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Purpose of reviewDepression during the perinatal or antenatal period affects at least 1 in 10 women worldwide, with long term health implications for the mother and child. Concurrently, there is increasing evidence associating maternal exposure to per- and poly-fluoroalkyl substances (PFAS) to adverse pregnancy outcomes. We reviewed the body of evidence examining both the associations between PFAS exposure and perturbations in the maternal metabolome, and the associations between the maternal metabolome and perinatal/antenatal depression. Through this, we sought to explore existing evidence of the perinatal metabolome as a potential mediation pathway linking PFAS exposure and perinatal/antenatal depression.Recent findingsThere are few studies examining the metabolomics of PFAS exposure-specifically in pregnant women-and the metabolomics of perinatal/antenatal depression, let alone studies examining both simultaneously. Of the studies reviewed (N = 11), the majority were cross sectional, based outside of the US, and conducted on largely homogenous populations. Our review identified 23 metabolic pathways in the perinatal metabolome common to both PFAS exposure and perinatal/antenatal depression. Future studies may consider findings from our review to conduct literature-derived hypothesis testing focusing on fatty acid metabolism, alanine metabolism, glutamate metabolism, and tyrosine metabolism when exploring the biochemical mechanisms conferring the risk of perinatal/antenatal depression due to PFAS exposure. We recommend that researchers also utilize heterogenous populations, longitudinal study designs, and mediation approaches to elucidate key pathways linking PFAS exposures to perinatal/antenatal depression.

BACKGROUND: Interventions are needed to help people reduce exposure to harmful chemicals from everyday products and lifestyle habits. Report-back of individual exposures is a potential pathway to increasing environmental health literacy (EHL) and readiness to reduce exposures. OBJECTIVES: Our objective was to determine if report-back of endocrine-disrupting chemicals (EDCs) can reduce EDC exposure, increase EHL, and increase readiness to change (i.e., to implement EDC exposure-reduction behaviors). METHODS: Participants in the Healthy Nevada Project completed EHL and readiness-to-change surveys before (n = 424) and after (n = 174) a report-back intervention. Participants used mail-in kits to measure urinary biomarkers of EDCs. The report-back of results included urinary levels, information about health effects, sources of exposure, and personalized recommendations to reduce exposure. RESULTS: EHL was generally very high at baseline, especially for questions related to the general pollution. For questions related to chemical exposures, responses varied across several demographics. Statistically reliable improvements in EHL responses were seen after report-back. For readiness to change, 72% were already or planning to change their behaviors. Post-intervention, women increased their readiness (p = 0.053), while men decreased (p = 0.007). When asked what challenges they faced in reducing exposure, 79% cited not knowing what to do. This dropped to 35% after report-back. Participants with higher propylparaben were younger (p = 0.03) and women and participants who rated themselves in better health had higher levels of some phthalates (p = 0.02-0.003 and p = 0.001-0.003, respectively). After report-back, monobutyl phthalate decreased among the 48 participants who had valid urine tests before and after the intervention (p < 0.001). CONCLUSIONS: The report-back intervention was successful as evidenced by increased EHL behaviors, increased readiness to change among women, and a decrease in monobutyl phthalate. An EHL questionnaire more sensitive to chemical exposures would help differentiate high and low literacy. Future research will focus on understanding why men decreased their readiness to change and how the intervention can be improved for all participants.

Developmental exposures to PCBs are implicated in the etiology of neurodevelopmental disorders (NDDs). This observation is concerning given the continued presence of PCBs in the human environment and the increasing incidence of NDDs. Previous studies reported that developmental exposure to legacy commercial PCB mixtures (Aroclors) or single PCB congeners found in Aroclors caused NDD-relevant behavioral phenotypes in animal models. However, the PCB congener profile in contemporary human samples is dissimilar to that of the legacy Aroclors, raising the question of whether human-relevant PCB mixtures similarly interfere with normal brain development. To address this question, we assessed the developmental neurotoxicity of the Fox River Mixture (FRM), which was designed to mimic the congener profile identified in fish from the PCB-contaminated Fox River that constitute a primary protein source in the diet of surrounding communities. Adult female C57BL/6 J mouse dams (8-10 weeks old) were exposed to vehicle (peanut oil) or FRM at 0.1, 1.0, or 6.0 mg/kg/d in their diet throughout gestation and lactation, and neurodevelopmental outcomes were assessed in their pups. Ultrasonic vocalizations (USVs) and measures of general development were quantified at postnatal day (P) 7, while performance in the spontaneous alternation task and the 3-chambered social approach/social novelty task was assessed on P35. Triiodothyronine (T3) and thyroxine (T4) were quantified in serum collected from the dams when pups were weaned and from pups on P28 and P35. Developmental exposure to FRM did not alter pup weight or body temperature on P7, but USVs were significantly decreased in litters exposed to FRM at 0.1 or 6.0 mg/kg/d in the maternal diet. FRM also impaired male and female pups' performance in the social novelty task. Compared to sex-matched vehicles, significantly decreased social novelty was observed in male and female pups in the 0.1 and 6.0 mg/kg/d dose groups. FRM did not alter performance in the spontaneous alternation or social approach tasks. FRM increased serum T3 levels but decreased serum T4 levels in P28 male pups in the 1.0 and 6.0 mg/kg/d dose groups. In P35 female pups and dams, serum T3 levels decreased in the 6.0 mg/kg/d dose group while T4 levels were not altered. Collectively, these findings suggest that FRM interferes with the development of social communication and social novelty, but not memory, supporting the hypothesis that contemporary PCB exposures pose a risk to the developing brain. FRM had sex, age, and dose-dependent effects on serum thyroid hormone levels that overlapped but did not perfectly align with the FRM effects on behavioral outcomes. These observations suggest that changes in thyroid hormone levels are not likely the major factor underlying the behavioral deficits observed in FRM-exposed animals.

Contaminated drinking water from widespread environmental pollutants such as perfluoroalkyl and polyfluoroalkyl substances (PFAS) poses a rising threat to public health. PFAS monitoring in groundwater is limited and fails to consider pesticides found to contain PFAS as a potential contamination source. Given previous findings on the disproportionate exposure of communities of Color to both pesticides and PFAS, we investigated disparities in PFAS-contaminated pesticide applications in California based on community-level sociodemographic characteristics. We utilized statewide pesticide application data from the California Department of Pesticide Regulation and recently reported concentrations of PFAS chemicals detected in eight pesticide products to calculate the areal density of PFAS applied within 1 km of individual community water systems' (CWSs) supply wells. Spatial regression analyses suggest that statewide, CWSs that serve a greater proportion of Latinx and non-Latinx People of Color residents experience a greater areal density of PFAS applied and greater likelihood of PFAS application near their public supply wells. These results highlight agroecosystems as potentially important sources of PFAS in drinking water and identify areas that may be at risk of PFAS contamination and warrant additional PFAS monitoring and remediation.

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Background Neurodevelopmental disorders have a strong male bias that is poorly understood. Placenta is a rich source of molecular information about environmental interactions with genetics (including biological sex), that affect the developing brain. We investigated placental-brain transcriptional responses in an established mouse model of prenatal exposure to a human-relevant mixture of polychlorinated biphenyls (PCBs). Results To understand sex, tissue, and dosage effects in embryonic (E18) brain and placenta by RNAseq, we used weighted gene correlation network analysis (WGCNA) to create correlated gene networks that could be compared across sex or tissue. WGCNA revealed that expression within most correlated gene networks was significantly and strongly associated with PCB exposures, but frequently in opposite directions between male-female and placenta-brain comparisons. In both WGCNA and differentially expressed gene analyses, male brain showed more PCB-induced transcriptional changes than male placenta, but the reverse pattern was seen in females. Furthermore, non-monotonic dose responses to PCBs were observed in most gene networks but were most prominent in male brain. The transcriptomic effects of low dose PCB exposure were significantly reversed by dietary folic acid supplementation across both sexes, but these effects were strongest in female placenta. PCB-dysregulated and folic acid-reversed gene networks were commonly enriched in functions in metabolic pathways involved in energy usage and translation, with female-specific protective effects enriched in PPAR, thermogenesis, glycerolipids, and O-glycan biosynthesis, as opposed to toxicant responses in male brain. Conclusions The female protective effect in prenatal PCB exposures appears to be mediated by dose-dependent sex differences in transcriptional modulation of metabolism in placenta. Graphical Abstract

