The impact of endocrine-disrupting chemicals on stem cells: Mechanisms and implications for human health.

Endocrine-disrupting chemicals (EDCs) are compounds, either natural or man-made, that interfere with the normal functioning of the endocrine system. There is increasing evidence that exposure to EDCs can have profound adverse effects on reproduction, metabolic disorders, neurological alterations, and increased risk of hormone-dependent cancer. Stem cells (SCs) are integral to these pathological processes, and it is therefore crucial to understand how EDCs may influence SC functionality. This review examines the literature on different types of EDCs and their effects on various types of SCs, including embryonic, adult, and cancer SCs. Possible molecular mechanisms through which EDCs may influence the phenotype of SCs are also evaluated. Finally, the possible implications of these effects on human health are discussed. The available literature demonstrates that EDCs can influence the biology of SCs in a variety of ways, including by altering hormonal pathways, DNA damage, epigenetic changes, reactive oxygen species production and alterations in the gene expression patterns. These disruptions may lead to a variety of cell fates and diseases later in adulthood including increased risk of endocrine disorders, obesity, infertility, reproductive abnormalities, and cancer. Therefore, the review emphasizes the importance of raising broader awareness regarding the intricate impact of EDCs on human health.

Identification of endocrine-disrupting chemicals targeting key OP-associated genes via bioinformatics and machine learning.

Osteoporosis (OP), a metabolic disorder predominantly impacting postmenopausal women, has seen considerable progress in diagnosis and treatment over the past few decades. However, the intricate interplay between genetic factors and endocrine disruptors (EDCs) in the pathogenesis of OP remains inadequately elucidated. The objective of this research is to examine the environmental pollutants and their regulatory mechanisms that could potentially influence the pathogenesis of OP, in order to establish a theoretical foundation for the targeted prevention and medical management of individuals with OP. Utilizing CTD and GEO datasets, network toxicology and bioinformatics analyses were conducted to identify target genes from a pool of 98 co-associated genes. Subsequently, a novel prediction model was developed employing a multiple machine learning algorithm. The efficacy of the model was validated based on the area under the receiver operating characteristic curve. Finally, real-time quantitative polymerase chain reaction (qRT-PCR) was used to confirm the expression levels of key genes in clinical samples. We have identified significant genes (FOXO3 and LUM) associated with OP and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, immune infiltration analysis, and molecular docking analysis. Through the analysis of these key genes, we have identified 13 EDCs that have the potential to impact OP. Several endocrine disruptors, such as Dexamethasone, Perfluorononanoic acid, genistein, cadmium, and bisphenol A, have been identified as notable environmental pollutants that impact the OP. Molecular docking analysis revealed significant binding affinity of major EDCs to the post-translational protein structures of key genes. This study demonstrates that EDCs, including dexamethasone, perfluorononanoic acid, genistein, cadmium, and bisphenol A, can be identified as important environmental pollutants affecting OP, and that FOXO3 and LUM have the potential to be diagnostic markers for OP. These results elucidate a novel association between EDCs regulated by key genes and the onset of OP.

The use of in vitro bioassays and chemical screening to assess the impact of a minimally processed vegetable facility on wastewater quality.

