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Abstract 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.

In catalytic tests, the results have shown that almost all the BPAF was removed within 30 min when the dosage of Co3O4@BiOI and sodium persulfate (PS) was 0.15 g and 0.1 mM, respectively. Acid conditions inhibited BPAF degradation, but the inclusion of a precise concentration of bicarbonate ions (HCO3−) promoted degradation. The presence of chloride (Cl−), sulfate ions (SO42−), and a high concentration of HCO3− inhibited the degradation process, whereas the addition of nitrate ions (NO3−) had a minor effect on the catalytic process. The presence of free radicals (sulfate (SO4•−), hydroxyl (•OH), and superoxide (O2•−)) and the non-free radical singlet oxygen (1O2) in the Co3O4@BiOI/PS system was determined by electron paramagnetic resonance (EPR) and quenching tests. We propose that the Co(II)/Co(III) and Bi(III)/Bi(V) redox pairs simultaneously activate PS where the Co3O4 and BiOI components work synergistically to promote the rapid oxidative degradation of BPAF in water. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals (EDCs) impair growth and development. While EDCs can occur naturally in aquatic ecosystems, they are continuously introduced through anthropogenic activities such as industrial effluents, pharmaceutical production, wastewater, and mining. To elucidate the chronic toxicological effects of endocrine-disrupting chemicals (EDCs) on aquatic organisms, we collected experimental data from a standardized chronic exposure test using Daphnia magna (D. magna), individuals of which were exposed to a potential EDC, trinitrotoluene (TNT). The chronic toxicity effects of this compound were explored through differential gene expression, gene ontology, network construction, and putative adverse outcome pathway (AOP) proposition. Our findings suggest that TNT has detrimental effects on the upstream signaling of Tcf/Lef, potentially adversely impacting oocyte maturation and early development. This study employs diverse bioinformatics approaches to elucidate the gene-level toxicological effects of chronic TNT exposure on aquatic ecosystems. The results provide valuable insights into the molecular mechanisms of the adverse impacts of TNT through network construction and putative AOP proposition. [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]

Non-persistent endocrine-disrupting chemicals (EDCs) are of significant concern due to their reproductive toxicity. Previous research reported a relationship between a single type of EDCs and endometriosis. Yet, evidence regarding mixed exposure of multiple categories of EDCs is scarce. Between 2014 and 2018, our hospital-based case-control study recruited 238 endometriosis cases diagnosed by laparoscopy and 296 normal controls in China. Seventeen non-persistent EDCs (phthalates and bisphenols) were measured in urine. The association of single EDC with endometriosis was estimated using logistic regression, while the association between EDC mixture and endometriosis was modeled by Bayesian kernel machine regression (BKMR), quantile-based g-computation (q-gcomp), and principal component analysis (PCA). Consistent results were observed in both single and mixture models where phthalates and bisphenols were associated with increased risk of endometriosis (mixture effect: adjusted odds ratio (aOR)=1.44, 1.22–1.70) and the major contributors were bisphenol A (BPA) and the metabolites of di(2-ethylhexyl) phthalate (DEHP). Interaction analysis showed that bisphenols exhibited significant synergistic interactions with phthalates. Our results suggest that non-persistent EDCs are associated with endometriosis but the underlying mechanisms remain to be elucidated. Our finding may have important public health implications in preventing endometriosis.

Abstract Background Recent studies have shown that prenatal BPA exposure altered the transcriptome profiles of autism-related genes in the offspring’s hippocampus, disrupting hippocampal neuritogenesis and causing male-specific deficits in learning. However, the sex differences in the effects of prenatal BPA exposure on the developing prefrontal cortex, which is another brain region highly implicated in autism spectrum disorder (ASD), have not been investigated. Methods We obtained transcriptome data from RNA sequencing analysis of the prefrontal cortex of male and female rat pups prenatally exposed to BPA or control and reanalyzed. BPA-responsive genes associated with cortical development and social behaviors were selected for confirmation by qRT-PCR analysis. Neuritogenesis of primary cells from the prefrontal cortex of pups prenatally exposed to BPA or control was examined. The social behaviors of the pups were assessed using the two-trial and three-chamber tests. The male-specific impact of the downregulation of a selected BPA-responsive gene (i.e., Sema5a) on cortical development in vivo was interrogated using siRNA-mediated knockdown by an in utero electroporation technique. Results Genes disrupted by prenatal BPA exposure were associated with ASD and showed sex-specific dysregulation. Sema5a and Slc9a9, which were involved in neuritogenesis and social behaviors, were downregulated only in males, while Anxa2 and Junb, which were also linked to neuritogenesis and social behaviors, were suppressed only in females. Neuritogenesis was increased in males and showed a strong inverse correlation with Sema5a and Slc9a9 expression levels, whereas, in the females, neuritogenesis was decreased and correlated with Anxa2 and Junb levels. The siRNA-mediated knockdown of Sema5a in males also impaired cortical development in utero. Consistent with Anxa2 and Junb downregulations, deficits in social novelty were observed only in female offspring but not in males. Conclusion This is the first study to show that prenatal BPA exposure dysregulated the expression of ASD-related genes and functions, including cortical neuritogenesis and development and social behaviors, in a sex-dependent manner. Our findings suggest that, besides the hippocampus, BPA could also exert its adverse effects through sex-specific molecular mechanisms in the offspring’s prefrontal cortex, which in turn would lead to sex differences in ASD-related neuropathology and clinical manifestations, which deserves further investigation.

