Search Results (119)

Bisphenol A (BPA) is one of the most produced compounds worldwide. It acts as an endocrine disruptor and can cause adverse effects in the body, even at low-dose exposures. By interacting with estrogen receptors, it can play an important role in the pathogenesis of several endocrine diseases, such as infertility, hormone-dependent tumours and various metabolic disorders. Exposure in humans, especially early in life, is of particular concern, since it can have a big impact on an individual’s development and growth. The objective of this study was to evaluate, in vivo, the genotoxicity of BPA and its effects on longevity, prolificacy and behaviour in Drosophila melanogaster. To evaluate the biological and behavioural effects, flies were crossed and subjected to different concentrations of BPA (0.5 mM, 1 mM, 2 mM, 5 mM and 10 mM) in Drosophila instant “Carolina” medium hydrated with the BPA solution for 3 days, and then transferred to a non-treated medium, where they continued to lay eggs. This procedure was repeated to obtain the F₂ generation. To evaluate genotoxicity, the somatic mutation and recombination test (SMART) and Comet assays were performed. In these cases, higher concentrations of BPA were chosen (1 mM, 10 mM, 20 mM and 50 mM). The results showed that this compound caused changes in longevity and prolificacy, and that these changes also affected subsequent generations. They also showed that BPA affected Drosophila’s behaviour and social interaction, but at the exposure levels investigated here, it did not cause significant genotoxic effects. Full article

Bisphenol A (BPA) is the most used widely synthetic compound for the manufacture of polycarbonate plastics and epoxy resins produced worldwide. Given its androgenic and estrogenic activities, BPA is an endocrine disruptor that is linked to neurological and vascular outcomes, including strokes. Therefore, this study aims to investigate the mechanisms by which a 24 h exposure to BPA (0.002–20 μM) modifies the contractile function of rat middle cerebral artery (MCA) smooth muscle cells (SMCs). Thus, MCA explants were isolated from Wistar rats, and the SMC-MCA vasoactive response was assessed using planar cell surface area, while the gene expression of proteins and ion channel subunits involved in the MCA vasoactive response was evaluated by real-time quantitative PCR. The exposure to BPA (0.02 and 2 μM) decreased the noradrenaline (NA) vasocontractile response and sodium nitroprusside (SNP) vasorelaxant response. Moreover, exposure to BPA (0.02 and 2 μM) increased the gene expression of the soluble guanyl cyclase protein and the large conductance Ca²⁺-activated K⁺ channels (1.1 α-subunit). These results suggest an impairment of the SMC-MCA vasoactive response induced by intermediate BPA concentrations, an effect not attained for the lowest or highest exposure concentrations (non-monotonic inverted U-shaped response). In summary, these findings suggest that BPA exposure modifies MCA vascular homeostasis by interfering with the nitric oxide (NO) pathway and may, thus, be involved in ischemic stroke development. Full article

Background/Objectives: Flavonoids are common ubiquitous components of plants and are consumed by humans and livestock in their diets. Many different activities have been proposed for a variety of flavonoids that play a role in the benefits of a plant-rich diet. On the downside, excessive exposure to some flavonoids comes with a risk of endocrine disruption. Our objective was to define the structural elements of flavones and selected other flavonoids required for endocrine-disrupting activities on each of four steroid receptors, estrogen, androgen, progesterone, and glucocorticoid receptors. Methods: This work presents a systematic screen for the hormone agonist or antagonist activity of a selected panel of flavonoids on estrogen, androgen, progesterone, and glucocorticoid receptors. The screen is focused on the positional requirements of hydroxyl substituents on the flavone backbone. Results: Each receptor exhibited a distinct pattern for structural requirements of the flavones to impact receptor signaling. The most active flavones exhibited antagonist activity on androgen and progesterone receptors with an IC₅₀ of 0.5 and 2 µM, respectively. Flavones only exhibited weak antagonism on glucocorticoid receptors. When active, flavones acted as estrogen receptor agonists. The findings were utilized to design and synthesize a novel flavone, 3-fluoro, 6,4′-dihydroxyflavone 14, that displays increased potency as an estrogen agonist (EC₅₀~30 nM). Modeling of the binding of this novel flavone predicts increased preference for ERα versus ERβ relative to the estrogenic phytoestrogen, genistein. Conclusions: The structural requirements for flavones to act as estrogen agonists and antagonists of other steroid receptors are defined. The synthesis of a novel flavone offers potential for topical applications where systemic estrogen activity is undesired. However, the results highlight the potential for endocrine disruption when certain flavones are consumed in quantity as supplements. Full article