Fruit- and vegetable-processing facilities may contaminate wastewater via contaminants found in the produce and disinfecting chemicals used. These contaminants may include agrochemicals, pesticides, and disinfectants such as chlorine and quaternary ammonium compounds (QACs). Some compounds may exhibit harmful endocrine-disrupting activity. This study investigated the impact of a minimally processed vegetable facility on wastewater quality via in vitro bioassays and chemical screening. Estrogen activity was assessed via a yeast estrogen screen (YES), and (anti-)androgenic and glucocorticoid activities were evaluated via an MDA-kb2 reporter gene assay. The samples were screened via gas and liquid chromatography-tandem mass spectrometry (GC-MS/MS and LC-MS/MS) to identify target compounds, and GC coupled with time-of-flight mass spectrometry (GC-TOFMS) was used for non-targeted screening. Sample complexity and chemical profiles were assessed using GC-TOFMS. Estrogenic activity was detected in 16 samples (n = 24) with an upper limit of 595 ± 37 ng/L estradiol equivalents (EEqs). The final wastewater before discharge had an EEq of 0.23 ng/L, which is within the ecological effect-based trigger value range for the estrogenic activity of wastewater (0.2-0.4 ng/L EEq). Androgenic activity was detected in one sample with a dihydrotestosterone equivalent (DHTEq) value of 10 ± 2.7 ng/L. No antiandrogenic activity was detected. The GC-MS/MS and LC-MS/MS results indicated the presence of multiple pesticides, nonylphenols, triclocarban, and triclosan. Many of these compounds exhibit estrogenic activity, which may explain the positive YES assay findings. These findings showed that wastewater from the facility contained detergents, disinfectants, and pesticides and displayed hormonal activity. Food-processing facilities release large volumes of wastewater, which may affect the quality of the water eventually being discharged into the environment. We recommend expanding conventional water quality monitoring efforts to include additional factors like endocrine activity and disinfectant byproducts.

Endocrine disrupting effects on morphological synaptic plasticity.

Neural regulation of the homeostasis depends on healthy synaptic function. Adaptation of synaptic functions to physiological needs manifests in various forms of synaptic plasticity (SP), regulated by the normal hormonal regulatory circuits. During the past several decades, the hormonal regulation of animal and human organisms have become targets of thousands of chemicals that have the potential to act as agonists or antagonists of the endogenous hormones. As the action mechanism of these endocrine disrupting chemicals (EDCs) came into the focus of research, a growing number of studies suggest that one of the regulatory avenues of hormones, the morphological form of SP, may well be a neural mechanism affected by EDCs. The present review discusses known and potential effects of some of the best known EDCs on morphological synaptic plasticity (MSP). We highlight molecular mechanisms altered by EDCs and indicate the growing need for more research in this area of neuroendocrinology.

An in vitro approach reveals molecular mechanisms underlying endocrine disruptor-induced epimutagenesis.

Endocrine disrupting chemicals (EDCs) such as bisphenol S (BPS) are xenobiotic compounds that can disrupt endocrine signaling due to steric similarities to endogenous hormones. EDCs have been shown to induce disruptions in normal epigenetic programming (epimutations) and differentially expressed genes (DEGs) that predispose disease states. Most interestingly, the prevalence of epimutations following exposure to many EDCs persists over multiple generations. Many studies have described direct and prolonged effects of EDC exposure in animal models, but many questions remain about molecular mechanisms by which EDC-induced epimutations are introduced or subsequently propagated, whether there are cell type-specific susceptibilities to the same EDC, and whether this correlates with differential expression of relevant hormone receptors. We exposed cultured pluripotent (iPS), somatic (Sertoli and granulosa), and primordial germ cell-like (PGCLC) cells to BPS and found that differential incidences of BPS-induced epimutations and DEGs correlated with differential expression of relevant hormone receptors inducing epimutations near relevant hormone response elements in somatic and pluripotent, but not germ cell types. Most interestingly, we found that when iPS cells were exposed to BPS and then induced to differentiate into PGCLCs, the prevalence of epimutations and DEGs was largely retained, however, >90% of the specific epimutations and DEGs were replaced by novel epimutations and DEGs. These results suggest a unique mechanism by which an EDC-induced epimutated state may be propagated transgenerationally.

Potential hazards of bisphenol A on the male reproductive system: Induction of programmed cell death in testicular cells.