Amphibians are the most threatened vertebrate class globally. Multiple factors have been implicated in their global decline, and it has been hypothesized that interactions between stressors may be a major cause. Increased ultraviolet (UV) radiation, as a result of ozone depletion, has been identified as one such stressor. Exposure to UV radiation has been shown to have detrimental effects on amphibians and can exacerbate the effects of other stressors, such as chemical pollutants. Chemical pollution has likewise been recognized as a major factor contributing to amphibian declines, particularly, endocrine‐disrupting chemicals. In this regard, 17β‐trenbolone is a potent anabolic steroid used in the agricultural industry to increase muscle mass in cattle and has been repeatedly detected in the environment where amphibians live and breed. At high concentrations, 17β‐trenbolone has been shown to impact amphibian survival and gonadal development. In the present study, we investigated the effects of environmentally realistic UV radiation and 17β‐trenbolone exposure, both in isolation and in combination, on the morphology and behavior of tadpoles (Limnodynastes tasmaniensis). We found that neither stressor in isolation affected tadpoles, nor did we find any interactive effects. The results from our 17β‐trenbolone treatment are consistent with recent research suggesting that, at environmentally realistic concentrations, tadpoles may be less vulnerable to this pollutant compared to other vertebrate classes. The absence of UV radiation–induced effects found in the present study could be due to species‐specific variation in susceptibility, as well as the dosage utilized. We suggest that future research should incorporate long‐term studies with multiple stressors to accurately identify the threats to, and subsequent consequences for, amphibians under natural conditions. Environ Toxicol Chem 2024;43:1615–1626. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

During the last decades, endocrine-disrupting chemicals (EDCs) have attracted the attention of the scientific community, as a result of a deepened understanding of their effects on human health. These compounds, which can reach populations through the food chain and a number of daily life products, are known to modify the activity of the endocrine system. Regarding vulnerable groups like pregnant mothers, the potential damage they can cause increases their importance, since it is the health of two lives that is at risk. EDCs can affect the gestation process, altering fetal development, and eventually inducing the appearance of many disorders in their childhood and/or adulthood. Because of this, several of these substances have been studied to clarify the influence of their prenatal exposure on the cognitive and psychomotor development of the newborn, together with the appearance of non-communicable diseases and other disorders. The most novel research on the subject has been gathered in this narrative review, with the aim of clarifying the current knowledge on the subject. EDCs have shown, through different studies involving both animal and human investigation, a detrimental effect on the development of children exposed to the during pregnancy, sometimes with sex-specific outcomes. However, some other studies have failed to find these associations, which highlights the need for deeper and more rigorous research, that will provide an even more solid foundation for the establishment of policies against the extended use of these chemicals. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that prenatal BPA exposure altered the transcriptome profiles of autism-related genes in the offspring's hippocampus, disrupting hippocampal neuritogenesis and causing male-specific deficits in learning. However, the sex differences in the effects of prenatal BPA exposure on the developing prefrontal cortex, which is another brain region highly implicated in autism spectrum disorder (ASD), have not been investigated. Methods: We obtained transcriptome data from RNA sequencing analysis of the prefrontal cortex of male and female rat pups prenatally exposed to BPA or control and reanalyzed. BPA-responsive genes associated with cortical development and social behaviors were selected for confirmation by qRT-PCR analysis. Neuritogenesis of primary cells from the prefrontal cortex of pups prenatally exposed to BPA or control was examined. The social behaviors of the pups were assessed using the two-trial and three-chamber tests. The male-specific impact of the downregulation of a selected BPA-responsive gene (i.e., Sema5a) on cortical development in vivo was interrogated using siRNA-mediated knockdown by an in utero electroporation technique. Results: Genes disrupted by prenatal BPA exposure were associated with ASD and showed sex-specific dysregulation. Sema5a and Slc9a9, which were involved in neuritogenesis and social behaviors, were downregulated only in males, while Anxa2 and Junb, which were also linked to neuritogenesis and social behaviors, were suppressed only in females. Neuritogenesis was increased in males and showed a strong inverse correlation with Sema5a and Slc9a9 expression levels, whereas, in the females, neuritogenesis was decreased and correlated with Anxa2 and Junb levels. The siRNA-mediated knockdown of Sema5a in males also impaired cortical development in utero. Consistent with Anxa2 and Junb downregulations, deficits in social novelty were observed only in female offspring but not in males. Conclusion: This is the first study to show that prenatal BPA exposure dysregulated the expression of ASD-related genes and functions, including cortical neuritogenesis and development and social behaviors, in a sex-dependent manner. Our findings suggest that, besides the hippocampus, BPA could also exert its adverse effects through sex-specific molecular mechanisms in the offspring's prefrontal cortex, which in turn would lead to sex differences in ASD-related neuropathology and clinical manifestations, which deserves further investigation. Highlights: Prenatal BPA exposure altered the transcriptome-interactome profiles of ASD-related genes in the offspring's prefrontal cortex in a sex-specific pattern. Primary prefrontal cortical neurons isolated from male pups prenatally exposed to BPA exhibited increased neuritogenesis, while that was decreased in the cells from female pups. Deficits in social novelty were observed only in female pups prenatally exposed to BPA but not in males. Sema5a and Slc9a9 were reduced and showed an inverse correlation with neuritogenesis only in male pups exposed to BPA but not in females, suggesting that these genes may negatively regulate neuritogenesis in a male-specific manner. Anxa2 and Junb were suppressed and showed a correlation with impaired social novelty behavior only in female pups exposed to BPA but not in males, suggesting that these genes are involved in BPA-mediated social impairment in females only. siRNA-mediated knockdown of Sema5a in male embryos increased neuronal migration in the developing cortex. [ABSTRACT FROM AUTHOR]

Background: Spironolactone (SPI) is a diuretic widely used to treat cardiovascular diseases (CVD) and is non-specific for mineralocorticoid receptors (MR) and with an affinity for progesterone (PR) and androgen (AR) receptors. Since 2009, it has been suggested that pharmaceuticals are emerging contaminants (called EDC), and recently, it was reported that most EDC are AR and MR antagonists and estrogen receptors (ER) agonists. Concerning SPI, endocrine-disrupting effects were observed in female western mosquitofish, but there are still no data regarding the SPI effects as a possible human EDC. Methods: In this work, aortic rings were used to analyze the contractility effects of SPI and the mode of action concerning the involvement of Ca2+ channels and endothelial pathways. Moreover, cytotoxic effects were analyzed by MTT assays. Results: SPI induces vasodilation in the rat aorta by endothelium-dependent mechanisms involving NO and by endothelium-independent mechanisms blocking Ca2+ channels. Moreover, a non-monotonic effect characteristic of EDC was observed for SPI-induced decrease in cell viability. Conclusions: Our findings suggest that SPI may act as an EDC at a human level. However, ex vivo studies with human arteries should be carried out to better understand this drug’s implications for human health and future generations.