Cardiometabolic disorders (CMD) are a growing public health problem across the world. Among the known cardiometabolic risk factors are compounds that induce endocrine and metabolic dysfunctions, such as endocrine disrupting chemicals (EDCs). To date, how EDCs influence molecular programs and cardiometabolic risks has yet to be fully elucidated, especially considering the complexity contributed by species-, chemical-, and dose-specific effects. Moreover, different experimental and analytical methodologies employed by different studies pose challenges when comparing findings across studies. To explore the molecular mechanisms of EDCs in a systematic manner, we established a data-driven computational approach to meta-analyze 30 human, mouse, and rat liver transcriptomic datasets for 4 EDCs, namely bisphenol A (BPA), bis(2-ethylhexyl) phthalate (DEHP), tributyltin (TBT), and perfluorooctanoic acid (PFOA). Our computational pipeline uniformly re-analyzed pre-processed quality-controlled microarray data and raw RNAseq data, derived differentially expressed genes (DEGs) and biological pathways, modeled gene regulatory networks and regulators, and determined CMD associations based on gene overlap analysis. Our approach revealed that DEHP and PFOA shared stable transcriptomic signatures that are enriched for genes associated with CMDs, suggesting similar mechanisms of action such as perturbations of peroxisome proliferator-activated receptor gamma (PPARγ) signaling and liver gene network regulators VNN1 and ACOT2. In contrast, TBT exhibited highly divergent gene signatures, pathways, network regulators, and disease associations from the other EDCs. In addition, we found that the rat, mouse, and human BPA studies showed highly variable transcriptomic patterns, providing molecular support for the variability in BPA responses. Our work offers insights into the commonality and differences in the molecular mechanisms of various EDCs and establishes a streamlined data-driven workflow to compare molecular mechanisms of environmental substances to elucidate the underlying connections between chemical exposure and disease risks.

BackgroundOrganophosphorus pesticides (OP) have been associated with various human health conditions. Animal experiments and in-vitro models suggested that OP may also affect the gut microbiota. We examined associations between ambient chronic exposure to OP and gut microbial changes in humans.MethodsWe recruited 190 participants from a community-based epidemiologic study of Parkinson's disease living in a region known for heavy agricultural pesticide use in California. Of these, 61% of participants had Parkinson's disease and their mean age was 72 years. Microbiome and predicted metagenome data were generated by 16S rRNA gene sequencing of fecal samples. Ambient long-term OP exposures were assessed using pesticide application records combined with residential addresses in a geographic information system. We examined gut microbiome differences due to OP exposures, specifically differences in microbial diversity based on the Shannon index and Bray-Curtis dissimilarities, and differential taxa abundance and predicted Metacyc pathway expression relying on regression models and adjusting for potential confounders.ResultsOP exposure was not associated with alpha or beta diversity of the gut microbiome. However, the predicted metagenome was sparser and less evenly expressed among those highly exposed to OP (p = 0.04). Additionally, we found that the abundance of two bacterial families, 22 genera, and the predicted expression of 34 Metacyc pathways were associated with long-term OP exposure. These pathways included perturbed processes related to cellular respiration, increased biosynthesis and degradation of compounds related to bacterial wall structure, increased biosynthesis of RNA/DNA precursors, and decreased synthesis of Vitamin B1 and B6.ConclusionIn support of previous animal studies and in-vitro findings, our results suggest that ambient chronic OP pesticide exposure alters gut microbiome composition and its predicted metabolism in humans.

BACKGROUND: Consuming ultra-processed foods may increase exposure to phthalates, a group of endocrine disruptors prevalent in food contact materials. OBJECTIVES: Investigate associations between ultra-processed food intake and urinary phthalates during pregnancy, and evaluate whether ultra-processed foods mediate socioeconomic disparities in phthalate exposures. METHODS: In a socioeconomically diverse sample of 1031 pregnant women from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study in the urban South, the Block Food Frequency Questionnaire was administered and urinary phthalate metabolites were measured in the second trimester. Linear regressions modeled associations between phthalates and overall ultra-processed food consumption, individual ultra-processed foods, and exploratory factor analysis dietary patterns. Causal mediation analyses examined whether ultra-processed food intake mediates relationships between socioeconomic disparities and phthalate exposures. RESULTS: Ultra-processed foods constituted 9.8-59.0 % (mean = 38.6 %) of participants diets. 10 % higher dietary proportion of ultra-processed foods was associated with 13.1 % (95 %CI: 3.4 %-22.9 %) higher molar sum concentrations of di(2-ethylhexyl) phthalate metabolites (ΣDEHP). 10 % higher consumption of minimally-processed foods was associated with lower ΣDEHP (10.8 %: 3.4 %-22.9 %). Ultra- and minimally-processed food consumption were not associated with non-DEHP metabolites. Standard deviation higher consumptions of hamburger/cheeseburger, French fries, soda, and cake were associated with 10.5 % (4.2 %-17.1 %), 9.2 % (2.6 %-16.2 %), 7.4 % (1.4 %-13.6 %), and 6.0 % (0.0 %-12.4 %), respectively, higher ΣDEHP. Exploratory factor analysis corroborated positive associations of processed food with ΣDEHP, and uncovered a healthy dietary pattern associated with lower urinary ΣDEHP, mono(2-ethyl-5-hydroxyhexyl) (MEHHP), mono(2-ethyl-5-carboxypentyl) (MECPP), mono(2-carboxymethylhexyl) (MCMHP), and mono-isononyl (MINP) phthalates. Significant indirect effects indicated that lower income and education levels were associated with 1.9 % (0.2 %-4.2 %) and 1.4 % (0.1 %-3.3 %) higher ΣDEHP, respectively, mediated via increased ultra-processed food consumption. CONCLUSIONS: Consumption of ultra-processed foods may increase exposure to phthalates. Policies to reduce dietary phthalate exposures from food packaging and processing are needed, as socioeconomic barriers can preclude dietary recommendations as a sole means to reduce phthalate exposures.

BackgroundWidespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results.ObjectivesWe conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex.MethodsWe included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as log2-transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex.ResultsThree OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in >85% of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling=1.07; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect=1.25; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age z-scores (β for detect vs. nondetect=0.04-0.07); other chemicals showed null associations.DiscussionIn the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.

Cornified envelopes (CEs) of human epidermis ordinarily consist of transglutaminase-mediated cross-linked proteins and are essential for skin barrier function. However, in addition to enzyme-mediated isopeptide bonding, protein cross-linking could also arise from oxidative damage. Our group recently demonstrated abnormal incorporation of cellular proteins into CEs by pro-oxidants in woodsmoke. In this study, we focused on 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), mesquite liquid smoke (MLS), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to further understand the mechanisms through which environmental pro-oxidants induce CE formation and alter the CE proteome. CEs induced by the ionophore X537A were used for comparison. Similar to X537A, DMNQ- and MLS-induced CE formation was associated with membrane permeabilization. However, since DMNQ is non-adduct forming, its CEs were similar in protein profile to those from X537A. By contrast, MLS, rich in reactive carbonyls that can form protein adducts, caused a dramatic change in the CE proteome. TCDD-CEs were found to contain many CE precursors, such as small proline-rich proteins and late cornified envelope proteins, encoded by the epidermal differentiation complex. Since expression of these proteins is mediated by the aryl hydrocarbon receptor (AhR), and its well-known downstream protein, CYP1A1, was exclusively present in the TCDD group, we suggest that TCDD alters the CE proteome through persistent AhR activation. This study demonstrates the potential of environmental pro-oxidants to alter the epidermal CE proteome and indicates that the cellular redox state has an important role in CE formation.