A common industrial chemical known as bisphenol A (BPA) has been linked to endocrine disruption and can interfere with hormonal signaling pathways in humans and animals. This comprehensive review aims to explore the detrimental consequences of BPA on reproductive organ performance and apoptosis induction, shedding light on the emerging body of evidence from laboratory animal studies. Historically, most studies investigating the connection between BPA and reproductive tissue function have mainly leaned on laboratory animal models. These studies have provided crucial insights into the harmful effects of BPA on several facets of reproduction. This review consolidates an increasing literature that correlates exposure to BPA in the environment with a negative impact on human health. It also integrates findings from laboratory studies conducted on diverse species, collectively bolstering the mounting evidence that environmental BPA exposure can be detrimental to both humans and animals, particularly to reproductive health. Furthermore, this article explores the fundamental processes by which BPA triggers cell death and apoptosis in testicular cells. By elucidating these mechanisms, this review aids a deeper understanding of the complex interactions between BPA and reproductive tissues.

Interactions of Potential Endocrine-Disrupting Chemicals with Whole Human Proteome Predicted by AlphaFold2 Using an In Silico Approach.

Binding with proteins is a critical molecular initiating event through which environmental pollutants exert toxic effects in humans. Previous studies have been limited by the availability of three-dimensional (3D) protein structures and have focused on only a small set of environmental contaminants. Using the highly accurate 3D protein structure predicted by AlphaFold2, this study explored over 60 million interactions obtained through molecular docking between 20,503 human proteins and 1251 potential endocrine-disrupting chemicals. A total of 66,613,773 docking results were obtained, 1.2% of which were considered to be high binding, as their docking scores were lower than -7. Monocyte to macrophage differentiation factor 2 (MMD2) was predicted to interact with the highest number of environmental pollutants (526), with polychlorinated biphenyls and polychlorinated dibenzofurans accounting for a significant proportion. Dimension reduction and clustering analysis revealed distinct protein profiles characterized by high binding affinities for perfluoroalkyl and polyfluoroalkyl substances (PFAS), phthalate-like chemicals, and other pollutants, consistent with their uniquely enriched pathways. Further structural analysis indicated that binding pockets with a high proportion of charged amino acid residues, relatively low α-helix content, and high ß-sheet content were more likely to bind to PFAS than others. This study provides insights into the toxicity pathways of various pollutants impacting human health and offers novel perspectives for the establishment and expansion of adverse outcome pathway-based models.

Astrogenesis in the hypothalamus: A life-long process contributing to the development and plasticity of neuroendocrine networks.

Astrocytes are now recognized as integral components of neural circuits, regulating their maturation, activity and plasticity. Neuroendocrinology has provided fertile ground for revealing the diverse strategies used by astrocytes to regulate the physiological and behavioural outcomes of neural circuit activity in response to internal and environmental inputs. However, the development of astrocytes in the hypothalamus has received much less attention than in other brain regions such as the cerebral cortex and spinal cord. In this review, we synthesize our current knowledge of astrogenesis in the hypothalamus across various life stages. A distinctive feature of hypothalamic astrogenesis is that it persists all throughout lifespan, and involves multiple cellular sources corresponding to radial glial cells during early development, followed by tanycytes, parenchymal progenitors and locally dividing astrocytes. Astrogenesis in the hypothalamus is closely coordinated with the maturation of hypothalamic neurons. This coordination is exemplified by recent findings in neurons producing gonadotropin-releasing hormone, which actively shape their astroglial environment during infancy to integrate functionally into their neural network and facilitate sexual maturation, a process vulnerable to endocrine disruption. While hypothalamic astrogenesis shares common principles with other brain regions, it also exhibits specific features in its dynamics and regulation, both at the inter- and intra-regional levels. These unique properties emphasize the importance of further exploration. Additionally, we discuss the experimental strategies used to assess astrogenesis in the hypothalamus and their potential bias and limitations. Understanding the mechanisms of hypothalamic astrogenesis throughout life will be crucial for comprehending the development and function of the hypothalamus under both physiological and pathological conditions.

Relationship between mixed exposure to phenyl hydroxides, polycyclic aromatic hydrocarbons, and phthalates and the risk of arthritis.