Background: Spironolactone (SPI) is a diuretic widely used to treat cardiovascular diseases (CVD) and is non-specific for mineralocorticoid receptors (MR) and with an affinity for progesterone (PR) and androgen (AR) receptors. Since 2009, it has been suggested that pharmaceuticals are emerging contaminants (called EDC), and recently, it was reported that most EDC are AR and MR antagonists and estrogen receptors (ER) agonists. Concerning SPI, endocrine-disrupting effects were observed in female western mosquitofish, but there are still no data regarding the SPI effects as a possible human EDC. Methods: In this work, aortic rings were used to analyze the contractility effects of SPI and the mode of action concerning the involvement of Ca2+ channels and endothelial pathways. Moreover, cytotoxic effects were analyzed by MTT assays. Results: SPI induces vasodilation in the rat aorta by endothelium-dependent mechanisms involving NO and by endothelium-independent mechanisms blocking Ca2+ channels. Moreover, a non-monotonic effect characteristic of EDC was observed for SPI-induced decrease in cell viability. Conclusions: Our findings suggest that SPI may act as an EDC at a human level. However, ex vivo studies with human arteries should be carried out to better understand this drug's implications for human health and future generations. [ABSTRACT FROM AUTHOR]

Glyphosate-based herbicides (GBH) are the most widely used pesticides globally. Studies have indicated that they may increase the risk of various organic dysfunctions. Herein, we verified whether exposure to GBH during puberty increases the susceptibility of male and female mice to obesity when they are fed a high-fat diet (HFD) in adulthood. From the 4th–7th weeks of age, male and female C57Bl/6 mice received water (CTL group) or 50 mg GBH /kg body weight (BW; GBH group). From the 8th–21st weeks of age, the mice were fed a standard diet or a HFD. It was found that pubertal GBH exposure exacerbated BW gains and hyperphagia induced by HFD, but only in female GBH-HFD mice. These female mice also exhibited high accumulation of perigonadal and subcutaneous fat, as well as reduced lean body mass. Both male and female GBH-HFD displayed hypertrophic white adipocytes. However, only in females, pubertal GBH exposure aggravated HFD-induced fat accumulation in brown adipocytes. Furthermore, GBH increased plasma cortisol levels by 80% in GBH-HFD males, and 180% in GBH-HFD females. In conclusion, pubertal GBH exposure aggravated HFD-induced obesity, particularly in adult female mice. This study provides novel evidence that GBH misprograms lipid metabolism, accelerating the development of obesity when individuals are challenged by a second metabolic stressor, such as an obesogenic diet. [ABSTRACT FROM AUTHOR]

Rapidly advancing evidence documents that a broad array of synthetic chemicals found ubiquitously in the environment contribute to disease and disability across the lifespan. Although the early literature focused on early life exposures, endocrine‐disrupting chemicals (EDCs) are now understood to contribute substantially to chronic disease in adulthood, especially metabolic, cardiovascular, and reproductive consequences as well as endocrine cancers. The contribution to mortality is substantial, with over 90,000 deaths annually and at least $39 billion/year in lost economic productivity in the United States (US) due to exposure to certain phthalates that are used as plasticizers in food packaging. Importantly, exposures are disproportionately high in low‐income and minoritized populations, driving disparities in these conditions. Though non‐Hispanic Blacks and Mexican Americans comprise 12.6% and 13.5% of the US population, they bear 16.5% and 14.6% of the disease burden due to EDCs, respectively. Many of these exposures can be modified through safe and simple behavioral changes supported by proactive government action to both limit known hazardous exposures and to proactively screen new industrial chemicals prior to their use. Routine healthcare maintenance should include guidance to reduce EDC exposures, and a recent report by the Institute of Medicine suggests that testing be conducted, particularly in populations heavily exposed to perfluoroalkyl substances—chemicals used in nonstick coatings as well as oil‐ and water‐resistant clothing. [ABSTRACT FROM AUTHOR]

AbstractContext di-(2-Ethylhexyl) phthalate (DEHP) has potential reproductive toxicity. Bu-Shen-Tian-Jing formulations (BSTJFs) are beneficial for female reproductive capacity. However, BSTJF2 has much lower cytotoxicity than BSTJF1.Objective To investigate the effects of BSTJFs on ovarian granulosa cells exposed to DEHP and determine the potential molecular mechanisms.Methods and materials Human granulosa-like tumor cell line (KGN) cells were divided into control, DEHP, BSTJF1 and BSTJF2 groups. The DEHP group were given 1 μM DEHP for 24 h. They were then given BSTJF1 at 200 μg/mL or BSTJF2 at 100 μg/mL for 24 h. The control group was treated with the same concentration of DMSO (0.1%). Oxidative stress and mitochondrial function were measured. The mRNA and protein expression levels of HDAC3 and HSP90AA were determined. Integrative network pharmacology analysis of BSTJF2 was also performed.Results DEHP (1 μM) significantly suppressed the proliferation of KGN cells by 17%, significantly increased ROS levels by 28% and MDA levels by 47%, significantly decreased MMP levels by 22% and mtDNA copy by 30%. DEHP significantly increased protein expression of HDAC3 by 21%and HSP90AA by 64%. All these changes were significantly reversed by BSTJFs. Integrative network pharmacology analysis revealed HSP90AA was a key target (degree = 8). Both RGFP966 and BSTJF2 significantly reversed the increased expression of HDAC3 and HSP90AA, attenuated oxidative stress, and mitochondrial damage which were induced by DEHP.Conclusion BSTJFs might have therapeutic potential on oxidative stress and mitochondrial damage through the HDAC3/HSP90AA pathway which encourages further clinical trials.