AbstractBisphenol A (BPA), a known endocrine disruptor, is commonly used in food containers and packaging. Recently, alternatives such as bisphenol AF (BPAF), bisphenol B (BPB), and bisphenol E (BPE) have been introduced to replace BPA. However, these substitutes have been reported to exhibit toxicity levels similar to BPA. In this study, we developed and validated a method for the analysis of trace bisphenols (BPA, BPAF, BPB, and BPE) in food using immunoaffinity column (IAC) clean-up. The method demonstrated satisfactory accuracy and precision. We applied this validated method to analyze 56 carbonated beverage samples and 30 canned tuna samples. In the carbonated beverages, average concentrations of BPA and BPAF were 0.4 and 0.2 μg kg−1, respectively. In canned tuna, BPA and BPAF were found at average concentrations of 22.2 and 0.7 μg kg−1, respectively, while BPB and BPE were not detected in any samples. Estimated exposure levels ranged from 0.13 to 0.18 ng kg bw−1 day−1 in the general population and from 205.2 to 232.0 ng kg bw−1 day−1 among consumers. The commercial IAC-based analytical method used in this study can contribute to the safety management of BPA, BPAF, BPB, and BPE. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to endocrine disrupting chemicals (EDCs) can result in alterations of natural hormones in the body. The aim of this review article is to highlight the knowledge about EDCs and obesity. Methods: A scoping review of the electronic literature was performed using PubMed platform for studies on EDCs and obesity published between the years 2013–2023. A total of 10 systematic reviews and meta-analysis studies met our inclusion criteria on more prominent EDCs focusing mainly on bisphenols, including parabens, triclosan, and phthalates, and their association with obesity. Design: Scoping review. Results: EDCs, mostly bisphenols and phthalates, are related to health effects, while there is less information on the impact of parabens and triclosan. A series of negative physiological effects involving obesogenic, diabetogenic, carcinogenic, and inflammatory mechanisms as well as epigenetic and microbiota modulations was related to a prolonged EDCs exposure. A more profound research of particular pollutants is required to illuminate the accelerating effects of particular EDCs, mixtures or their metabolites on the mechanism of the development of obesity. Conclusion: Considering the characteristics of EDCs and the heterogeneity of studies, it is necessary to design specific studies of effect tracking and, in particular, education about daily preventive exposure to EDCs for the preservation of long-term public health. [ABSTRACT FROM AUTHOR]

AbstractEmerging endocrine-disrupting chemicals (EDCs) are a diverse group of toxic substances that disrupt the endocrine system. These substances can only be approved after obtaining concrete evidence of their toxicity. New approach methodologies (NAMs) offer information tailored to the intended application while reducing the use of animals. NAMs aim to develop quantitative structure-activity relationship (QSAR) and quantitive-Read-Across structure-activity relationship (q-RASAR) models to predict and categorize the acute toxicity of known and unknown EDCs. The q-RASAR model was constructed and verified using validation metrics (R2 = 0.886 and Q2 = 0.814). The substructure fingerprint was well-fitted for the classification model and the model was validated using 10-fold average accuracy (Q = 86.88%), specificity (Sp = 88.89%), Matthew’s correlation curve (MCC = 0.621) and receiver operating characteristics (ROC = 0.828). The dataset of unknown substances revealed that phenolphthalein (Php) exhibited a significant level of toxicity. The docking and simulation study results indicated that the computationally derived important features successfully bound to the target zebrafish sex hormone binding globulin (zfSHBG). The experimental LC50 value of 0.790 mg L−1 was very close to the predicted value of 0.763 mg L−1, which provides high confidence to the developed model. [ABSTRACT FROM AUTHOR]

Maternal exposure to endocrine-disrupting chemicals (EDCs) in human pregnancy is widely considered as an important cause of adverse changes in male reproductive health due to impaired foetal androgen production/action. However, the epidemiological evidence supporting this view is equivocal, except for certain phthalates, notably diethyl hexyl phthalate (DEHP). Maternal phthalate exposure levels associated with adverse reproductive changes in epidemiological studies are several thousand-fold lower than those needed to suppress foetal androgen production in rats, and direct studies using human foetal testis tissue show no effect of high phthalate exposure on androgen production. This conundrum is unexplained and raises fundamental questions. Human DEHP exposure is predominantly via food with highest exposure associated with consumption of a Western style (unhealthy) diet. This diet is also associated with increased exposure to the most common EDCs, whether persistent (chlorinated or fluorinated chemicals) or non-persistent (phthalates, bisphenols) compounds, which are found at highest levels in fatty and processed foods. Consequently, epidemiological studies associating EDC exposure and male reproductive health disorders are confounded by potential dietary effects, and vice versa. A Western diet/lifestyle in young adulthood is also associated with low sperm counts. Disentangling EDC and dietary effects in epidemiological studies is challenging. In pregnancy, a Western diet, EDC exposure, and maternal living in proximity to industrial sites are all associated with impaired foetal growth/development due to placental dysfunction, which predisposes to congenital male reproductive disorders (cryptorchidism, hypospadias). While the latter are considered to reflect impaired foetal androgen production, effects resulting from foetal growth impairment (FGI) are likely indirect. As FGI has numerous life-long health consequences, and is affected by maternal lifestyle, research into the origins of male reproductive disorders should take more account of this. Additionally, potential effects on foetal growth/foetal testis from the increasing use of medications in pregnancy deserves more research attention. [ABSTRACT FROM AUTHOR]

• The DEHP was detected in serum and hair of M. berezovskii in captivity in some farms. • MA fed female M. berezovskii improved the survival rate of M. berezovskii pups. • DEHP induces oxidative stress and apoptosis of PMCs by reducing PRDX6 expression. • MA prevents DEHP inducing apoptosis via upregulating PRDX6 in PMCs. Chinese forest musk deer (FMD), an endangered species, have exhibited low reproductive rates even in captivity due to stress conditions. Investigation revealed the presence of di(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, in the serum and skin of captive FMDs. Feeding FMDs with maslinic acid (MA) has been observed to alleviate the stress response and improve reproductive rates, although the precise molecular mechanisms remain unclear. Therefore, this study aims to investigate the molecular mechanisms underlying the alleviation of DEHP-induced oxidative stress and cell apoptosis in primary peritubular myoid cells (PMCs) through MA intake. Primary PMCs were isolated and exposed to DEHP in vitro. The results demonstrated that DEHP significantly suppressed antioxidant levels and promoted cell apoptosis in primary PMCs. Moreover, interfering with the expression of PRDX6 was found to induce excessive reactive oxygen species (ROS) production and cell apoptosis in primary PMCs. Supplementation with MA significantly upregulated the expression of PRDX6, thereby attenuating DEHP-induced oxidative stress and cell apoptosis in primary PMCs. These findings provide a theoretical foundation for mitigating stress levels and enhancing reproductive capacity of in captive FMDs. [Display omitted] [ABSTRACT FROM AUTHOR]

Early brain development depends on adequate transport of thyroid hormones (THs) from the maternal circulation to the fetus. To reach the fetal brain, THs have to cross several physiological barriers, including the placenta, blood–brain-barrier and blood–cerebrospinal fluid-barrier. Transport across these barriers is facilitated by thyroid hormone transmembrane transporters (THTMTs). Some endocrine disrupting chemicals (EDCs) can interfere with the transport of THs by THTMTs. To screen chemicals for their capacity to disrupt THTMT facilitated TH transport, in vitro screening assays are required. In this study, we developed assays for two THTMTs, organic anion transporter polypeptide 1C1 (OATP1C1) and organic anion transporter 4 (OAT4), both known to play a role in the transport of THs across barriers. We used overexpressing cell models for both OATP1C1 and OAT4, which showed an increased uptake of radiolabeled T4 compared to control cell lines. Using these models, we screened various reference and environmental chemicals for their ability to inhibit T4 uptake by OATP1C1 and OAT4. Tetrabromobisphenol A (TBBPA) was identified as an OATP1C1 inhibitor, more potent than any of the reference chemicals tested. Additionally perfluorooctanesulfonic acid (PFOS), perfluoroctanic acid (PFOA), pentachlorophenol and quercetin were identified as OATP1C1 inhibitors in a similar range of potency to the reference chemicals tested. Bromosulfophthalein, TBBPA, PFOA and PFOS were identified as potent OAT4 inhibitors. These results demonstrate that EDCs commonly found in our environment can disrupt TH transport by THTMTs, and contribute to the identification of molecular mechanisms underlying TH system disruption chemicals. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound. Its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after exposure to BPA (10 mg/L via drinking water for 90 days). Four groups were taken in this study – Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress, and antioxidants were also determined. HFD + BPA group rats showed a significant decline in memory function in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule-associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor– kappa B (NF-КB) in the brain. Obesity also caused significant (p < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (p < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases. [ABSTRACT FROM AUTHOR]