BACKGROUND: To determine the relationship between mixed exposure to three types of endocrine-disrupting chemicals (EDCs), namely phenyl hydroxides, polycyclic aromatic hydrocarbons (PAHs), and phthalates (PAEs), and risk of arthritis. METHODS: Participants were selected from National Health and Nutrition Examination Survey (NHANES). The relationships between the urinary concentrations of phenyl hydroxides, PAHs, and PAEs and the risk of arthritis were analyzed by generalized linear regression model. The mixed exposure to these EDCs and the risk of arthritis was analyzed by weighted quantile sums (WQSs) and Bayesian kernel machine regression (BKMR) model. RESULTS: Our analysis showed that participants with urinary benzophenone-3 and methylparaben concentrations in the highest quartile (Q4) had an increased risk of arthritis compared with those in Q1. For each one-unit increase in the natural logarithm-converted urinary concentrations of 1-hydroxynapthalene and 2-hydroxynapthalene, the risk of arthritis increased by 5% and 8%, respectively. Chemical mixing index coefficients were significantly associated with risk of arthritis in both WQS positive- and negative-constraint models. In the BKMR model, there was a significant positive correlation between mixed exposure and the risk of arthritis. CONCLUSION: Mixed exposure to phenyl hydroxides, PAHs, and PAEs increased the risk of arthritis, with exposure to PAHs being the key factor.

Well-designed chitosan-based cationic porous polymer: A robust material for effective adsorption of endocrine disrupting chemicals.

There is an immediate need for meticulous design of easily accessible, cost-effective, chemically stable and eco-friendly materials for effectively removal of water contaminant. Herein, targeting typical water contaminants, endocrine disrupting chemicals (EDCs), three cationic hyper-cross-linked porous polymers (ciHCP-1, ciHCP-2, ciHCP-3) with multiple adsorption sites were designed with 2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) as precursor. The ciHCP-3 with large surface area (806 m2 g-1) exhibited high sorption capacity (137-366 mg g-1), and fast adsorption kinetics (5 min) for the EDCs, which is superior to the reported sorbents. The adsorption mechanisms can be attributed to the synergistic effect of physisorption and chemisorption. The high preparation reproducibility, physicochemical stability, and reuse capability of ciHCP highlights its great potential in practical water remediation applications.

Developing water quality and land use surrogates to predict endocrine-disrupting chemical profiles in a highly urbanized river basin.

This study investigated geospatial distributions of endocrine-disrupting chemicals (EDCs) in the waters of the Dongjiang River and their associations with anthropogenic activities. Fifteen EDCs, with total concentrations in the river water of 149-2525 ng/L were detected, with bisphenol-A, 4-nonylphenol, 4-tert-octylphenol, p-hydroxybenzoic acid, and methylparaben being the five predominant EDCs. The total estrogen concentration was high downstream and significantly correlated with the spatial distribution of urban land use, wastewater discharge, population, and gross domestic product, indicating human activities have increased estrogen levels and threatened ecological health. The total risk quotient indicated a high ecological risk of estrogens to fish and a moderate to high ecological risk of personal care products to algae. Estrone, triclosan, bisphenol-A, 4-nonylphenol, and 4-tert-octylphenol were categorized as priority pollutants, which required special concern. Triclosan and triclocarban can serve as reliable chemical indicators for predicting EDC levels based on correlation analysis. The crucial factors affecting EDC levels were identified through the Mantel test and predictor importance was quantified using a multiple regression model, which can help predict occurrences and geospatial distributions of EDCs. Total phosphorus and electrical conductivity were the major predictors of EDC levels, providing promising indicators for monitoring EDCs in river water. Urban land proportion significantly affected phenolic environmental estrogens, natural estrogens, and disinfectants. In the main stream, urban population, urbanization rate, and gross domestic product influenced phenolic environmental estrogen levels. A mini-review of the global distribution of EDCs in river water revealed that income and population differences among countries affect their occurrence, suggesting socioeconomic factors should be considered to mitigate EDC pollution.