Polybrominated diphenyl ethers (PBDEs) are a class of flame-retardant organohalogen pollutants that act as endocrine/neuroendocrine disrupting chemicals (EDCs). In humans, exposure to brominated flame retardants (BFR) or other environmentally persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and novel organophosphate flame retardants has been associated with increasing trends of diabetes and metabolic disease. However, the effects of PBDEs on metabolic processes and their associated sex-dependent features are poorly understood. The metabolic-disrupting effects of perinatal exposure to industrial penta-PBDE mixture, DE-71, on male and female progeny of C57BL/6N mouse dams were examined in adulthood. Dams were exposed to environmentally relevant doses of PBDEs daily for 10 weeks (p.o.): 0.1 (L-DE-71) and 0.4 mg/kg/d (H-DE-71) and offspring parameters were compared to corn oil vehicle controls (VEH/CON). The following lipid metabolism indices were measured: plasma cholesterol, triglycerides, adiponectin, leptin, and liver lipids. L-DE-71 female offspring were particularly affected, showing hypercholesterolemia, elevated liver lipids and fasting plasma leptin as compared to same-sex VEH/CON, while L- and H-DE-71 male F1 only showed reduced plasma adiponectin. Using the quantitative Folch method, we found that mean liver lipid content was significantly elevated in L-DE-71 female offspring compared to controls. Oil Red O staining revealed fatty liver in female offspring and dams. General measures of adiposity, body weight, white and brown adipose tissue (BAT), and lean and fat mass were weighed or measured using EchoMRI. DE-71 did not produce abnormal adiposity, but decreased BAT depots in L-DE-71 females and males relative to same-sex VEH/CON. To begin to address potential central mechanisms of deregulated lipid metabolism, we used RT-qPCR to quantitate expression of hypothalamic genes in energy-regulating circuits that control lipid homeostasis. Both doses of DE-71 sex-dependently downregulated hypothalamic expression of Lepr, Stat3, Mc4r, Agrp, Gshr in female offspring while H-DE-71 downregulated Npy in exposed females relative to VEH/CON. In contrast, exposed male offspring displayed upregulated Stat3 and Mc4r. Intestinal barrier integrity was measured using FITC-dextran since it can lead to systemic inflammation that leads to liver damage and metabolic disease, but was not affected by DE-71 exposure. These findings indicate that maternal transfer of PBDEs disproportionately endangers female offspring to lipid metabolic reprogramming that may exaggerate risk for adult metabolic disease.

Introduction: Although previous studies investigated the potential adverse effects of endocrine-disrupting chemicals (EDCs) on biological age acceleration and aging-related diseases, the mixed effect of multiple types of EDCs on biological age acceleration, including its potential underlying mechanism, remains unclear. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) were used to analyze biological age measures, including Klemera-Doubal method biological age (KDM-BA), phenotypic age, and homeostatic dysregulation (HD). Weight quantile sum (WQS) regression was performed to screen biological age-related EDCs (BA-EDCs) and assess the mixed effect of BA-EDCs on biological age acceleration and aging-related disease. Targets of BA-EDCs were obtained from three databases, while heart aging-related genes were obtained from the Aging Anno database. Protein–protein interaction (PPI) network and MCODE algorithm were applied to identify potential interactions between BA-EDC targets and heart aging-related genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify related pathways. Results: This cross-sectional study included 1,439 participants. A decile increase in BA-EDCs co-exposure was associated with 0.31 years and 0.17 years of KDM-BA and phenotypic age acceleration, respectively. The mixed effect of BA-EDCs was associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD). Vitamins C and E demonstrated a significant interaction effect on the association between BA-EDCs and KDM-BA acceleration. PPI network and functional enrichment analysis indicated that the AGE-RAGE signaling pathway in diabetic complications was significantly enriched. Conclusion: Our results showed that the co-exposure effect of BA-EDCs was associated with biological age acceleration and ASCVD, with the AGE-RAGE signaling pathway being the underlying mechanism. Vitamins C and E may also be an actionable target for preventing EDC-induced biological aging.

di-(2-Ethylhexyl) phthalate (DEHP) has potential reproductive toxicity. Bu-Shen-Tian-Jing formulations (BSTJFs) are beneficial for female reproductive capacity. However, BSTJF2 has much lower cytotoxicity than BSTJF1. To investigate the effects of BSTJFs on ovarian granulosa cells exposed to DEHP and determine the potential molecular mechanisms. Human granulosa-like tumor cell line (KGN) cells were divided into control, DEHP, BSTJF1 and BSTJF2 groups. The DEHP group were given 1 μM DEHP for 24 h. They were then given BSTJF1 at 200 μg/mL or BSTJF2 at 100 μg/mL for 24 h. The control group was treated with the same concentration of DMSO (0.1%). Oxidative stress and mitochondrial function were measured. The mRNA and protein expression levels of HDAC3 and HSP90AA were determined. Integrative network pharmacology analysis of BSTJF2 was also performed. DEHP (1 μM) significantly suppressed the proliferation of KGN cells by 17%, significantly increased ROS levels by 28% and MDA levels by 47%, significantly decreased MMP levels by 22% and mtDNA copy by 30%. DEHP significantly increased protein expression of HDAC3 by 21%and HSP90AA by 64%. All these changes were significantly reversed by BSTJFs. Integrative network pharmacology analysis revealed HSP90AA was a key target (degree = 8). Both RGFP966 and BSTJF2 significantly reversed the increased expression of HDAC3 and HSP90AA, attenuated oxidative stress, and mitochondrial damage which were induced by DEHP. BSTJFs might have therapeutic potential on oxidative stress and mitochondrial damage through the HDAC3/HSP90AA pathway which encourages further clinical trials. [ABSTRACT FROM AUTHOR]

Diabetes, a persistent pathological condition characterized by disruptions in insulin hormone regulation, has exhibited a noteworthy escalation in its prevalence over recent decades. The surge in incidence is notably associated with the proliferation of endocrine-disrupting chemicals (EDCs), which have emerged as primary contributors to the manifestation of insulin resistance and the consequent disruption of beta cell function, ultimately culminating in the onset of diabetes. Consequently, this study endeavors to introduce a model for diabetes that aims to elucidate the ramifications of exposure to EDCs within the diabetic population. In the pursuit of mitigating the deleterious effects of EDC-induced diabetes, we propose a framework for optimal control strategies. The utilization of Pontryagin's maximum principle serves to explicate the principles governing the optimal control mechanisms within the proposed model. Our findings underscore that heightened concentrations of EDCs play a pivotal role in exacerbating the prevalence of diabetes. To substantiate our model, we employ parameter estimation techniques utilizing a diabetes dataset specific to the demographic context of India. This research contributes valuable insights into the imperative need for proactive measures to regulate and diminish EDC exposure, thereby mitigating the escalating diabetes epidemic. [ABSTRACT FROM AUTHOR]

Obesity is now a worldwide pandemic. The usual explanation given for the prevalence of obesity is that it results from consumption of a calorie dense diet coupled with physical inactivity. However, this model inadequately explains rising obesity in adults and in children over the past few decades, indicating that other factors must be important contributors. An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture that interferes with any aspect of hormone action. EDCs have become pervasive in our environment, allowing humans to be exposed daily through ingestion, inhalation, and direct dermal contact. Exposure to EDCs has been causally linked with obesity in model organisms and associated with obesity occurrence in humans. Obesogens promote adipogenesis and obesity, in vivo, by a variety of mechanisms. The environmental obesogen model holds that exposure to obesogens elicits a predisposition to obesity and that such exposures may be an important yet overlooked factor in the obesity pandemic. Effects produced by EDCs and obesogen exposure may be passed to subsequent, unexposed generations. This "generational toxicology" is not currently factored into risk assessment by regulators but may be another important factor in the obesity pandemic as well as in the worldwide increases in the incidence of noncommunicable diseases that plague populations everywhere. This review addresses the current evidence on how obesogens affect body mass, discusses long-known chemicals that have been more recently identified as obesogens, and how the accumulated knowledge can help identify EDCs hazards.