Globally, there is a move towards using local, native species for ecotoxicological risk assessments. Anthropogenic stressors from urban, agricultural, and industrial activities can impact the health of receiving ecosystems. Biomarkers can provide valuable insights as early warning signals of the potential environmental impacts of stressors. The aim of this study was to develop biomarkers in the green-lipped mussel (Perna canaliculus), a potential bioindicator of environmental health for coastal marine ecosystems in New Zealand. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays targeting the expression of genes involved in oxidative stress, xenobiotic transfer, membrane transportation, cellular and DNA response/repair, and endocrine disruption were developed and validated for P. canaliculus. We found significant modulation of genes associated with oxidative stress, xenobiotic transfer, membrane transport, endocrine disruption, and genotoxicity in P. canaliculus following 48-hour exposures to copper and benzo[α]pyrene. These results demonstrate the potential of P. canaliculus as a bioindicator species for environmental risk assessment. The gene expression assays showed potential as early indicators of exposure to the chemicals tested but require additional validation to assess their ability to predict effects at higher levels of biological organisation. [ABSTRACT FROM AUTHOR]

This editorial from the NORA: Nordic Journal of Women's Studies discusses the presence and significance of sex hormones in the Nordic region. It explores how sex hormones are used to regulate, optimize, and disrupt gendered bodies, and how their value and emotional impact vary across different contexts. The editorial also highlights the role of the Nordic welfare states in regulating hormonal distribution and disciplining hormonal bodies. The special issue aims to contribute to the feminist interdisciplinary dialogue on sex hormones and their impact on gender, age, race, ethnicity, health, and sexuality. The issue includes articles on topics such as hormonal and genetic testing, news stories about transgender and intersex athletes, the hormonalization of sports, and the cultural logics of testosterone in men's health. The editorial concludes by expressing gratitude to the contributing authors, reviewers, and the journal team. [Extracted from the article]

Hormones are molecular messengers in the body's metabolism. They regulate, for instance, reproduction, digestion, organ systems and gene expression. The past century brought with it a proliferation of synthetic substances and other industrial chemical compounds, generally referred to as endocrine-disrupting chemicals (EDCs). These chemicals interfere with the hormonal systems of human and animal bodies alike and are able to, among other things, fundamentally disrupt, mimic or block the functioning of the hormonal system. In this article I investigate the forces of chemical toxicity and its impact on all living bodies on this planet from a queer and trans perspective. EDCs and specifically EDC discourses have a particular effect on queer- and transness. Applying queer reading and autoethnography, I want to think here with two performances by Finnish artist Teo Ala-Ruona about the impact of EDCs on our human bodies, our planet and the relations and imaginaries that emerge in Ala-Ruona's work, blending transness and endocrine disruptors in ways different to those currently being suggested by life science and populist discourses. In my engagement with Ala-Ruona's work I consider that his work not only materializes a new imaginary of embodiment but also demonstrates a multi-molecular, rebellious becoming with and through toxins that intervenes in the risk narratives commonly flanking EDC discourses. [ABSTRACT FROM AUTHOR]

This review examined the global issue of endocrine disrupting compounds (EDCs) in drinking water, including their sources, health effects, and the efficacy of advanced treatment technologies like biodegradation and photocatalytic degradation, using case studies. Recently, endocrine disrupting substances or disruptors in drinking water have become a global issue. Emerging pollutants including endocrine disrupting chemicals can enter the body through water drinking. Endocrine disruptors affect gene expression and damage the endocrine system, harming humans, wildlife, and the environment. Pesticides, detergents and surfactants, plasticizers, industrial compounds, medicines, natural plant derivatives, and heavy metals are endocrine disruptive compounds in water. These endocrine disrupting substances enter raw water bodies by untreated and treated wastewater discharges, runoff, and leachate. However, the convectional drinking water treatment facility cannot cleanse and process endocrine disruptive substances from raw water intakes, resulting in inefficient eliminations and health risks. Mechanisms, benefits, and drawbacks of new water treatment technologies such biodegradation, photocatalytic degradation, and oxidation for endocrine disruptive chemicals are reviewed. Thus, many case studies from the Philippines, Mexico, and Egypt will be examined to highlight the health dangers of EDC exposure. [ABSTRACT FROM AUTHOR]

The levels of three phenolic endocrine-disrupting compounds (EDCs), NP, BPA and 4-t-OP were determined in water and sediment collected from sites along the Xiangjiang River, Zunyi, China. The NP, BPA and 4-t-OP concentrations ranged from 18.02 to 311.79 ng/L in the surface water, 16.04–408.12 ng/L in the submerged water, and 21.13–892.37 μg/kg dw in the sediment. NP contamination was most severe in both the river water and sediment. The ranges of the three phenolic EDCs were slightly greater in the submerged water than in the surface water (p > 0.05). The concentrations in the middle reaches were greater than those in the upstream and downstream reaches in both the water and sediment, and significant differences in content were detected in some reaches. The levels of three phenolic EDCs in the water and sediment had a positive correlation. In addition, the distribution coefficient (Kd) indicated that NP was more likely to adsorb to the sediment, and BPA and 4-t-OP were more likely to adsorb to river water. Moreover, the risk quotient (RQ) and hazard quotients (HQ) were used to reveal the environmental and health risks caused by coexposure to the three phenolic pollutants. The results showed that the current pollution is a threat to the environment of the study area and not a threat to the health of the local population. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting compounds (EDCs) are ubiquitous in soil, posing serious risks to soil biota, especially earthworms, which have been found to be affected by these compounds, despite not being their typical target organisms. Earthworms are essential for sustaining soil health and quality, by promoting soil aeration, organic matter decomposition and nutrient cycling, among other functions. This review synthesizes available literature evidencing the negative impact of EDC exposure, through traditional endocrine pathways and other toxicological mechanisms, on histopathological, biochemical, molecular and reproductive endpoints of earthworms. The compounds described, in the consulted literature, to induce histopathological, biochemical, genotoxicity and molecular and reproductive alterations include antibiotics, antimicrobial additives, flame retardants, fragrances, fungicides, herbicides, hormones, inorganic ions, insecticides, organic UV filters, parabens, perfluoroalkyl substances, pesticides, petroleum derivatives, plasticizers and polychlorinated biphenyls. These compounds reach soil through direct application or via contaminated organic amendments and water derived from potentially polluted sources. The findings gather in the present review highlight the vulnerability of earthworms to a broad spectrum of chemicals with endocrine disrupting capacity. Additionally, these studies emphasize the physiological disruptions caused by EDC exposure, underscoring the critical need to protect biodiversity, including earthworms, to ensure soil quality and ecosystem sustainability. Ongoing research has provided insights into molecular mechanisms responsive to EDCs in earthworms, including the identification of putative hormone receptors that exhibit functional similarity to those present in vertebrates. In conclusion, this review emphasizes the impact of EDCs in earthworms, especially through non-hormonal mediated pathways, and addresses the need for strong regulatory frameworks to mitigate the detrimental effects of EDCs on soil invertebrates in order to safeguard soil ecosystems. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a heavy metal that acts as endocrine disrupting chemical (EDC). Few studies have investigated the effects of Cd exposure on metabolic dysfunctions, such as type 1 and 2 diabetes mellitus (T1DM and T2DM). Thus, we assessed whether subacute Cd exposure at occupational levels causes abnormalities in white adipose tissue (WAT), liver, pancreas, and skeletal muscle. We administered cadmium chloride (CdCl2) (100 ppm in drinking water for 30 days) to female rats and evaluated Cd levels in serum and metabolic organs, morphophysiology, inflammation, oxidative stress, fibrosis, and gene expression. High Cd levels were found in serum, WAT, liver, pancreas, and skeletal muscle. Cd‐exposed rats showed low adiposity, dyslipidemia, insulin resistance, systemic inflammation, and oxidative stress compared to controls. Cd exposure reduced adipocyte size, hyperleptinemia, increased cholesterol levels, inflammation, apoptosis and fibrosis in WAT. Cd‐exposed rats had increased liver cholesterol levels, insulin receptor beta (IRβ) and peroxisome proliferator‐activated receptor‐gamma coactivator‐1alpha (PGC1α) expression, karyomegaly, inflammation, and fibrosis. Cd exposure reduced insulin levels and pancreatic islet size and increased inflammation and fibrosis. Cd exposure reduced skeletal muscle fiber diameter and increased IR expression and inflammation. Finally, strong positive correlations were observed between serum, tissue Cd levels, abnormal morphology, tissue inflammation and fibrosis. Thus, these data suggest that subacute Cd exposure impairs WAT, liver, pancreas and skeletal muscle function, leading to T1DM and T2DM features and other complications in female rats. [ABSTRACT FROM AUTHOR]

