrupting chemicals (EDCs), which interfere with developmental, reproductive and metabolic processes. Of particular concern is their interaction with adipose tissue, a vital component of the endocrine system regulating metabolic and hormonal functions. The SGBS (Simpson Golabi Behmel Syndrome) cell line, a well-established human-relevant model for adipocyte research, closely mimics native adipocytes' properties. It responds to hormonal stimuli, undergoes adipogenesis and has been successfully used to study the impact of EDCs on adipose biology. In this study, we screened human exposure-relevant doses of various EDCs on the SGBS cell line to investigate their effects on viability, lipid accumulation and adipogenesis-related protein expression. Submicromolar doses were generally well tolerated; however, at higher doses, EDCs compromised cell viability, with cadmium chloride (CdCl2) showing the most pronounced effects. Intracellular lipid levels remained unaffected by EDCs, except for tributyltin (TBT), used as a positive control, which induced a significant increase. Analysis of adipogenesis-related protein expression revealed several effects, including downregulation of fatty acid-binding protein 4 (FABP4) by dibutyl phthalate, upregulation by CdCl2 and downregulation of perilipin 1 and FABP4 by perfluorooctanoic acid. Additionally, TBT induced dose-dependent upregulation of C/EBPα, perilipin 1 and FABP4 protein expression. These findings underscore the importance of employing appropriate models to study EDC-adipocyte interactions. Conclusions from this research could guide strategies to reduce the negative impacts of EDC exposure on adipose tissue.

Mixed probiotics modulated gut microbiota to improve spermatogenesis in bisphenol A-exposed male mice.

Bisphenol A (BPA), an environmental endocrine disruptor (EDC), has been implicated in impairing intestinal and male reproductive dysfunction. The efficacy of gut microbiota modulation for BPA-exposed testicular dysfunction has yet to be verified through research. Therefore, this study explored the potential of mixed probiotics in restoring spermatogenesis damage through the gut-testis axis under BPA exposure. We selected two probiotics strains (Lactobacillus rhamnosus and Lactobacillus plantarum) with BPA removal properties in vitro and the BPA-exposed male mice model was established. The probiotics mixture effectively reduced BPA residue in the gut, serum, and testis in mice. Through 16 S rDNA-seq and metabolomics sequencing, we uncovered that vitamin D metabolism and bile acid levels in the gut was abolished under BPA exposure. This perturbation was linked to an increased abundance of Faecalibaculum and decreased abundance of Lachnospiraceae_NK4A136_group and Ligilactobacillus. The probiotics mixture restored this balance, enhancing intestinal barrier function and reducing oxidative stress. This improvement was accompanied by a restored balance of short-chain fatty acids (SCFAs). Remarkably, the probiotics ameliorated testicular dysfunction by repairing structures of seminiferous tubules and reversing arrested spermiogenesis. Further, the probiotics mixture enhanced testosterone-driven increases in spermatogonial stem cells and all stages of sperm cells. Testicular transcriptome profiling linked these improvements to fatty acid degradation and peroxisome pathways. These findings suggest a significant interplay between spermatogenesis and gut microbiota, demonstrating that probiotic intake could be a viable strategy for combating male subfertility issues caused by BPA exposure.

Bisphenol A and chlorinated derivatives of bisphenol A assessment in end stage renal disease patients: Impact of dialysis therapy.