Effects of exposure to 17α-methyltestosterone on hepatic lipid metabolism in Gobiocypris rarus.

This study aimed to investigate the effects of 17α-Methyltestosterone (MT) on hepatic lipid metabolism in Gobiocypris rarus. G. rarus was exposed to varying concentrations of MT (0, 25, 50, and 100 ng/L) for durations of 7, 14, and 21 d. Biochemical and transcriptomic analyses were conducted using methods, such as ELISA, RT-qPCR, Western Blotting, and RNA-seq, to decipher the key signals and molecular mechanisms triggered by MT in vivo. The results revealed that MT induced hepatomegaly in G. rarus and markedly increased the hepatic steatosis index (HSI). After 14 d of exposure, significant increase in PPARγ mRNA expression was observed, whereas after 21 d, PPARα mRNA expression was significantly reduced. The expression pattern of SREBP1C mRNA initially decreased before increasing, mirroring the trend observed for SREBP1C protein expression. Furthermore, MT increased the levels of key lipid synthesis enzymes, including HSL, CPT1, GPAT, and FAS, thereby fostering lipid accumulation. RNA-seq analysis revealed that MT modulated hepatic bile acid metabolism via the PPAR pathway, consequently influencing cholesterol and lipid metabolism. Considering the differential metabolic pathways of MT across genders, it is postulated that MT may undergo aromatization to estrogen within G. rarus, thereby exerting estrogenic effects. These findings provide crucial experimental insights into the detrimental effects of MT in aquatic settings, underscoring its implications for safeguarding aquatic organisms and human health.

Micro-injection as a tool to detect the effects of bisphenol A, diethyl phthalate, and 17ß-estradiol on ontogenesis of zebrafish (Danio rerio).

Diethyl phthalate (DEP), bisphenol A (BPA), and external estradiol 17ß-estradiol (E2) all are endocrine disrupting chemicals (EDCs). Our previous study has found that the development of ceratohyal cartilage (CH) in embryos could be disrupted when the maternal generation was exposed with 8.06 µM DEP, 2.86 µM BPA, and 1.11 µM E2. However, it is still unknown how doses of the residual EDCs in eggs cause abnormal CH development in their offspring. Microinjection is used at the 2-cell stage of embryos to mimic the maternal effect and to observe the toxicities of EDCs in embryos. Results shown that the amounts of DEP, BPA, and E2 were 1.3 × 10-6 ng, 4.7 × 10-7 ng, and 1.4 × 10-7 ng, respectively, inducing the CH angles to become bigger than the control. However, related genes to the migratory pathways of neural crest cells (NCCs) were not influenced upon BPA and E2 treatments. Both sox10 and smad3 gene expressions were up-regulated upon DEP treatment. On the other hand, the CH angles were smaller than the control upon 1.3 × 10-5, 9.4 × 10-6, and 1.4 × 10-6 ng of DEP, BPA, and E2 microinjection, respectively. Furthermore, genes related to migratory NCCs were significantly influenced upon 10-5 ng of BPA, and 10-4 ng of DEP treatments on embryos. According to the data, we suggested that 10-5-10-7 ng of EDCs in eggs could disrupt CH development as well as significantly increase the mortality on their embryos. The present study raises concern that the responses were highly sensitive in embryos through maternal effects.

Could environmental exposure and climate change Be a key factor in the rising incidence of early onset colorectal cancer?