Bisphenol A (BPA) is an endocrine-disrupting chemical with a potential role in endocrine cancers. However, the effects of BPA on the salivary glands have been barely explored. We investigated the impact of in vivo sub-chronic exposure to BPA and its in vitro effects on human salivary gland mucoepidermoid carcinoma cell lines. Male and female mice were exposed to BPA (30 mg/kg/day). Sublingual and submandibular salivary glands from an estrogen-deficiency model were also analyzed. BPA concentration in salivary glands was evaluated by gas chromatography coupled to ion trap mass spectrometry. Immunohistochemical analysis using anti-p63 and anti-α-SMA antibodies was performed on mouse salivary gland tissues. Gene expression of estrogen receptors alpha and beta, P63 and α-SMA was quantified in mouse salivary gland and/or mucoepidermoid (UM-HMC-1 and UM-HMC-3A) cell lines. Cell viability, p63 and Ki-67 immunostaining were evaluated in vitro. BPA disrupted the tissue architecture of the submandibular and sublingual glands, particularly in female mice, and increased the expression of estrogen receptors and p63, effects that were accompanied by significant BPA accumulation in these tissues. Conversely, ovariectomy slightly impacted BPA-induced morphological changes. In vitro, BPA did not affect the proliferation of neoplastic cells, but augmented the expression of p63 and estrogen receptors. The present data highlight a potential harmful effect of BPA on salivary gland tissues, particularly in female mice, and salivary gland tumor cells. Our findings suggest that estrogen-dependent pathways may orchestrate the effects of BPA in salivary glands.

Exposure to endocrine-disrupting chemicals (EDCs) can promote infant neurodevelopmental impairment and maternal postpartum depression (PPD). However, the associations between lactation exposure to EDCs, maternal PPD, and infant neurodevelopment are unclear. Hence, we investigated these relationships in infants aged 36–42 months. We recruited 221 Korean mothers and analyzed 29 EDCs. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess maternal PPD. Bayley scales of infant development; the Swanson, Nolan, and Pelham rating scale (SNAP); and the Child Behavior Checklist (CBCL) were used to assess neurodevelopment in infants exposed to the top 30% of EDC over three years. Multiple regression analyses were adjusted for maternal age, pre-pregnancy body mass index, education, income, employment, residence, and infant age and sex. The rates of infants with clinically abnormal diagnoses on neurologic developmental tests (Balyey, SNAP, and CBCL scales) ranged from 7.7 to 38.5% in this study, with the motor and hyperactivity/impulsivity areas scoring the highest among 65 boys and girls. Mono-2-ethylhexyl phthalate (MEHP) and mono-isononyl phthalate (MiNP) levels in breast milk significantly correlated with infant inattention and hyperactivity. Perfluorononanoic acid (PFNA) and perfluorooctyl sulfonate (PFOS) levels correlated significantly with motor development of BSID-III and total CBCL score which mean infant might have lower developmental status. EDC concentrations in breast milk were not associated with maternal PPD. Overall, lactational exposure to EDCs during the postpartum period can exert a negative effect on maternal PPD and infant neurodevelopment. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is an environmental contaminant present on all continents, including Antarctica, with a potent biocidal action. Its use began to be intensified during the 1960s. It was effectively banned in 2003 but remains in the environment to this day due to several factors that increase its half-life and its misuse despite the bans. In addition to the endocrine-disrupting effect of TBT, which may lead to imposex induction in some invertebrate species, there are several studies that demonstrate that TBT also has an immunotoxic effect. The immunotoxic effects that have been observed experimentally in vertebrates using in vitro and in vivo models involve different mechanisms; mainly, there are alterations in the expression and/or secretion of cytokines. In this review, we summarize and update the literature on the impacts of TBT on the immune system, and we discuss issues that still need to be explored to fill the knowledge gaps regarding the impact of this endocrine-disrupting chemical on immune system homeostasis. [ABSTRACT FROM AUTHOR]

Highlights Prenatal BPA exposure altered the transcriptome profiles of genes associated with ASD in the offspring hippocampus through several ASD-related transcription factors, including AR and ESR1, in a sex-dependent manner. In addition to the known BPA targets (i.e., AR and ESR1), other ASD-related transcription factors, including KDM5B, SMAD4, and TCF7L2, are also involved in the BPA effects in the offspring hippocampus, possibly by direct interactions with BPA. Prenatal BPA exposure also caused a significant reduction in the expression of ASD-related TFs in the hippocampus of female offspring but not in that of males. ASD candidate genes (i.e., AUTS2, SMARCC2, and KMT2C), which are known AR targets, were differentially expressed in response to BPA in the human neuronal cell line with AR overexpression compared to the cell line with low AR protein levels, indicating that AR is involved in BPA-mediated effects on these ASD candidate genes. BPA-responsive genes that are transcriptional targets of AR and other ASD-related transcription factors are associated with synaptogenesis. Prenatal BPA exposure caused an increase in synaptic protein levels in primary hippocampal neurons and in hippocampal tissues of male offspring but not in females.