Endocrine disruptors (EDs), including natural estrogens, such as 17β-estradiol (E2) and synthetic chemicals (e.g., bisphenol A (BPA) and per- and polyfluoroalkyl substances (PFAS)), pose environmental and human health risks due to their ability to interfere with hormonal systems, even at trace concentrations and can lead to developmental, reproductive, and carcinogenic effects. These persistent compounds often escape removal in conventional wastewater treatment processes, leading to environmental contamination and human exposure. Given their widespread presence in wastewater and resistance to conventional treatments, the use of fungi offers a promising bioremediation strategy. This review explores the potential of fungal biodegradation, particularly using the white-rot fungus Trametes versicolor, in mitigating the estrogenic activity of EDs in wastewater. Laccase, an oxidative enzyme produced by white-rot fungus, shows high efficiency in degrading EDs, positioning fungal treatment as an eco-friendly alternative to conventional technologies. This systematic literature review was conducted using the Methodi Ordinatio, a multi-criteria decision-making methodology that allows for a structured selection of relevant studies and underscores the significant potential of fungal-based systems in addressing the global challenge of ED contamination in water environments. Full article

Phytoestrogens are components naturally occurring in plants and include many foods that are part of the regular diet of animals and humans. Phytoestrogens are xenoestrogens of plant origin that are not produced in the endocrine system. Phytoestrogens can act as either agonists or antagonists, depending on their tissue concentrations and the levels of endogenous estrogens at various life stages. The aim was to evaluate the intake of phytoestrogens and the estrogenic effect of the diet of women at university in Chihuahua (Mexico). In total, 400 female university students individually filled out a food frequency questionnaire (FFQ) that included 120 foods. Estimates of the intake of phytoestrogen (genistein, daidzein, biochanin A, formononetin, matairesinol, coumestrol, enterolactone, secoisoresinol, enterodiol) in the subjects’ daily diet were based on published reports. Quantification of phytoestrogens was expressed in µg day⁻¹. The estrogenic effect of those compound identified according to the foods consumed was estimated using the in vitro E-SCREN test. SPSS v.22.0 (IBM, Chicago, IL, USA) was applied for statistical analysis following descriptive analysis and stepwise regression. p < 0.050 was taken as significant. The results of intake show that the majority of isoflavones are formononetin (median 110.60 (μg day⁻¹) and their estrogenic activity is 4.11 Eq. E2 (pmol day⁻¹); the majority of lignans are enterolactone (median 147.24 (μg day⁻¹), and their estrogenic activity is 4.94 Eq. E2 (pmol day⁻¹). The total phytoestrogen estrogenic effect is measured in pM of E2, with a mean of 28.28 (SD = 23.97) and median of 21.50. The mean consumption of phytoestrogens in Mexican university students is similar to the consumption found in similar studies in the United States, England, Germany, and Spain (<1 mg day⁻¹). Phytoestrogens can be beneficial in adult women during perimenopause and menopause due to their estrogenic effects, but they are less recommended for women in the fertile stage, as, for example, in the study presented here, because they could function as endocrine disruptors. They are not recommended as dietary supplements for young women or pregnant women. Full article

Vascular diseases, such as hypertension, atherosclerosis, cerebrovascular, and peripheral arterial diseases, present major clinical and public health challenges, largely due to their common underlying process: vascular remodeling. This process involves structural alterations in blood vessels, driven by a variety of molecular mechanisms. The inhibitor of DNA-binding/differentiation-3 (ID3), a crucial member of ID family of transcriptional regulators, has been identified as a key player in vascular biology, significantly impacting the progression of these diseases. This review explores the role of ID3 in vascular remodeling, emphasizing its involvement in processes such as apoptosis, cell proliferation, and extracellular matrix regulation. Furthermore, we examine how oxidative stress, intensified by exposure to estrogenic endocrine disruptors (EEDs) like polychlorinated biphenyls (PCBs) and bisphenol A (BPA), affects ID3 activity and contributes to vascular disease. Understanding the interaction between ID3 signaling and EED exposure provides critical insights into the molecular mechanisms underlying vascular remodeling and its role in the development and progression of vascular diseases. Full article