The emergence of early onset colorectal cancer (EOCRC) is believed to result from the complex interplay between external environmental factors and internal molecular processes. This review investigates the potential association between environmental exposure to chemicals and climate change and the increased incidence of EOCRC, focusing on their effects on gut microbiota (GM) dynamics. The manuscript explores the birth cohort effect, suggesting that individuals born after 1950 may be at higher risk of developing EOCRC due to cumulative environmental exposures. Furthermore, we also reviewed the impact of environmental pollution, including particulate matter and endocrine disrupting chemicals (EDCs), as well as global warming, on GM disturbance. Environmental exposures have the potential to disrupt GM composition and diversity, leading to dysbiosis, chronic inflammation, and oxidative stress, which are known risk factors associated with EOCRC. Particulate matter can enter the gastrointestinal tract, modifying GM composition and promoting the proliferation of pathogenic bacteria while diminishing beneficial bacteria. Similarly, EDCs, can induce GM alterations and inflammation, further increasing the risk of EOCRC. Additionally, global warming can influence GM through shifts in gut environmental conditions, affecting the host's immune response and potentially increasing EOCRC risk. To summarize, environmental exposure to chemicals and climate change since 1950 has been implicated as contributing factors to the rising incidence of EOCRC. Disruptions in gut microbiota homeostasis play a crucial role in mediating these associations. Consequently, there is a pressing need for enhanced environmental policies aimed at minimizing exposure to pollutants, safeguarding public health, and mitigating the burden of EOCRC.

Interference with Systemic Negative Feedback Regulation as a Potential Mechanism for Nonmonotonic Dose-Responses of Endocrine-Disrupting Chemicals.

Background: Endocrine-disrupting chemicals (EDCs) often exhibit nonmonotonic dose-response (NMDR) relationships, posing significant challenges to health risk assessment and regulations. Several molecular mechanisms operating locally in cells have been proposed, including opposing actions via different receptors, mixed-ligand heterodimer formation, and receptor downregulation. Systemic negative feedback regulation of hormone homeostasis, which is a common feature of many endocrine systems, has also been invoked as a mechanism; however, whether and how exactly such global feedback structure may underpin NMDRs is poorly understood. Objectives: We hypothesize that an EDC may compete with the endogenous hormone for receptors (i) at the central site to interfere with the feedback regulation thus altering the physiological hormone level, and (ii) at the peripheral site to disrupt the hormone action; this dual-action may oppose each other, producing nonmonotonic endocrine effects. The objective here is to explore - through computational modeling - how NMDRs may arise through this potential mechanism and the relevant biological variabilities that enable susceptibility to nonmonotonic effects. Methods: We constructed a dynamical model of a generic hypothalamic-pituitary-endocrine (HPE) axis with negative feedback regulation between a pituitary hormone and a terminal effector hormone (EH). The effects of model parameters, including receptor binding affinities and efficacies, on NMDR were examined for EDC agonists and antagonists. Monte Carlo human population simulations were then conducted to systemically explore biological parameter conditions that engender NMDR. Results: When an EDC interferes sufficiently with the central feedback action of EH, the net endocrine effect at the peripheral target site can be opposite to what is expected of an agonist or antagonist at low concentrations. J/U or Bell-shaped NMDRs arise when the EDC has differential binding affinities and/or efficacies, relative to EH, for the peripheral and central receptors. Quantitative relationships between these biological variabilities and associated distributions were discovered, which can distinguish J/U and Bell-shaped NMDRs from monotonic responses. Conclusions: The ubiquitous negative feedback regulation in endocrine systems can act as a universal mechanism for counterintuitive and nonmonotonic effects of EDCs. Depending on key receptor kinetic and signaling properties of EDCs and endogenous hormones, some individuals may be more susceptible to these complex endocrine effects.