2,2‐Bis(4‐hydroxyphenyl)propane (bisphenol A; BPA) is an environmental endocrine‐disrupting chemical. It mimics the effects of estrogen at multiple levels by activating estrogen receptors (ERs); however, BPA also affects the proliferation of human breast cancer cells independent of ERs. Although BPA inhibits progesterone (P4) signaling, the toxicological significance of its effects remain unknown. Tripartite motif‐containing 22 (TRIM22) has been identified as a P4‐responsive and apoptosis‐related gene. Nevertheless, it has not yet been established whether exogenous chemicals change TRIM22 gene levels. Therefore, the present study investigated the effects of BPA on P4 signaling and TRIM22 and TP53 expression in human breast carcinoma MCF‐7 cells. In MCF‐7 cells incubated with various concentrations of P4, TRIM22 messenger RNA (mRNA) levels increased in a dose‐dependent manner. P4 induced apoptosis and decreased viability in MCF‐7 cells. The knockdown of TRIM22 abolished P4‐induced decreases in cell viability and P4‐induced apoptosis. P4 increased TP53 mRNA expression and p53 knockdown decrease the basal level of TRIM22 and P4 increased TRIM22 mRNA expression independent of p53 expression. BPA attenuated P4‐induced increases in the ratio of cell apoptosis in a concentration‐dependent manner, and the P4‐induced decreases in cell viability was abolished in the presence of 100 nM and higher BPA concentrations. Furthermore, BPA inhibited P4‐induced TRIM22 and TP53 expression. In conclusion, BPA inhibited P4‐induced apoptosis in MCF‐7 cells via the inhibition of P4 receptor transactivation. TRIM22 gene has potential as a biomarker for investigating the disruption of P4 signaling by chemicals. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the efficacy of modified brick residues for the removal of well-known endocrine disrupting, 4-nonyl phenol (NP) and bisphenol A (BPA) from water. A better comprehension of the in-batch adsorption process was obtained by studying the effect of pH and temperature. The maximum of adsorption capacity was found at neutral pH. The adsorption kinetics, thermodynamics and isotherms modeling for NP and BPA were also investigated. The adsorption process followed Freundlich-type and pseudo-second-order kinetic (R2 > 0.99) with the adsorption capacity 94 and 92 mg/g, respectively, for NP and BPA which was among the highest values of BPA adsorption compared with other carbonaceous adsorbents according to the literature. The thermodynamic studies revealed that the adsorption process was fast and endothermic. The study of the adsorption performance in five consecutive cycles showed efficiencies higher than 90% in all cycles, revealing that the modified brick has good reusability. The results show that the modified brick residues as effective and efficient adsorbent material for the removal of NP and BPA from the water. [ABSTRACT FROM AUTHOR]

Background and Objectives: Fetal growth abnormalities increase the risk of negative perinatal and long-term outcomes. Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical to which humans may be exposed in a number of ways, such as from the environment, via various consumer products, and through the individual's diet. Since the compound possesses estrogen-mimicking properties and exerts epigenetic and genotoxic effects, it has been associated with harmful effects impacting the entire spectrum of human life, including, vitally, the intrauterine period. We investigated the role of maternal exposure to BPA in abnormal fetal growth velocity, both impaired and excessive. Materials and Methods: Amniotic fluid samples were collected from 35 women who underwent amniocentesis early in the second trimester due to medical reasons. Pregnancies were followed until delivery, and birth weights were recorded. The amniotic fluid samples were subsequently divided into three groups based on fetal birth weight, as follows: AGA (appropriate for gestational age), SGA (small for gestational age), and LGA (large for gestational age). Amniotic fluid BPA levels were determined by gas chromatography coupled with mass spectrometry. Results: BPA was detected in 80% (28/35) of our amniotic fluid samples. Median concentration was 281.495 pg/mL and ranged from 108.82 pg/mL to 1605.36 pg/mL. No significant association was observed between the study groups regarding BPA concentration. A significant positive correlation between amniotic fluid BPA concentration and birth weight centile (r = 0.351, p-value = 0.039) was identified. BPA levels were also inversely associated with gestational age in pregnancies at term (between 37 and 41 weeks) (r = −0.365, p-value = 0.031). Conclusions: Our findings suggest that maternal exposure to BPA during the early second trimester of pregnancy can potentially contribute to increased birthweight percentiles and to decreased gestational age in pregnancies at term. [ABSTRACT FROM AUTHOR]

Objective: To examine and further characterize the association between urinary levels of triclosan (TCS), a ubiquitous putative endocrine-disrupting chemical, and the risk of infertility. Design: A retrospective cross-sectional study using the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey. Setting: Not applicable. Patient(s): Female participants in the United States who completed the reproductive health questionnaire and provided urine samples for TCS level measurement from 2013 to 2016. Intervention(s): None. Main Outcome Measure(s): Rates of presumed infertility based on participants’ affirmative response to survey question RHQ074 (“Have you ever attempted to become pregnant over a period of at least a year without becoming pregnant?”). Result(s): A total of 11.7% of the overall female and 12.5% of the eligible study population met the criterion for presumed infertility. Creatinine-adjusted urinary TCS levels were significantly higher among those meeting the criterion for infertility compared with the levels among those who did not. On multivariable-adjusted analyses, individuals with undetectable levels of urinary TCS were 35% less likely to meet the specified infertility criterion compared with those with detectable TCS levels. The magnitude of association between TCS levels and infertility was strongest when comparing the lowest and highest quartiles. The directionality and magnitude of the relationship between TCS levels and infertility were maintained on age-restricted and weighted analyses; however, the associations did not retain statistical significance. Conclusion(s): In a nationally representative sample of women in the United States, an association between TCS exposure and inability to conceive over a period of 1 year is suggested by our analysis of the National Health and Nutrition Examination Survey data. The data infer a dose-response relationship.