Nowadays, developing countries have seen a reduction in male reproductive parameters, and it has been linked to the exposure of endocrine disrupting chemicals (EDCs), which are able to mimic or disrupt steroid hormone actions. Also, nanoparticles have shown effects on the male reproductive system, in particular the use of TiO₂-NPs in drugs, cosmetics, and food as pigment additives, and, thanks to their small size (1–100 nm), provide themselves the opportunity to be internalized by the body and pass the blood–testis barrier (BTB). Therefore, TiO₂-NPs can act on spermatogenesis and spermatozoa. In this study, we carried out an in vitro assay on human spermatozoa to evaluate the effects of TiO₂-NPs at the concentrations of 500, 250, 100, and 50 ppm. Exposure did not statistically alter sperm parameters (e.g., motility and viability) but induced damage to sperm DNA and the expression of biomarkers by spermatozoa. This immunofluorescence investigation showed a positivity for biomarkers of stress (HSP70 and MTs) on the connecting piece of spermatozoa and also for sex hormone binding globulin (SHBG) biomarkers. The SHBG protein acts as a carrier of androgens and estrogens, regulating their bioavailability; therefore, its expression in the in vitro assay did not rule out the ability of TiO₂-NPs to act as endocrine disruptors. Full article

Estrogens, widely used for therapeutic or contraceptive purposes, act as endocrine disruptors in aquatic systems and have adverse effects on a wide range of living organisms. Wastewater insufficiently treated by conventional methods is the main way for estrogens to enter aquatic systems. Therefore, the purpose of this paper is to develop a novel photocatalytic system for the removal of the estrogenic mixture estradiol valerate/norgestrel from wastewater. The photocatalytic modules are operated in a plug flow reactor system under a UV-A radiation field, and the photocatalyst (TiO₂, ZnO or TiO₂/ZnO) is immobilized on an inert support of glass balls that are strung on stainless-steel wire and arranged in rows along the photocatalytic modules. The photocatalysts were synthesized by the sol–gel method and then deposited on the inert glass support by the hot method, after which it was calcined for two hours at a temperature of 500 °C. The experimental results showed that the efficiency of photocatalytic degradation largely depends on the dose of photocatalyst. The dose of photocatalyst can be adjusted by adding or removing photocatalytic modules, each of which have an approximately equal amount of photocatalyst. The best result was obtained for the TiO₂/ZnO photocatalyst, the organic substrate being practically mineralized in 120 min, for which only two photocatalytic modules are needed. Full article

Background: Breast cancer incidence and mortality exhibit a rising trend globally among both premenopausal and postmenopausal women, suggesting that there are serious errors in our preventive and therapeutic measures. Purpose: Providing a series of valuable, but misunderstood inventions highlighting the role of increasing estrogen signaling in prevention and therapy of breast cancer instead of its inhibition. Results: 1. Breast cells and breast cancer cells with germline BRCA1/2 mutations similarly show defects in liganded estrogen receptor (ER) signaling, demonstrating its role in genomic instability and cancer initiation. 2. In breast tumors, the increased expression of special receptor family maybe an effort for self-directed improvement of genomic defects, while the weakness or loss of receptors indicates a defect requiring medical repair. 3. ER overexpression in breast cancer cells is capable of strengthening estrogen signaling and DNA repair, while in ER negative tumors, HER2 overexpression tries to upregulate unliganded ER activation and genome stabilization. 4. ER-positive breast cancers responsive to endocrine therapy may show a compensatory ER overexpression resulting in a transient tumor response. Breast cancers non-responsive to antiestrogen treatment exhibit HER2-overexpression for compensating the complete inhibition of hormonal ER activation. 5. In breast tumors, somatic mutations serve upregulation of ER activation via liganded or unliganded pathway helping genome stabilization and apoptotic death. 6. The mutual communication between breast cancer and its inflammatory environment is a wonderful partnership among cells fighting for genome stabilization and apoptotic death of tumor. 7. In breast cancers, there is no resistance to genotoxic or immune blocker therapies, but rather, the nonresponsive tumor cells exhaust all compensatory possibilities against therapeutic damages. Conclusions: Understanding the behavior and ambition of breast cancer cells may achieve a turn in therapy via applying supportive care instead of genotoxic measures. Full article