Associations of prenatal maternal urinary concentrations of triclosan and benzophenone-3 with cognition in 7.5-month-old infants.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) have been linked to adverse health outcomes and prenatal exposure is known to impact infant and child development. However, few studies have assessed early developmental consequences of prenatal exposure to two common phenolic compounds, benzophenone-3 (BP-3) and triclosan (TCS). OBJECTIVE: We evaluated the relationship of prenatal exposure to BP-3 and TCS with infant cognition at 7.5 months via performance on a visual recognition memory (VRM) task. METHODS: Drawing from the Illinois Kids Development Study (IKIDS) cohort, prenatal exposure to BP-3 and TCS was assessed in pools of five urine samples collected from each woman across pregnancy. Cognition was measured in 310 infants using a VRM task assessing information processing speed, attention, and recognition memory through infrared eye-tracking. Generalized linear regression estimated exposure-outcome associations, followed by stratification to investigate modification of associations by infant sex and stimulus set. RESULTS: Sampled mothers were more likely to be white, college educated, and middle or high income relative to the US population. Mean chemical exposures were significantly higher than those of adult women in the NHANES cohort. In models adjusted for income, gestational age at birth, and testing age, prenatal BP-3 exposure was associated with an increase in run duration (average time spent looking at the stimuli before looking away) (ß = 0.0011, CI -0.0001:0.0022), indicating slower information processing speed, while TCS was associated with significantly longer time to familiarization (time to accrue a total of 20 s of looking time to the stimuli) (ß = 0.0686, CI 0.0203:0.1168, p < 0.01), indicating poorer attention. Stratum-specific analyses isolated both effects to male infants who viewed the second of two stimulus sets. CONCLUSION: Higher prenatal exposure to triclosan was associated with poorer attention in infancy, while benzophenone-3 may be associated with slower information processing speed, particularly among males.

Effects of maternal nonylphenol exposure on the proliferation of glial cells in the brain of male offspring mice.

Glial cells play a significant role in maintaining brain homeostasis and normal brain development, and their functions can be impaired by exposure to endocrine disruptors. 4-n-Nonylphenol (NP), a representative endocrine disruptor, is widely used in personal care products and industrial materials. NP accumulates in various organs, including the brain, of living organisms and adversely influences brain health. However, studies on the effects of NP on glial cells are limited. This study aims to investigate the effects of NP on glial cells using primary mixed glial cells and offspring mice exposed to NP during gestation and lactation. In vitro experiments revealed that NP exposure stimulated the astrocytes and microglia proliferation but not oligodendrocytes. NP exposure activated microglia and reduced myelin protein expression in oligodendrocytes. Moreover, maternal NP exposure increased the numbers of microglia and oligodendrocytes in the cerebral cortex of adult offspring. NP exposure caused anxiety- and depressive-like behaviors in adult mice. Collectively, these findings suggest that maternal NP exposure negatively affects the brain development in adult offspring mice.

The Association between Maternal Endocrine-Disrupting Chemical Exposure during Pregnancy and the Incidence of Male Urogenital Defects: A Systematic Review and Meta-Analysis.

The increasing incidence of hypospadias and cryptorchidism, coupled with the widespread presence of endocrine-disrupting chemicals (EDCs), has raised concerns about the potential impact of these environmental factors on male urogenital development. This systematic review and meta-analysis aims to evaluate the association between maternal exposure to various EDCs and the risk of hypospadias and cryptorchidism. We conducted a comprehensive search of PubMed, Scopus, Web of Science, and Cochrane databases from inception until May 2024. We included case-control and cohort studies that examined the association between maternal EDC exposure and hypospadias or cryptorchidism, reporting adjusted odds ratios (aOR) or crude odds ratios (cOR). Data were extracted and pooled using a random effects model, and heterogeneity was assessed using the Q test and I-square statistics. The risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS). A total of 48 studies were included in the systematic review, with 46 studies included in the meta-analysis. The pooled analysis revealed a significant association between maternal EDC exposure and an increased risk of hypospadias (aOR = 1.26, 95% CI: 1.18-1.35, p < 0.0001) and cryptorchidism (aOR = 1.37, 95% CI: 1.19-1.57, p < 0.001). Subgroup analyses showed that exposure to pesticides, phthalates, alkyl phenolic compounds (ALKs), and heavy metals significantly increased the risk of hypospadias. In contrast, polychlorinated biphenyls (PCBs) did not show a significant association. Significant associations were found with pesticide and PCB exposure for cryptorchidism, but not with phthalate, ALK, or heavy metal exposure. Maternal exposure to certain EDCs is associated with an increased risk of hypospadias and cryptorchidism in male children. These findings underscore the importance of addressing environmental and occupational exposures during pregnancy to mitigate potential risks. Further research is needed to elucidate the mechanisms by which EDCs affect urogenital development and to develop effective interventions to reduce exposure among vulnerable populations.