Background/ Objectives: Rosacea is a common chronic inflammatory skin disorder. Endocrinedisrupting chemicals (EDC) are toxic substances, that may gain entry through the skin and subsequently interfere with hormonal and immune functions. Bisphenol A (BPA) and pentachlorophenol sodium (PCS) are two of these EDCs, incriminated in the pathogenesis of certain inflammatory skin disorders. We aimed to test the hypothesis that exposure to BPA and PCS might be involved in the pathogenesis of rosacea. Methods: This prospective cross-sectional study involved 34 patients with rosacea (18F/16 M; mean age 48.5 ± 11 years) and 34 age and sex-matched healthy controls (20 F/14 M; mean age 48.2 ± 10.2 years). Main anthropometric measures, fasting plasma glucose (FPG), insulin, HOMA-IR, lipids, C-reactive protein (CRP), BPA, and PCS levels were quantified and recorded. Results: Serum CRP (9.6 ± 3.4 vs. 3.7 ± 1.6 mg/L, respectively, p0.05 for all). Serum BPA levels were 55.8 ± 14.4 and 51.9 ± 19.2 ng/mL, and PCS levels were 63.3 ± 45.9 ng/mL and 68.6 ± 40.8 ng/mL for patients and healthy controls, respectively. There was no significant difference in BPA and PCS levels between the two groups (p > 0.05 for both). No significant association was found among HOMAIR, CRP, BPA, and PCS levels (p > 0.05 for all). Conclusions: Although the present study fails to provide presumptive evidence for the role of BPA and PCS in rosacea, the question as to other EDCs might be involved in its etiopathogenesis remains. This hypothesis requires confirmation in large-scale future prospective trials. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a chemical substance used in the plastic industry and considered as an endocrine disruptor. Ginger is a herbal material used in the food industry and has antioxidant activity. The present study was performed to evaluate the histological changes in the thyroid gland of adult male albino rats after intake of BPA and if there is any protective role for ginger extract (GE). Eighty adult male rats were divided equally into four groups. Group I as a control group, group II included rats that received 250 mg/kg/day GE orally for eight weeks, group III included rats that received 200 mg/kg/day BPA orally for the same period and group IV included rats that received BPA in the same dose for the same duration concomitantly with GE. At the end of the experiment, blood samples were taken for hormonal essay and tissue samples were processed. Light and electron microscopic studies were done. Morphometric and statistical studies were carried out. Group III showed degenerative changes in the thyroid gland, decreased serum levels of T3 and T4 and a strong positive inducible nitric oxide synthase (iNOS) immune response. Group IV showed restoration of thyroid gland architecture and function. In conclusion, GE protected the thyroid structure from the damaging effect of BPA oxidative stress through its anti-oxidant effect, thus preserving thyroid activity. [ABSTRACT FROM AUTHOR]

This study was conducted to provide evidence, using in vitro and in silico testing methods, regarding the adverse effects of iprodione, a representative dichlorophenyl dicarboxamide fungicide, on the endocrine system. In the present study, we used the HeLa9903 stably transfected transactivation assay (OECD TG 455), 22Rv1/MMTV_GR‒KO androgen receptor transcriptional activation assay (OECD TG 458), and toxicity prediction using VEGA QSAR. Our results showed that iprodione had no estrogen receptor antagonistic or androgen receptor agonistic effects; however, iprodione was determined to be an estrogen receptor agonist (log PC10 value is less than − 9) and androgen receptor antagonist (log IC30 value is − 4.58) without intrinsic toxicity against the human cell lines used in this study. VEGA QSAR was used to evaluate five substances with structures similar to that of iprodione. Among them, four chemicals were found to have positive androgen receptor and aromatase activities and have been observed to be developmental toxicants. These results suggest that iprodione regulates steroid hormone receptor interactions and is a potential reproductive toxicant. [ABSTRACT FROM AUTHOR]

Diabetes and its complications significantly affect individuals' quality of life. The etiology of diabetes mellitus and its associated complications is complex and not yet fully understood. There is an increasing emphasis on investigating the effects of endocrine disruptors on diabetes, as these substances can impact cellular processes, energy production, and utilization, ultimately leading to disturbances in energy homeostasis. Mitochondria play a crucial role in cellular energy generation, and any impairment in these organelles can increase susceptibility to diabetes. This review examines the most recent epidemiological and pathogenic evidence concerning the link between endocrine disruptors and diabetes, including its complications. The analysis suggests that endocrine disruptor-induced mitochondrial dysfunction--characterized by disruptions in the mitochondrial electron transport chain, dysregulation of calcium ions (Ca2+), overproduction of reactive oxygen species (ROS), and initiation of signaling pathways related to mitochondrial apoptosis--may be key mechanisms connecting endocrine disruptors to the development of diabetes and its complications. [ABSTRACT FROM AUTHOR]

Azole fungicides are highly suspected endocrine disruptors (EDs) and are frequently detected in surface water. Among them, there are prochloraz (PCZ), a commonly used molecule for ED studies, and imazalil (IMZ), a highly suspected ED. Little is known about their toxicokinetic (TK) behavior in fish. Hence, research suggested that an improved risk assessment could be achieved by gaining insight into their TK behavior. The aim of this study is to understand and model the TK of both substances in different fish species, irrespective of the scheme of exposure. TK data from the literature were retrieved including different modes of exposure (per os and waterborne). In addition, two experiments on zebrafish exposed to either IMZ or PCZ were performed to address the lack of in vivo TK data. A physiologically based kinetic (PBK) model applied to IMZ and PCZ was developed, capable of modeling different exposure scenarios. The parameters of the PBK model were simultaneously calibrated on datasets reporting internal concentration in several organs in three fish species (original and literature datasets) by Bayesian methods (Monte Carlo Markov Chain). Model predictions were then compared to other experimental data (i.e., excluded from the calibration step) to assess the predictive performance of the model. The results strongly suggest that PCZ and IMZ are actively transported across the gills, resulting in a small fraction being effectively absorbed by the fish. The model's results also confirm that both molecules are extensively metabolized by the liver into mainly glucuronate conjugates. Overall, the model performances were satisfying, predicting internal concentrations in several key organs. On average, 90% of experimental data were predicted within a two-fold range. The PBK model allows the understanding of IMZ and PCZ kinetics profiles by accurately predicting internal concentrations in three different fish species regardless of the exposure scenario. This enables a proper understanding of the mechanism of action of EDs at the molecular initiating event (MIE) by predicting bioaccumulation in target organs, thus linking this MIE to a possible adverse outcome. [ABSTRACT FROM AUTHOR]

Glyphosate-based herbicides (GBH) are a widely used group of pesticides that have glyphosate (GLY) as main active compound and are used to control a wide range of weeds. Experimental and epidemiological studies point to neurotoxicity and endocrine disruption as main toxic effects. The aim of this study was to investigate the effects of developmental exposure to GLY and GBH on locomotor behavior, and the possible contribution of GR-mediated signaling. We used zebrafish (Danio rerio) larvae in a continuous exposure regimen to GLY or GBH in the rearing medium. Alongside TL wildtype, we used a mutant line carrying a mutation in the GR which prevents the GR from binding to DNA (grs357), as well as a transgenic strain expressing a variant of enhanced green fluorescent protein (d4eGFP) controlled by a promoter carrying multiple GR response elements (SR4G). We found that acute exposure to GBH, but not GLY, activates GR-mediated signaling. Using a continuous developmental exposure regime, we show that wildtype larvae exposed to GBH display decreased spontaneous activity and attenuated response to environmental stimuli, a pattern of alteration similar to the one observed in grs357 mutant larvae. In addition, developmental exposure to GBH has virtually no effects on the behavior of grs357 mutant larvae. Taken together, our data indicate that developmental exposure to GBH has more pronounced effects than GLY on behavior at 5 dpf, and that interference with GR-mediated signaling may have a relevant contribution. [ABSTRACT FROM AUTHOR]