Prenatal exposure to metabolism-disrupting chemicals (MDCs) has been linked to birth weight, but the molecular mechanisms remain largely unknown. In this study, we investigated gene expressions and biological pathways underlying the associations between MDCs and birth weight, using microarray transcriptomics, in a Belgian birth cohort. Whole cord blood measurements of dichlorodiphenyldichloroethylene (p,p'-DDE), polychlorinated biphenyls 153 (PCB-153), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and transcriptome profiling were conducted in 192 mother–child pairs. A workflow including a transcriptome-wide association study, pathway enrichment analysis with a meet-in-the-middle approach, and mediation analysis was performed to characterize the biological pathways and intermediate gene expressions of the MDC–birth weight relationship. Among 26,170 transcriptomic features, we successfully annotated five overlapping metabolism-related gene expressions associated with both an MDC and birth weight, comprising BCAT2, IVD, SLC25a16, HAS3, and MBOAT2. We found 11 overlapping pathways, and they are mostly related to genetic information processing. We found no evidence of any significant mediating effect. In conclusion, this exploratory study provides insights into transcriptome perturbations that may be involved in MDC-induced altered birth weight. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an endocrine disruptor that is present in freshwater and marine environments. However, conclusive evidence for the toxicity of chronic BPA exposure to marine fishes remains lacking. Therefore, we investigated the influence of BPA on male marine medaka (Oryzias melastigma). BPA exposure induced formation of testis-ova at 2610 µg/L, and male-type anal fins became more female type in a concentration-dependent manner. Some males with female-type anal fins had normal testes, indicating that anal fin shape is more sensitive to BPA. Gonadal soma-derived factor (gsdf) expression decreased after BPA exposure in the 746 and 2610 µg/L exposure groups, although the changes were not statistically significant. Additionally, liver vitellogenin (vtg) expression increased in a dose-dependent manner and was significantly higher in all exposure groups. vtg and gsdf are likely to be useful biomarkers for the impact of estrogenic endocrine disrupters in O. melastigma. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A (BPA) has been linked to susceptibility to autism spectrum disorder (ASD). Our recent studies have shown that prenatal BPA exposure disrupted ASD-related gene expression in the hippocampus, neurological functions, and behaviors associated with ASD in a sex-specific pattern. However, the molecular mechanisms underlying the effects of BPA are still unclear. Methods: Transcriptome data mining and molecular docking analyses were performed to identify ASD-related transcription factors (TFs) and their target genes underlying the sex-specific effects of prenatal BPA exposure. Gene ontology analysis was conducted to predict biological functions associated with these genes. The expression levels of ASD-related TFs and targets in the hippocampus of rat pups prenatally exposed to BPA were measured using qRT-PCR analysis. The role of the androgen receptor (AR) in BPA-mediated regulation of ASD candidate genes was investigated using a human neuronal cell line stably transfected with AR-expression or control plasmid. Synaptogenesis, which is a function associated with genes transcriptionally regulated by ASD-related TFs, was assessed using primary hippocampal neurons isolated from male and female rat pups prenatally exposed to BPA. Results: We found that there was a sex difference in ASD-related TFs underlying the effects of prenatal BPA exposure on the transcriptome profiles of the offspring hippocampus. In addition to the known BPA targets AR and ESR1, BPA could directly interact with novel targets (i.e., KDM5B, SMAD4, and TCF7L2). The targets of these TFs were also associated with ASD. Prenatal BPA exposure disrupted the expression of ASD-related TFs and targets in the offspring hippocampus in a sex-dependent manner. Moreover, AR was involved in the BPA-mediated dysregulation of AUTS2, KMT2C, and SMARCC2. Prenatal BPA exposure altered synaptogenesis by increasing synaptic protein levels in males but not in females, but the number of excitatory synapses was increased in female primary neurons only. Conclusions: Our findings suggest that AR and other ASD-related TFs are involved in sex differences in the effects of prenatal BPA exposure on transcriptome profiles and synaptogenesis in the offspring hippocampus. These TFs may play an essential role in an increased ASD susceptibility associated with endocrine-disrupting chemicals, particularly BPA, and the male bias of ASD. Highlights: Prenatal BPA exposure altered the transcriptome profiles of genes associated with ASD in the offspring hippocampus through several ASD-related transcription factors, including AR and ESR1, in a sex-dependent manner. In addition to the known BPA targets (i.e., AR and ESR1), other ASD-related transcription factors, including KDM5B, SMAD4, and TCF7L2, are also involved in the BPA effects in the offspring hippocampus, possibly by direct interactions with BPA. Prenatal BPA exposure also caused a significant reduction in the expression of ASD-related TFs in the hippocampus of female offspring but not in that of males. ASD candidate genes (i.e., AUTS2, SMARCC2, and KMT2C), which are known AR targets, were differentially expressed in response to BPA in the human neuronal cell line with AR overexpression compared to the cell line with low AR protein levels, indicating that AR is involved in BPA-mediated effects on these ASD candidate genes. BPA-responsive genes that are transcriptional targets of AR and other ASD-related transcription factors are associated with synaptogenesis. Prenatal BPA exposure caused an increase in synaptic protein levels in primary hippocampal neurons and in hippocampal tissues of male offspring but not in females. [ABSTRACT FROM AUTHOR]

Abstract Objective To conduct a comprehensive systematic review and meta-analysis to estimate the relationship between endocrine-disrupting chemicals (EDCs), including polychlorinated biphenyls (PCBs), poly-brominated diphenyl ethers (PBDEs), phthalates (PAEs), and per- and polyfluoroalkyl substances (PFAS) exposure and risk of gestational diabetes mellitus (GDM). Methods Relevant studies from their inception to November 2021 were identified by searching EMBASE, PubMed, and Web of Science. The cohort and case–control studies that reported effect size with 95% confidence intervals (CIs) of EDC exposure and GDM were selected. The heterogeneity among the included studies was quantified by I 2 statistic. Publication bias was evaluated through the Begg and Egger tests. Results Twenty-five articles with a total of 23,796 participants were found. Results indicated that exposure to PCBs has a significant influence on the incidence of GDM (OR = 1.14; 95% CI = 1.00-–1.31; n = 8). The risk of GDM was found to be associated with PBDE exposure (OR = 1.32; 95% CI = 1.15–1.53; n = 4). PAEs and PFASs exposure were also positively associated with the risk of GDM, with summary ORs of 1.10 (95% CI = 1.03–1.16; n = 7 for PAEs) and 1.09 (95% CI = 1.02–1.16; n = 11 for PFASs), respectively. When only cohort studies were considered, the summary OR between PCBs exposure and the risk of GDM was 0.99 (95% CI = 0.91–1.09; n = 5). Meanwhile, the summary ORs from cohort studies for PBDEs, PAEs, and PFASs exposure were 1.12 (95% CI = 1.00–1.26; n = 2), 1.08 (95% CI = 1.02–1.15; n = 5), and 1.06 (95% CI = 1.00–1.12; n = 8), respectively. The Beggs and Egger tests did not show publication bias, and the sensitivity analyses did not change the results in this meta-analysis. Conclusion These results support that exposure to certain EDCs, including PCBs, PBDEs, PAEs, and PFAS, increase the risk of GDM. Further large-sample epidemiologic researches and mechanistic studies are needed to verify the potential relationship and biological mechanisms. These results are of public health significance because the daily EDC exposure is expected to increase the risk of GDM development. Graphical Abstract