Multiplex aptamer cluster detection platform and systems toxicology study for 17ß-estradiol, bisphenol A, and diethylstilbestrol.

Intake of 17ß-estradiol (E2), bisphenol A (BPA), and diethylstilbestrol (DES) from food can contribute to endocrine disorders. Therefore, developing a sensitive method for the simultaneous detection of E2, BPA, and DES and understanding their combined effects on endocrine disruption are crucial. We developed a fluorescence aptasensing platform utilizing DNase I-assisted cyclic enzymatic signal amplification in conjunction with an aptamer/graphene oxide complex. Using PEG 20000 as a surface-blocking agent, the aptasensor achieved ultralow detection limits of 2.643, 0.3039, and 0.6996 for E2, BPA, and DES, respectively. The sensor demonstrated accurate detection in plastic bottled water at spiked levels of 10 and 100 ng/mL. Systems toxicology revealed 30 potential targets for mixture-induced endocrine disruption. Molecular docking showed binding affinities of E2, BPA, and DES for ESR1 of -9.94, -8.29, and - 8.98 kcal/mol, respectively. These results highlight the effectiveness of the aptasensor and provide valuable insights into endocrine disruption mechanisms.

Evaluation of Exposure to Bisphenol A, Bisphenol F, and Phthalates in Patients with Phenylketonuria and Its Differences According to Dietary Status.

BACKGROUND: Phenylketonuria (PKU) is the most common amino acid metabolism disorder. Patients with blood phenylalanine (Phe) levels of ≥6 mg/dL require treatment, and the most definitive treatment is the Phe-restricted diet. Bisphenols and phthalates are widely used endocrine-disrupting chemicals (EDCs) found in personal care products, baby bottles, and food packaging. METHODS: In this study, we evaluated the possible routes of exposure to these EDCs in patients diagnosed with PKU (n = 105, 2-6 years of age) and determined the relationship between the plasma levels of bisphenol A (BPA), bisphenol F (BPF), di-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), mono-(2ethylhexyl) phthalate (MEHP), and dietary regimens. Participant characteristics and exposure routes were evaluated according to their dietary treatment status. RESULTS: Thirty-four of these patients were on a Phe-restricted diet, while the remaining 71 had no dietary restrictions. DBP and DEHP levels were higher in those using plastic tablecloths (p = 0.049 and p = 0.04, respectively). In addition, plasma DBP levels were higher in those who used bottled water (p = 0.01). Being under 4 years of age, using plastic food containers, and using plastic shower curtains were characteristics associated with higher MEHP levels (p = 0.027, p = 0.019, and p = 0.014, respectively). After adjustment for baseline characteristics (Model 1), the odds of having a plasma BPA level in the upper tertile were 3.34 times higher in the free-diet group (95% CI = 1.09-10.25). When we additionally adjusted for plastic exposure (Model 2), the odds ratio was found to be 18.64 (95% CI = 2.09-166.42) for BPA. In the free-diet group, the probability of having plasma DEHP levels in the upper tertile was increased by a relative risk of 3.01 (p = 0.039, 95% CI = 1.06-8.60). CONCLUSION: Our results indicate that exposure to bisphenols and phthalates varies with dietary treatment. The difference in sources of exposure to EDCs between the diet and non-diet groups indicates that diet plays an important role in EDC exposure.