Accumulating epidemiological evidence underscores the association between pervasive environmental factors and an increased risk of metabolic diseases. Environmental chemicals, recognized disruptors of endocrine and metabolic processes, may contribute to the global prevalence of metabolic disorders, including obesity. Acetyl tributyl citrate (ATHC), categorized as a citric acid ester plasticizer, serves as a substitute for di-(2-ethylhexyl) phthalate (DEHP) in various everyday products. Despite its widespread use and the increasing risk of exposure in humans and animals due to its high leakage rates, information regarding the safety of exposure to environmentally relevant doses of ATHC remains limited. This study aimed to investigate the potential impact of ATHC exposure on metabolic homeostasis. Both in vivo and in vitro exposure models were used to characterize the effects induced by ATHC exposure. C57BL/6 J male mice were subjected to a diet containing ATHC for 12 weeks, and metabolism-related parameters were monitored and analyzed throughout and after the exposure period. Results indicated that sub-chronic dietary exposure to ATHC induced an increase in body fat percentage, elevated serum lipid levels, and increased lipid content in the liver tissue of mice. Furthermore, the effect of ATHC exposure on murine hepatocytes were examined and results indicated that ATHC significantly augmented lipid levels in AML12 hepatocytes, disrupting energy homeostasis and altering the expression of genes associated with fatty acid synthesis, uptake, oxidation, and secretion pathways. Conclusively, both in vivo and in vitro results suggest that exposure to low levels of ATHC may be linked to an elevated risk of obesity and fatty liver in mice. The potential implications of ATHC on human health warrant comprehensive evaluation in future studies. [ABSTRACT FROM AUTHOR]

Phthalates, such as di-n-butyl phthalate (DBP) and di-isopentyl phthalate (DiPeP), are pollutants with a high potential for endocrine disruption. This study aimed to evaluate parameters of endocrine disruption in specimens of the Neotropical fish Rhamdia quelen exposed to DBP and DiPeP through their food. After 30 days of exposure, the fish were anesthetized and then euthanized, and blood, hypothalamus, liver, and gonads were collected. DBP caused statistically significant alterations in the serotoninergic system of males (5 and 25 ng/g) and females (5 ng/g) of R. quelen and it increased testosterone levels in females (25 ng/g). DiPeP significantly altered the dopaminergic system in females, reduced plasma estradiol levels (125 ng/g) and hepatic vitellogenin expression (25 ng/g), and changed the antioxidant system in gonads (125 ng/g). The results suggest that DBP and DiPeP may have different response patterns in females, with the former being androgenic and the latter being anti-estrogenic. These findings provide additional evidence regarding the molecular events involving DBP and DiPeP in the endocrine disruption potential in juvenile specimens of Rhamdia quelen. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), an endocrine-disrupting chemical, poses significant health problems due to its induction of oxidative stress, inflammation, etc. Whereas Ficus exasperata Vahl leaf (FEVL) was reported for its ethnopharmacological properties against several ailments owing to its antioxidant, anti-inflammatory properties, etc. Here, we aim to elucidate and identify the bioactive compounds of aqueous extract of FEVL (AEFEVL) against BPA-induced toxicity using in vivo and in silico assessments. To determine the BPA toxicity mechanism and safe doses of AEFEVL, graded doses of BPA (0–400 μM) and AEFEVL (0–2.0 mg/10 g diets) were separately fed to flies to evaluate survival rates and specific biochemical markers. The mitigating effect of AEFEVL (0.5 and 1.0 mg/10 g diet) against BPA (100 and 200 μM)-induced toxicity in the flies after 7-day exposure was also carried out. Additionally, molecular docking analysis of BPA and BPA-o-quinone (BPAQ) against selected antioxidant targets, and HPLC–MS-revealed AEFEVL compounds against Keap-1 and IKKβ targets, followed by ADMET analysis, was conducted. Emergence rate, climbing ability, acetylcholinesterase, monoamine oxidase-B, and glutathione-S-transferase activities, and levels of total thiols, non-protein thiols, nitric oxide, protein carbonyl, malondialdehyde, and cell viability were evaluated. BPA-induced altered biochemical and behavioral parameters were significantly mitigated by AEFEVL in the flies (p < 0.05). BPAQ followed by BPA exhibited higher inhibitory activity, and epigallocatechin (EGC) showed the highest inhibitory activity among the AEFEVL compounds with desirable ADMET properties. Conclusively, our findings revealed that EGC might be responsible for the mitigative effect displayed by AEFEVL in BPA-induced toxicity in D. melanogaster. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an endocrine disruptor and poses serious threats to human health, and widespread concern has been raised regarding its effective removal from the environment. In this work, an eco-friendly surface molecularly imprinted composite (MIL-100(Fe)@MIP) was successfully fabricated in the green solvent of water and further achieved the fast and effective removal of BPA. The maximum adsorption capacity of BPA bound to MIL-100(Fe)@MIP was 15.45 mg g−1, and the adsorption behavior was adequately described with the Langmuir model. MIL-100(Fe)@MIP acquired fast adsorption of BPA, and the equilibrium adsorption capacity achieved 95% within 10 min. The adsorption process better matches the pseudo-second-order model. As a solid phase sorbent, MIL-100(Fe)@MIP was successfully applied to rapidly and efficiently remove BPA from five real samples, which included disposable food containers, canned yellow peach, orange juice, soybean milk and teabags, and the recoveries ranged from 80.67% to 100.58%. Furthermore, MIL-100(Fe)@MIP exhibited excellent reusability for 20 cycles. Hence, the developed MIL-100(Fe)@MIP is an eco-friendly and promising adsorbent that can effectively and rapidly remove BPA from the environment. [ABSTRACT FROM AUTHOR]

Across the globe, many species of insects are facing population decline. This is largely driven by anthropogenic changes to the environment, including the widespread exposure of invertebrates to endocrine disrupting chemicals (EDCs), which impair fertility. To test whether generations of Drosophila melanogaster born from parents exposed to a common dietary EDC, equol, could recover reproductive function, we quantified the reproductive capacity of the two subsequent generations. Using a novel suite of flow cytometry assays to assess sperm functionality in real time, we find that sperm function is compromised across three generations, even after non-exposed in individuals contribute to the breeding population. Though the sex ratio alters in response to EDC exposure, favouring the survival of female offspring, most lineages with ancestral EDC exposure exhibit persistent subfertility in both the male and female. Male offspring with ancestral EDC exposure present with reduced fertility and dysfunctional spermatozoa, whereby spermatozoa are metabolically stressed, lack DNA integrity and present with permanent epigenetic alterations. Across generations, male and female offspring demonstrate distinct patterns of reproductive characteristics, depending upon the specific lineage of EDC exposure. Our results illustrate how dietary EDCs present in agricultural plants could promote transgenerational subfertility and contribute to declining insect populations. [ABSTRACT FROM AUTHOR]

This comprehensive review critically examines the detrimental impacts of endocrine-disrupting chemicals (EDCs) on bone health, with a specific focus on substances such as bisphenol A (BPA), per- and polyfluoroalkyl substances (PFASs), phthalates, and dioxins. These EDCs, by interfering with the endocrine system's normal functioning, pose a significant risk to bone metabolism, potentially leading to a heightened susceptibility to bone-related disorders and diseases. Notably, BPA has been shown to inhibit the differentiation of osteoblasts and promote the apoptosis of osteoblasts, which results in altered bone turnover status. PFASs, known for their environmental persistence and ability to bioaccumulate in the human body, have been linked to an increased osteoporosis risk. Similarly, phthalates, which are widely used in the production of plastics, have been associated with adverse bone health outcomes, showing an inverse relationship between phthalate exposure and bone mineral density. Dioxins present a more complex picture, with research findings suggesting both potential benefits and adverse effects on bone structure and density, depending on factors such as the timing and level of exposure. This review underscores the urgent need for further research to better understand the specific pathways through which EDCs affect bone health and to develop targeted strategies for mitigating their potentially harmful impacts. [ABSTRACT FROM AUTHOR]