Endometriosis is a chronic gynecological disease, primarily associated with pelvic pain and infertility, that affects approximately 10% of the women of reproductive age. Estrogen plays a central role in endometriosis, and there is growing evidence that endocrine disruptors, such as phthalates, may contribute to its development. This review aimed to determine whether there is a causal relationship between phthalate exposure and the development of endometriosis, as well as the possible effects of phthalates on fertility, by analyzing epidemiological data. After a literature search with a combination of specific terms on this topic, we found that although there are limitations to the current studies, there is a clear association between phthalate exposure and endometriosis. Phthalates can interfere with the cellular processes of the endometrium; specifically, they can bind to PPAR and ER-α and activate TGF-β, promoting different signaling cascades that regulate the expression of specific target genes. This may lead to inflammation, invasion, cytokine alteration, increased oxidative stress, and impaired cell viability and proliferation, culminating in endometriosis. Nevertheless, future research is important to curb the progression and development of endometriosis, and strategies for prevention, diagnosis, and treatment are a priority. In this regard, public policies and recommendations to reduce exposure to phthalates and other endocrine disruptors should be promptly implemented. Full article

Glyphosate, the active ingredient of several broad-spectrum herbicides, is widely used throughout the world, although many adverse effects are known. Among these, it has been recognized as an endocrine disruptor. This work aimed to test the effects and potential endocrine disrupting action of glyphosate on PNT1A human prostate cells, an immortalized non-tumor epithelial cell line, possessing both ERα and ERβ estrogen receptors. The results showed that glyphosate induces cytotoxicity, mitochondrial dysfunction, and rapid activation of ERα and ERβ via nuclear translocation. Molecular analysis indicated a possible involvement of apoptosis in glyphosate-induced cytotoxicology. The apoptotic process could be attributed to alterations in mitochondrial metabolism; therefore, the main parameters of mitochondrial functionality were investigated using the Seahorse analyzer. Impaired mitochondrial function was observed in glyphosate-treated cells, with reductions in ATP production, spare respiratory capacity, and proton leakage, along with increased efficiency of mitochondrial coupling. Finally, the results of immunofluorescence analysis demonstrated that glyphosate acts as an estrogen disruptor determining the nuclear translocation of both ERs. Nuclear translocation occurred independent of dose, faster than the specific hormone, and persisted throughout treatment. In conclusion, the results collected show that in non-tumor prostate cells glyphosate can cause cell death and acts as a xenoestrogen, activating estrogen receptors. The consequent alteration of hormonal functions can have negative effects on the reproductive health of exposed animals, compromising their fertility. Full article

Bisphenol S (BPS), an environmental endocrine disruptor, has been identified in global environmental matrices. Nevertheless, limited studies have investigated the presence of chlorinated analogues of BPS (Clx-BPSs) with potential estrogenic activities in environmental matrices. In this study, the occurrence of BPS and five types of Clx-BPSs was characterized in indoor dust (n = 178) from Hangzhou City. BPS was measurable in 94% of indoor dust samples, with an average level of 0.63 μg/g (<LD–2.4 μg/g). Among the detected Clx-BPSs homologues, Cl₁-BPS (2-chloro-4-(4-hydroxyphenyl)sulfonylphenol; detection frequency 70%), Cl₂-BPS-2 (2-chloro-4-(3-chloro-4-hydroxyphenyl)sulfonylphenol; 65%), and Cl₂-BPS-1 (2,6-dichloro-4-(4-hydroxyphenyl)sulfonylphenol; 61%) were among the frequently detected Clx-BPSs. Cl₁-BPS was the most abundant analyte, with an average of 0.048 μg/g (<LD—0.24 μg/g), followed by Cl₂-BPS-1 (0.035 μg/g, <LD—0.14 μg/g), and Cl₂-BPS-2 (0.031 μg/g, <LD—0.13 μg/g). Significant correlations in indoor dust concentrations were observed between BPS and Cl₁-BPS (p < 0.01), as well as between BPS and Cl₂-BPS-1 (p < 0.01). Moreover, an estimation was made for the total daily intake of Clx-BPSs via the ingestion of indoor dust by infants, children, and adults. This study presents the first evidence of the existence of Clx-BPSs in indoor dust, concurrently highlighting the necessity to address their potential human exposure risks. Full article