Non-persistent endocrine-disrupting chemicals (EDCs) are of significant concern due to their reproductive toxicity. Previous research reported a relationship between a single type of EDCs and endometriosis. Yet, evidence regarding mixed exposure of multiple categories of EDCs is scarce. Between 2014 and 2018, our hospital-based case-control study recruited 238 endometriosis cases diagnosed by laparoscopy and 296 normal controls in China. Seventeen non-persistent EDCs (phthalates and bisphenols) were measured in urine. The association of single EDC with endometriosis was estimated using logistic regression, while the association between EDC mixture and endometriosis was modeled by Bayesian kernel machine regression (BKMR), quantile-based g-computation (q-gcomp), and principal component analysis (PCA). Consistent results were observed in both single and mixture models where phthalates and bisphenols were associated with increased risk of endometriosis (mixture effect: adjusted odds ratio (aOR)=1.44, 1.22–1.70) and the major contributors were bisphenol A (BPA) and the metabolites of di(2-ethylhexyl) phthalate (DEHP). Interaction analysis showed that bisphenols exhibited significant synergistic interactions with phthalates. Our results suggest that non-persistent EDCs are associated with endometriosis but the underlying mechanisms remain to be elucidated. Our finding may have important public health implications in preventing endometriosis. [Display omitted] • Effects of non-persistent EDCs mixture on endometriosis were investigated. • Seventeen phthalates and bisphenols were measured in women's urine samples. • Phthalates and bisphenols were associated with increased risk of endometriosis. • BPA and the metabolites of DEHP were the major contributors. • Synergistic interactions within phthalates and bisphenols were observed. [ABSTRACT FROM AUTHOR]

Objective: The use of endocrine-disrupting chemicals (EDCs) such as bisphenol A (BPA) in plastics manufacturing, agriculture, livestock, and paint manufacturing increas daily. The water treated in wastewater treatment plants is used in many areas such as irrigation of parks and gardens, and reinforcement of underground water resources. However, whether the treatment process eliminates EDCs in wastewater is not exactly known, and determining this as well as the amounts of these chemicals in treated water are important in terms of protecting the environment and human health. The aim of the study was to determine BPA and phthalate concentrations in the influent and effluent flow samples obtained from wastewater treatment plants. Materials and Methods: BPA and phthalate concentrations were measured in influent and effluent flow samples using the enzymelinked immunosorbent assay (ELISA) method. BPA and phthalate measurements were performed as competitive measurements of BPA and total phthalates in samples using specific monoclonal antibodies. Results: BPA and phthalate levels were measured respectively as 7.69 μg/L and 78.27 μg/L in the influent water samples and 3.17 μg/L and 25.56 μg/L in the effluent water samples. The concentration of BPA and phthalates in the effluent samples decreased significantly compared to the influent water samples. Conclusion: This study is believed to shed light on the importance of monitoring BPA and phthalate concentrations in wastewater treatment plants and inspections for detecting other EDCs in wastewater. [ABSTRACT FROM AUTHOR]

India has achieved its food security through the green revolution and technological revolution, although food safety is still not realized. Subsequently, agricultural runoffs, industrial wastes and domestic sewages continuously contaminate the water and the associated livelihood through several contaminants. Pesticides and their residues, which function as endocrine disrupting chemicals (EDCs), influence the food web through water resources, among other things. The gold standard conventional procedures are used to identify these pesticide residues. However, the introduction of the technology revolution necessitates the use of screening instruments to conduct a pre-inspection of drinkable commodities in order to achieve a better health economy. In the recent decade, microelectronics-based highly sensitive instruments enabled with real-time measurement of pesticide residues is now possible. In addition, the introduction of novel nanosensors and biosensors into revolutionary microelectronics-based devices has improved the performance of these portable instruments in terms of detecting trace-level pesticide residues. Comprehensive assessments of microelectronics-based sensors with comparative benefits, on the other hand, are rare. Herein we review the critical advanced sensory techniques. The significant points are as follows: (1) the state-of-the-art focuses on rapid, portable, and cost-effective optical and electrochemical biosensory tools for pesticide detection in water; (2) a quick overview of commercially available portable devices has been summarized as potential to become next-generation screening tools. [ABSTRACT FROM AUTHOR]

Many industrial chemicals have been reported as antiandrogenic substances. Exposure to these substances represents a potential risk to human health, particularly to the development of reproductive organs such as embryonic external genitalia (eExG). Currently, there is a need for more assay systems that can elucidate the toxicological actions and mechanisms of endocrine-disrupting chemicals. In this study, we show that the eExG slice culture assay is useful for the evaluation of the differing modes of action of endocrine-disrupting chemicals on urethra formation. We assessed the possible endocrine-disrupting activity of 3 chemicals with reported antiandrogenic function, diazinon, dibutyl phthalate, and fenitrothion (FNT) on eExG slices. Exposure to FNT, but not diazinon and dibutyl phthalate, induced defects of androgen-induced urethral masculinization and reduced expression of the androgen-target gene Mafb. Live imaging analyses showed that FNT treatment inhibited androgen-dependent MAFB induction within 12 h. Furthermore, FNT-treated tissue slices showed reduced expression of the androgen receptor. These results indicate that FNT disrupts androgen signaling by reduction of androgen receptor expression during androgen-induced eExG masculinization. This study thus highlights the importance of animal models, which allow for the effective assessment of tissue-specific endocrine-disrupting activity to further reveal the etiology of chemical-induced congenital anomalies. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is an environmental contaminant present on all continents, including Antarctica, with a potent biocidal action. Its use began to be intensified during the 1960s. It was effectively banned in 2003 but remains in the environment to this day due to several factors that increase its half-life and its misuse despite the bans. In addition to the endocrine-disrupting effect of TBT, which may lead to imposex induction in some invertebrate species, there are several studies that demonstrate that TBT also has an immunotoxic effect. The immunotoxic effects that have been observed experimentally in vertebrates using in vitro and in vivo models involve different mechanisms; mainly, there are alterations in the expression and/or secretion of cytokines. In this review, we summarize and update the literature on the impacts of TBT on the immune system, and we discuss issues that still need to be explored to fill the knowledge gaps regarding the impact of this endocrine-disrupting chemical on immune system homeostasis.