The zebrafish (Danio rerio) is becoming a critical component of new approach methods (NAMs) in chemical risk assessment. As a whole organism in vitro NAM, the zebrafish model offers significant advantages over individual cell-line testing, including toxicokinetic and toxicodynamic competencies. A transcriptomic approach not only allows for insight into mechanism of action for both apical endpoints and unobservable adverse outcomes, but also changes in gene expression induced by lower, environmentally relevant concentrations. In this study, we used a larval zebrafish model to assess the behavioral and transcriptomic alterations caused by subphenotypic concentrations of 2 chemicals with the same structural backbone, the endocrine-disrupting chemicals bisphenol A and tetrabromobisphenol A. Following assessment of behavioral toxicity, we used a transcriptomic approach to identify molecular pathways associated with previously described phenotypes. We also determined the transcriptomic point of departure for each chemical by modeling gene expression changes as continuous systems which allows for the identification of a single concentration at which toxic effects can be predicted. This can then be investigated with confirmatory cell-based testing in an integrated approach to testing and assessment to determine risk to human health and the environment with greater confidence. This paper demonstrates the impact of using a multi-faceted approach for evaluating the physiological and neurotoxic effects of exposure to structurally related chemicals. By comparing phenotypic effects with transcriptomic outcomes, we were able to differentiate, characterize, and rank the toxicities of related bisphenols, which demonstrates methodological advantages unique to the larval zebrafish NAM. [ABSTRACT FROM AUTHOR]

The placenta operates during gestation as the primary communication organ between the mother and fetus. It is essential for gas, nutrient exchange, and fetal waste transfer. The placenta also produces a wide range of hormones and other factors that influence maternal physiology, including survival and activity of the corpus luteum of the ovary, but the means whereby the placenta shapes fetal development remain less clear, although the fetal brain is thought to be dependent upon the placenta for factors that play roles in its early differentiation and growth, giving rise to the term "placenta–brain axis". Placental hormones transit via the maternal and fetal vasculature, but smaller placental molecules require protection from fetal and maternal metabolism. Such biomolecules include small RNA, mRNA, peptides, lipids, and catecholamines that include serotonin and dopamine. These compounds presumably shuttle to maternal and fetal systems via protective extracellular vesicles (EVs). Placental EVs (pEVs) and their components, in particular miRNA (miRs), are known to play important roles in regulating maternal systems, such as immune, cardiovascular, and reproductive functions. A scant amount is known about how pEVs affect fetal cells and tissues. The composition of pEVs can be influenced by gestational diseases. This review will provide critical insight into the roles of pEVs as the intermediary link between maternal and fetal systems, the impact of maternal pathologies on pEV cargo contents, and how an understanding of biomolecular changes within pEVs in health and disease might be utilized to design early diagnostic and mitigation strategies to prevent gestational diseases and later offspring disorders. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), as a typical endocrine disruptor, can cause serious harm to human health. In order to solve the limitation of biological enzyme method in the degradation of BPA in actual water, we successfully prepared a photo-enzyme-coupled catalyst CN-HRP@ZIP by in situ generation of a metal–organic skeleton coated with HRP on the carbon nitride surface. The photo-enzymatic synergy of the material and the low mass transfer resistance caused by the two-dimensional ZIP make CN-HRP@ZIP can achieve 100% degradation of BPA at 40 min. The degradation rate was 3.92 times that of CN and 1.65 times that of CN-HRP@ZIF, respectively. The immobilization of the enzyme broadened the degradation pathway and enhanced the resistance to anionic interference by enzyme specificity. The direct conversion of hydrogen peroxide by the enzyme and the indirect enhancement of photocatalytic superoxide radical production increased the concentration of superoxide radicals in the system, and CN-HRP@ZIP maintained a high degradation rate of more than 90% in five cycles. The stability of the enzymatic activity of the material was much higher than that of the free enzyme under extreme pH, high temperature, and organic solvent immersion. These studies provide a new reference for the application of photo-enzymatic synergistic degradation in industrial wastewater treatment. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) and dioxin are persistent endocrine disrupting chemicals (EDCs) and have been associated with an increased risk of metabolic syndrome (MetS). The aim of this systematic review and meta-analysis was to assess the associations of PCBs and dioxin with MetS and its risk factors, including obesity, hypertriglyceridaemia (HTG), hypertension (HTN) and diabetes mellitus (DM). We searched three electronic databases for epidemiological studies concerning PCBs and dioxin with MetS published up to the end of 2023. Meta-analysis was performed for MetS itself and each of the MetS risks based on a random-effects meta-analysis model, and odds ratios (ORs) with 95% confidence intervals (CIs) were obtained. Publication bias was assessed based on Egger's test. Eleven studies were included from three databases up to 2023. There were 40,528 participants aged 18–89, where 18–100% of them were males, included in our meta-analysis. The meta-analysis results showed a strong association between PCB exposure and DM (OR = 3.593, 95% CI 2.566, 5.031), while most of the risk factors for MetS, including obesity (OR = 1.875, 95% CI 0.883, 3.979), HTN (OR = 1.335, 95% CI 0.902, 1.976) and HTG (OR = 1.611, 95% CI 0.981, 2.643), were weakly associated with PCB. Furthermore, both PCBs (OR = 1.162, 95% CI 0.994, 1.357) and dioxin (OR = 2.742, 95% CI 1.936, 3.883) were found to be weakly and strongly associated with MetS, respectively. Meta-regression analysis showed that DM in the Asian population is associated with PCB exposure, while HTG in the Northern American population is associated with PCB exposure. Our meta-analysis has demonstrated a strong relationship between DM and PCBs, while the relationship between PCBs with MetS and other risk factors is less pronounced. Additionally, MetS is weakly associated with dioxin exposure. To improve primary care outcomes, healthcare providers should consider incorporating the assessment of patients' risk of exposure to PCBs and dioxins into their evaluation procedures for more targeted medical interventions. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is an endocrine disorder whose etiology is not well understood and affecting 9–18% of women in reproductive age. We investigated the protective effects of phloretin against the PCOS, induced Bisphenol A (BPA) on prepubertal rat ovaries. This study started on female rats on the postnatal 28th day via subcutaneous injection by dissolving the compounds in corn oil at 30 min intervals, starting with phloretin, and followed by BPA. The dose of BPA was 50 mg/kg/day, and the doses of phloretin were 0.5, 5, and 50 mg/kg/day. Treatments were administered every day for 15 days. Likewise corn oil, BPA and testosterone propionate were given by the same way. BPA exposed groups, it has been observed that there are many cystic follicles in the ovary and their morphology has changed. Similarly, prolonged diestrus phases was observed in the smear cycle. The CYP11A1 and CYP17A enzymes stained intensively on the BPA group whereas these enzymes were stained weakly in the BPA + 5 and 50 mg/kg phloretin groups. In PCOS, induced by BPA, the cystic follicles were recorded on the ovaries whereas it was decreased in the BPA + phloretin groups. Prepubertal exposure to BPA was associated with decreased serum luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels, increased estrogen (ERRα) and dihydrotestosterone (DHT) levels in testosterone propiyonat and BPA + phloretin (0.5 mg/kg/day) groups. In conclusion, in rat model, phloretin has positive effects against BPA induced polycystic ovarian syndrome, also it caused positive effects on ovarian tissue and hormone secretion. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting environmental chemicals are a public health concern, particularly fetal exposure to Bisphenol derivatives. This study aimed to assess fetal exposure to Bisphenol derivatives (BPA, BPF, and BPS) by measuring their levels in cord blood and investigating their association with plastic material used in daily life as well as cord blood TSH and free L-thyroxine (fT4) levels. In this descriptive study, a questionnaire with a face-to-face interview was administered before birth, and cord blood samples were taken immediately after delivery. The mean levels of BPA, BPF, TSH, and fT4 were measured as 10.69 ± 2.39 ng/ml, 3.80 ± 0.58 ng/ml; 2.36 ± 0.23 µIU/ml, and 14.18 ± 0.53 pg/ml, respectively, in a total of 104 cord blood samples. All BPS levels remained below the detection limit. Linear regression analysis revealed a positive association between birth weight and cord blood BPA concentration (β = 0.26; p = 0.02). Further research on maternal exposure during the fetal and neonatal period is critical for public health. [ABSTRACT FROM AUTHOR]