Bisphenol-A (BPA), a synthetic compound ubiquitously present in the environment, can act as an endocrine disruptor by binding to both canonical and non-canonical estrogen receptors (ERs). Exposure to BPA has been linked to various cancers, in particular, those arising in hormone-targeted tissues such as the breast. In this study, we evaluated the effect of BPA intake through drinking water on ErbB2/neu-driven cancerogenesis in BALB–neuT mice, transgenic for a mutated ErbB2/neu receptor gene, which reproducibly develop carcinomas in all mammary glands. In this model, BPA accelerated mammary cancerogenesis with an increase in the number of tumors per mouse and a concurrent decrease in tumor-free and overall survival. As assessed by immunohistochemistry, BALB–neuT tumors were ER-negative but expressed high levels of the alternative estrogen receptor GPR30, regardless of BPA exposure. On the other hand, BPA exposure resulted in a marked upregulation of progesterone receptors in preinvasive tumors and of Ki67, CD31, and phosphorylated Akt in invasive tumors. Moreover, based on several infiltration markers of immune cells, BPA favored an immunosuppressive tumor microenvironment. Finally, in vitro cell survival studies performed on a cell line established from a BALB–neuT breast carcinoma confirmed that BPA’s impact on cancer progression can be particularly relevant after chronic, low-dose exposure. Full article

In this study, we present a method for ion-associated liquid phase (IALP) separation and concentration of analytes from an aqueous matrix into an IALP formed in situ by the charge neutralization reaction of organic cations and anions, without centrifugation. The effects of various factors on the extraction efficiency and other parameters are investigated, whereas no instrumental stirring, such as vortexing or ultrasonics, is required because the solvent (IALP) is formed in situ. The organic cation and anion used are ethylhexyloxypropylammonium and dodecyl sulfate, respectively. The developed in situ IALP microextraction method for phase separation without centrifugation is tested using the thymol blue dye and several endocrine disruptors. The tested endocrine disruptors (bisphenol A, 17β-estradiol, 17α-ethinylestradiol, and estrone) are analyzed via high-performance liquid chromatography/fluorescence detection, with respective detection limits of 0.02, 0.02, 0.02, and 0.4 μg L⁻¹, and the corresponding enrichment factor ranging from 47 to 71. This IALP microextraction method can be used to separate and concentrate environmental water samples of different matrices. The employed IALP is fast and easy to use, enables an approximately 100-fold analyte concentration, and has a high affinity for estrogens, thus holding promise for the separation, concentration, and quantitation of diverse trace analytes. Full article

The fast development of China’s urbanization has led to a notable release of emerging pollutants, including microplastics (MPs) and endocrine disruptors (EDCs). Generally, these pollutants enter the coastal environment through the discharge of wastewater treatment plants (WWTPs) and finally threaten the organisms in the receiving waterbody. The study investigated the environmental behavior of MPs and EDCs in two typical WWTPs in one of the megacities in China, Shanghai. The abundance of MPs in the influent ranged from 321 to 976 items/L. Four shapes (films, fragments, fibers, and microbead) were found, while fibers and films dominated. Transparent (31–63%) and white (20–47%) MPs were more frequently observed, while polyethylene terephthalate, cellulose, and cellophane were the main polymetric materials. The size of the MPs fell between 15.8 μm and 2220 μm, and the smaller one (<500 μm) dominated. The removal efficiencies of the two WWTPs for MPs ranged from 64% to 92%, and both WWTPs performed better for large pieces of MPs (>500 μm). For EDCs, total concentrations in the influent were detected, ranging from 113 to 2780 ng/L. Two groups, including phenolic estrogens (PEs) and steroid estrogens (SEs), were detected, and PEs, especially bisphenol A (BPA), were the predominant individuals among the studied EDCs. Specifically, PEs ranged from 82.8 to 2637 ng/L, while SEs ranged from 27.3 to 143 ng/L. The removal efficiencies of the WWTPs for EDCs varied (82.8–100%) as well, possibly due to the different treatment compartments and contamination load in the influent. Seasonal variations for both MPs and EDCs were observed. Specifically, concentrations of MPs and EDCs in WWTPs influent were higher in the wet season, as well as the removal efficiency. Furthermore, there was a correlation observed between the concentrations of MPs and EDCs, suggesting that MPs and EDCs may originate from the same source and that EDCs released by MPs cannot be ignored during treatment. Finally, the study evaluated the environmental risk of the effluents. MPs led to a minor risk (Level I), while EDCs might lead to an adverse impact on algae (RQs = 0.0014–0.024) and fish (RQs = 3.4–30.2). In summary, WWTPs received considerable amounts of MPs and EDCs. Although the WWTPs removed the contaminants efficiently, the environmental risk of the effluent needs to be noted. Full article