Patients with end stage kidney disease treated by dialysis (ESKDD) process dialysis sessions to remove molecules usually excreted by kidneys. However, dialysis therapy could also contribute to endocrine disruptors (ED) burden. Indeed, materials like dialyzer filters, ultrapure dialysate and replacement fluid could exposed ESKDD patients to Bisphenol A (BPA) and chlorinated derivatives of BPA (ClxBPAs). Thus, our aim was to compare BPA and ClxBPAs exposure between ESKDD patients, patients with stage 5 chronic kidney disease (CKD5) not dialyzed and healthy volunteers. Then we describe the impact of a single dialysis session, according to dialysis modalities (hemodialysis therapy (HD) versus online hemodiafiltration therapy (HDF)) and materials used with pre-post BPA and ClxBPAs concentrations. The plasma levels of BPA and four ClxBPAs, were assessed for 64 ESKDD patients in pre and post dialysis samples (32 treated by HD and 32 treated by HDF) in 36 CKD5 patients and in 24 healthy volunteers. BPA plasma concentrations were 22.5 times higher for ESKDD patients in pre-dialysis samples versus healthy volunteers (2.208 ± 5.525 ng/mL versus 0.098 ± 0.169 ng/mL) (p < 0.001). BPA plasma concentrations were 16 times higher for CKD5 patients versus healthy volunteers, but it was not significant (1.606 ± 3.230 ng/mL versus 0.098 ± 0.169 ng/mL) (p > 0.05). BPA plasma concentrations for ESKDD patients in pre-dialysis samples were 1.4 times higher versus CKD5 patients (2.208 ± 5.525 ng/mL versus 1.606 ± 3.230 ng/mL) (p < 0.001). For healthy volunteers, ClxBPAs were never detected, or quantified while for CKD5 and ESKDD patients one ClxBPAs at least has been detected or quantified in 14 patients (38.8%) and 24 patients (37.5%), respectively. Dialysis therapy was inefficient to remove BPA either for HD (1.983 ± 6.042 ng/mL in pre-dialysis versus 3.675 ± 8.445 ng/mL in post-dialysis) or HDF (2.434 ± 5.042 ng/mL in pre-dialysis versus 7.462 ± 15.960 ng/mL in post dialysis) regarding pre-post BPA concentrations (p > 0.05). The same result was observed regarding ClxBPA analysis. Presence of polysulfone in dialyzer fibers overexposed ESKDD patients to BPA in pre-dialysis samples with 3.054 ± 6.770 for ESKDD patients treated with a polysulfone dialyzer versus 0.708 ± 0.638 (p = 0.040) for ESKDD patients treated without a polysulfone dialyzer and to BPA in post-dialysis samples with 6.629 ± 13.932 for ESKDD patients treated with a polysulfone dialyzer versus 3.982 ± 11.004 (p = 0.018) for ESKDD patients treated without a polysulfone dialyzer. This work is to our knowledge the first to investigate, the impact of a dialysis session and materials used on BPA and ClxBPAs plasma concentrations and to compare these concentrations to those found in CKD5 patients and in healthy volunteers.

Cadmium and phthalate impacts developmental growth and mortality of Spodoptera littoralis, but not reproductive success.

Our environment is increasingly polluted with various molecules, some of which are considered endocrine disruptors. Metals and phthalates, originating from industrial activities, agricultural practices, or consumer products, are prominent examples of such pollutants. We experimentally investigated the impacts of the heavy metal cadmium and the phthalate DEHP on the moth Spodoptera littoralis. More specifically, larvae were reared in laboratory conditions, where they were exposed to diets contaminated with either two doses of cadmium at concentrations of 62.5 µg/g or 125 µg/g, two doses of DEHP at 100 ng/g and 10 µg/g, or a combination of both low and high doses of the two compounds, with a control group for comparison. Our findings indicate that cadmium delays the developmental transition from larva to adult. Notably, the combination of cadmium and DEHP exacerbated this delay, highlighting a synergistic effect. In contrast, DEHP alone did not affect larval development. Additionally, we observed that cadmium exposure, both alone and in combination with DEHP, led to a lower mass at all larval stages. However, cadmium-exposed individuals that reached adulthood eventually reached a similar mass to those in other groups. Interestingly, while our results did not show any effect of the treatments on hatching success, there was a higher adult mortality rate in the cadmium-treated groups. This suggests that while moths may prioritize reproductive success, their survival at the adult stage is compromised by cadmium exposure. In conclusion, our study demonstrates the impact of cadmium on the development, mass, and adult survival of moths, and reveals synergistic effects when combined with DEHP. These results confirm cadmium as an endocrine disruptor, even at low doses. These insights underscore the importance of understanding the toxicological effects of low doses of pollutants like cadmium and DEHP, both individually and in combination.