In this review article, the research works covering the analytical determination of bisphenol A (BPA) and its structural analogues published from 2018 to present (February 2024) were examined. The review offers an overview of the concentration levels of these xenoestrogens in food and beverages, and discusses concerns that these may possibly pose to the human health and scrutinises, from an analytical perspective, the main biomonitoring approaches that are applied. This comes as a natural evolution of a previous review that covered the same topic but in earlier years (up to 2017). As compared to the past, while the volume of published literature on this topic has not necessarily decreased, the research studies are now much more homogeneous in terms of their geographical origin, i.e., Southern Europe (mainly Italy and Spain). For this reason, an estimated daily intake of the European population could not be calculated at this time. In terms of the analytical approaches that were applied, 67% of the research groups exploited liquid chromatography (LC), with a detection that was prevalently (71%) afforded by mass spectrometry, with over one-fourth of the research teams using fluorescence (26%) and a minority (3%) detecting the analytes with diode array detection. One-third of the groups used gas chromatography (GC)–mass spectrometry achieving comparatively superior efficiency as compared to LC. Derivatisation was performed in 59% of the GC studies to afford more symmetrical signals and enhanced sensitivity. Although the contamination levels are well below the threshold set by governments, routinely biomonitoring is encouraged because of the possible accumulation of these contaminants in the human body and of their interplay with other xenoestrogens. [ABSTRACT FROM AUTHOR]

BACKGROUND: Seafood consumers are widely exposed to diclofenac due to the high contamination levels often present in aquatic organisms. It is a potential risk to public health due its endocrine disruptor properties. Limited information is available about diclofenac behavior after food digestion to enable a more realistic scenario of consumer exposure. This study aimed to evaluate cooking effects on diclofenac levels, and determine diclofenac bioaccessibility by an in vitro digestion assay, using commercial fish species (seabass and white mullet) as models. The production of the main metabolite 4′‐hydroxydiclofenac was also investigated. Fish hamburgers were spiked at two levels (150 and 1000 ng g−1) and submitted to three culinary treatments (roasting, steaming and grilling). RESULTS: The loss of water seems to increase the diclofenac levels after cooking, except in seabass with higher levels. The high bioaccessibility of diclofenac (59.1–98.3%) observed in both fish species indicates that consumers' intestines are more susceptible to absorption, which can be worrisome depending on the level of contamination. Contamination levels did not affect the diclofenac bioaccessibility in both species. Seabass, the fattest species, exhibited a higher bioaccessibility of diclofenac compared to white mullet. Overall, cooking decreased diclofenac bioaccessibility by up to 40% in seabass and 25% in white mullet. The main metabolite 4′‐hydroxydiclofenac was not detected after cooking or digestion. CONCLUSION: Thus, consumption of cooked fish, preferentially grilled seabass and steamed or baked white mullet are more advisable. This study highlights the importance to consider bioaccessibility and cooking in hazard characterization studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a compound known for its direct action on the prostate. Prostatic morphogenesis is a critical period when interference by any compound could permanently damage the organ. As such, the present study evaluated the morphological aspects resulting from gestational and lactational administration of BPA, indole-3-carbinol (I3C) and genistein (GEN) in prepubescent male rats. Pregnant Sprague Dawley females were allocated into 4 experimental groups and received the following: C: Control (no treatment); B: BPA (10 µg/Kg); BG: BPA+GEN (5 mg/Kg); BI: BPA+I3C (20 mg/Kg) from gestation day (GD) 17 to postnatal day (PND) 21. After euthanasia on PND22, the prostate was collected and processed. When administered alone, BPA reduced the stromal compartment when compared to group C (P = 0.039). This decline was reversed in the groups submitted to GEN (P = 0.019) or I3C (P = 0.017). The groups treated with BPA (P < 0.0001) and the phytoestrogens (P < 0.0001) exhibited decreased epithelial height in relation to the control group. These changes were observed in stereological and morphometric analyses, but not in fractal analysis (P = 0.569). The area occupied by collagen increased in groups treated with BPA (P < 0.0001) and phytoestrogens (P < 0.0001) in relation to controls, while collagen distribution values were higher in all the treated groups (P < 0.0001), according to fractal analysis. Thus, BPA induced prostrate stroma remodeling with no influence from the phytoestrogens, which may affect glandular development and cause histopathological changes in adulthood. [ABSTRACT FROM AUTHOR]

Polycystic Ovary Syndrome (PCOS) is a multifaceted condition influenced by genetic, hormonal, and environmental factors. Among environmental factors, Bisphenol A (BPA)—a recognized endocrine disruptor—has been implicated in the development of PCOS. The study aimed to compare BPA levels in women diagnosed with PCOS with those in healthy controls, using the high-performance liquid chromatography (HPLC) technique. The study involved 80 women diagnosed with PCOS and 50 healthy control participants. Demographic and biochemical parameters were recorded, including age, Body Mass Index (BMI), and levels of testosterone, estradiol, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Prolactin (PRL), Dehydroepiandrosterone Sulfate (DHEA-S), Thyroid Stimulating Hormone (TSH), and Insulin Resistance as measured by the Homeostatic Model Assessment (HOMA-IR). Furthermore, BPA levels were measured using the HPLC technique. Women with PCOS exhibited significantly higher mean age and BMI compared to healthy controls (p = 0.01, p < 0.0001, respectively). Additionally, higher levels of testosterone (p = 0.04), LH (p = 0.03) and BPA (p < 0.0001) were observed in women with PCOS. However, estradiol, FSH, PRL, LH/FSH ratio, DHEA-S, and TSH levels were not significantly different between the two groups. HOMA-IR levels were not recorded for the control group. A notable positive relationship emerged between Bisphenol A and luteinizing hormone (LH) levels (r = 0.23, p = 0.03), also significant negative correlation appeared between Bisphenol A and thyroid-stimulating hormone (TSH) levels. This study found that women with PCOS have elevated BPA levels compared with healthy controls, showing a need for further research on the relationship between BPA exposure and the development of PCOS. [ABSTRACT FROM AUTHOR]

Background Phthalates are additives used as plasticizers among other uses, classified as endocrine disruptors and may contribute to some metabolic disorders. The aim of this work was to determine the effect of the exposure of diethyl phthalate (DEP) and dibutyl phthalate (DBP) on cell viability and reactive oxygen species (ROS) production, as well as the regulation of sirloins in HepG2 cells. Methods HepG2 cells were exposed to DEP or DBP at 0.1, 1, 10 and 100 μg/mL, and after 48 or 72 h the gene and protein expression of sirtuins was quantified by qRT-PCR and Western-Blot, respectively. Results Results showed that even at a low concentration of 0.1 μg/mL DEP affected the expression of Sirt3 and Sirt4, whereas DBP at 0.1 μg/mL affected Sirt3 and Sirt5 gene expression. Protein analysis showed a reduction in Sirt1 levels at a DEP concentration of 1 μg/mL and higher, while DBP at higher dose (100 μg/mL) decreased Sirt3 protein levels. Cell viability decreased by 20% only at higher dose (100 μg/mL) and ROS production increased at 10 and 100 μg/mL for both phthalates. Conclusion These findings indicate that exposure to low concentrations (0.1 μg/mL) of DEP or DBP can negatively influence the expression of some sirtuins. [ABSTRACT FROM AUTHOR]

The blood-brain barrier (BBB) is an extensive capillary network that protects the brain from environmental and metabolic toxins while limiting drug delivery to the central nervous system (CNS). The ATP-binding cassette transporter breast cancer resistance protein (Bcrp) reduces drug delivery across the BBB by actively transporting its clinical substrates back into peripheral circulation before their entry into the CNS compartment. 17β-Estradiol (E2)-elicited changes in Bcrp transport activity and expression have been documented previously. We report a novel signaling mechanism by which E2 decreases Bcrp transport activity in mouse brain capillaries via rapid nongenomic signaling through estrogen receptor α. We extended this finding to investigate the effects of different endocrine-disrupting compounds (EDCs) and selective estrogen receptor modulators (SERMs) on Bcrp transport function. We also demonstrate sex-dependent expression of Bcrp and E2-sensitive Bcrp transport activity at the BBB ex vivo. This work establishes an explanted tissue-based model by which to interrogate EDCs and SERMs as modulators of nongenomic estrogenic signaling with implications for sex and hormonal regulation of therapeutic delivery into the CNS. [ABSTRACT FROM AUTHOR]