Female Mice Exposed to Pyriproxyfen Since Prepuberty Showed Reproductive Impairment During Sexual Maturity and Increased Fetal Death in Their Offspring.

Pyriproxyfen (PPF) is an insecticide used in agriculture, which is approved for use in drinking water tanks for human consumption. However, some studies indicate that it may act as an endocrine disruptor and affect nontarget organisms. This study aimed to evaluate the effects of PPF on reproduction and general health status in female mice exposed from pre-puberty to adulthood. In the first experiment, females were treated by gavage from postnatal day (PND) 23 to (PND) 75 and were distributed into three experimental groups: control (vehicle), PPF 0.1 mg/kg, and PPF 1 mg/kg. Female mice were assessed for the age of puberty onset, body mass, water and food consumption, and the estrous cycle. On PDN 75, a subgroup was euthanized, when vital and reproductive organs were collected and weighed. The thyroid, ovary, and uterus were evaluated for histomorphometry. The other subgroup was assessed in relation to reproductive performance and fetal parameters. In a second experiment, the uterotrophic assay was performed with juvenile females (PND 18) using doses of 0.01, 0.1, or 1 mg/kg of PPF. PPF treatment reduced thyroid mass and increased liver mass. Furthermore, there was an increase in ovarian interstitial tissue and, in the uterus, a decrease in the thickness of the endometrial stroma with reduced content of collagen fibers. There was also a reduction of 30% in pregnancy rate in the treated groups and an increase in the frequency of fetal death. This study suggests that, based on this experimental model, the insecticide may pose a reproductive risk for females chronically exposed to the substance from the pre-pubertal period until adulthood. These results raise concerns about prolonged exposure of women to the same compound.

Effects of Pharmaceutical Substances with Obesogenic Activity on Male Reproductive Health.

Obesogens have been identified as a significant factor associated with increasing obesity rates, particularly in developed countries. Substances with obesogenic traits are prevalent in consumer products, including certain pharmaceuticals. Specific classes of pharmaceuticals have been recognized for their ability to induce weight gain, often accompanied by hormonal alterations that can adversely impact male fertility. Indeed, research has supplied evidence underscoring the crucial role of obesogens and therapeutic agents in the normal functioning of the male reproductive system. Notably, sperm count and various semen parameters have been closely linked to a range of environmental and nutritional factors, including chemicals and pharmacological agents exhibiting obesogenic properties. This review aimed to explore studies focused on analyzing male fertility parameters, delving into the intricacies of sperm quality, and elucidating the direct and adverse effects that pharmacological agents may have on these aspects.

Integrative Bioinformatics-Gene Network Approach Reveals Linkage between Estrogenic Endocrine Disruptors and Vascular Remodeling in Peripheral Arterial Disease.

Vascular diseases, including peripheral arterial disease (PAD), pulmonary arterial hypertension, and atherosclerosis, significantly impact global health due to their intricate relationship with vascular remodeling. This process, characterized by structural alterations in resistance vessels, is a hallmark of heightened vascular resistance seen in these disorders. The influence of environmental estrogenic endocrine disruptors (EEDs) on the vasculature suggests a potential exacerbation of these alterations. Our study employs an integrative approach, combining data mining with bioinformatics, to unravel the interactions between EEDs and vascular remodeling genes in the context of PAD. We explore the molecular dynamics by which EED exposure may alter vascular function in PAD patients. The investigation highlights the profound effect of EEDs on pivotal genes such as ID3, LY6E, FOS, PTP4A1, NAMPT, GADD45A, PDGF-BB, and NFKB, all of which play significant roles in PAD pathophysiology. The insights gained from our study enhance the understanding of genomic alterations induced by EEDs in vascular remodeling processes. Such knowledge is invaluable for developing strategies to prevent and manage vascular diseases, potentially mitigating the impact of harmful environmental pollutants like EEDs on conditions such as PAD.

Liver and Pancreatic Toxicity of Endocrine-Disruptive Chemicals: Focus on Mitochondrial Dysfunction and Oxidative Stress.

In recent years, the worldwide epidemic of metabolic diseases, namely obesity, metabolic syndrome, diabetes and metabolic-associated fatty liver disease (MAFLD) has been strongly associated with constant exposure to endocrine-disruptive chemicals (EDCs), in particular, the ones able to disrupt various metabolic pathways. EDCs have a negative impact on several human tissues/systems, including metabolically active organs, such as the liver and pancreas. Among their deleterious effects, EDCs induce mitochondrial dysfunction and oxidative stress, which are also the major pathophysiological mechanisms underlying metabolic diseases. In this narrative review, we delve into the current literature on EDC toxicity effects on the liver and pancreatic tissues in terms of impaired mitochondrial function and redox homeostasis.

Extracellular Vesicles in Environmental Toxicological Studies: Association between Urinary Concentrations of Phthalate Metabolites and Exosomal miRNA Expression Profiles.

Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to phthalates and the level of circulating microRNAs (miRs), especially those miRs encapsulated in extracellular vesicles/exosomes or exosome-like vesicles (ELVs). We examined the relationship of ELV-miR expression patterns and urine of adult men with five phthalate metabolites (i.e., mono isobutyl phthalate, mono-n-butyl phthalate, mono benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethylhexyl) phthalate) to identify potential biomarkers and relevant pathways. We found significant positive associations which were further confirmed by multivariable analysis. Overall, our analyses showed that the Σ phthalate metabolite concentration was associated with a significant increase in the expression level of two miRs found in ELV: miR-202 and miR-543. Different pathways including cancer and immune-related responses were predicted to be involved in this relationship. Analyzing the specific downstream target genes of miR-202 and miR-543, we identified the phosphatase and tensin homolog (PTEN) as the key gene in several converging pathways. In summary, the obtained results demonstrate that exposure to environmental phthalates could be related to altered expression profiles of specific ELV-miRs in adult men, thereby demonstrating the potential of miRs carried by exosomes to act as early effect biomarkers.

The Role of Endocrine Disruptors Bisphenols and Phthalates in Obesity: Current Evidence, Perspectives and Controversies.

Excess body weight constitutes one of the major health challenges for societies and healthcare systems worldwide. Besides the type of diet, calorie intake and the lack of physical exercise, recent data have highlighted a possible association between endocrine-disrupting chemicals (EDCs), such as bisphenol A, phthalates and their analogs, and obesity. EDCs represent a heterogeneous group of chemicals that may influence the hormonal regulation of body mass and adipose tissue morphology. Based on the available data from mechanistic, animal and epidemiological studies including meta-analyses, the weight of evidence points towards the contribution of EDCs to the development of obesity, associated disorders and obesity-related adipose tissue dysfunction by (1) impacting adipogenesis; (2) modulating epigenetic pathways during development, enhancing susceptibility to obesity; (3) influencing neuroendocrine signals responsible for appetite and satiety; (4) promoting a proinflammatory milieu in adipose tissue and inducing a state of chronic subclinical inflammation; (5) dysregulating gut microbiome and immune homeostasis; and (6) inducing dysfunction in thermogenic adipose tissue. Critical periods of exposure to obesogenic EDCs are the prenatal, neonatal, pubertal and reproductive periods. Interestingly, EDCs even at low doses may promote epigenetic transgenerational inheritance of adult obesity in subsequent generations. The aim of this review is to summarize the available evidence on the role of obesogenic EDCs, specifically BPA and phthalate plasticizers, in the development of obesity, taking into account in vitro, animal and epidemiologic studies; discuss mechanisms linking EDCs to obesity; analyze the effects of EDCs on obesity in critical chronic periods of exposure; and present interesting perspectives, challenges and preventive measures in this research area.

Is Physical Activity an Efficient Strategy to Control the Adverse Effects of Persistent Organic Pollutants in the Context of Obesity? A Narrative Review.

Obesity affects nearly 660 million adults worldwide and is known for its many comorbidities. Although the phenomenon of obesity is not fully understood, science regularly reveals new determinants of this pathology. Among them, persistent organic pollutants (POPs) have been recently highlighted. Mainly lipophilic, POPs are normally stored in adipose tissue and can lead to adverse metabolic effects when released into the bloodstream. The main objective of this narrative review is to discuss the different pathways by which physical activity may counteract POPs' adverse effects. The research that we carried out seems to indicate that physical activity could positively influence several pathways negatively influenced by POPs, such as insulin resistance, inflammation, lipid accumulation, adipogenesis, and gut microbiota dysbiosis, that are associated with the development of obesity. This review also indicates how, through the controlled mobilization of POPs, physical activity could be a valuable approach to reduce the concentration of POPs in the bloodstream. These findings suggest that physical activity should be used to counteract the adverse effects of POPs. However, future studies should accurately assess its impact in specific situations such as bariatric surgery, where weight loss promotes POPs' blood release.

Estrogenic activity in wastewater treatment plants through in vitro effect-based assays: Insights into extraction phase.

Effluents of wastewater treatment plants can abundantly spread endocrine disrupting chemicals in the environment. To improve water quality monitoring, the use of effect-based tools that measure estrogenic activity has been suggested, however their results could be influenced by different factors. This study compared the estrogenic activity of wastewater samples extracted with two stationary phases and tested with two in vitro effect-based assays to investigate whether and how stationary phases and assays could influence biomonitoring data. During four seasonal periods, the effluents of six WWTPs located in northern Italy were sampled. After the extraction using two different stationary phases (HLB, C18), the samples (n = 72) were tested using two effect-based assays: a gene reporter luciferase assay on mammalian cells (MELN) and yeast estrogen screen assay (YES). The results showed that estrogenic activity of HLB extracts was significantly different from the activity of C18 extracts, suggesting that extraction phase can influence biomonitoring data. Moreover, the estrogenic activity was overall higher using gene reporter MELN assay than using YES assay, suggesting that, due to difference in cell membrane permeability and metabolic activation, the applied cell model can affect the biomonitoring results. Finally, from the comparison between the activity of the final effluent and the environmentally safe estrogenic levels in surface waters, MELN data suggested that the activity of this effluent may pose an environmental risk, while YES data showed that it should not be considered a threat to the receiving surface waters. This study pointed out that a standardized approach is needed to assess the estrogenic activity of waters; it reported important data to select the most suitable stationary phase for samples extraction (samples extracted with C18 sorbent showed higher estradiol equivalent concentration values) and the most appropriate bioassay (gene reporter luciferase MELN assay was more sensitive than YES assay) to assess the environmental risk, thus protecting human health.

Laccase immobilization and its degradation of emerging pollutants: A comprehensive review.

The chronic lack of effective disposal of pollutants has resulted in the detection of a wide variety of EPs in the environment, with concentrations high enough to affect ecological health. Laccase, as a versatile oxidase capable of catalyzing a wide range of substrates and without producing toxic by-products, is a potential candidate for the biodegradation of pollutants. Immobilization can provide favorable protection for free laccase, improve the stability of laccase in complex environments, and greatly enhance the reusability of laccase, which is significant in reducing the cost of industrial applications. This study introduces the properties of laccase and subsequently elaborate on the different support materials for laccase immobilization. The research advances in the degradation of EDs, PPCPs, and PAHs by immobilized laccase are then reviewed. This review provides a comprehensive understanding of laccase immobilization, as well as the advantages of various support materials, facilitating the development of more economical and efficient immobilization systems that can be put into practice to achieve the green degradation of EPs.