Search Results (90)

Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative agents of endometriosis, and highlight implications in the general population and clinical work. A thorough review of experimental, epidemiologic, and mechanistic research studies was conducted to explain the association between EDCs and endometriosis. Among the primary EDCs under investigation are polychlorinated biphenyls, dioxins, phthalates, and bisphenol A (BPA). Despite methodological heterogeneity and some discrepancies, epidemiologic evidence supports a positive association between some increased levels of BPA, phthalates, and dioxins in urine or in blood, and endometriosis. Experiments support some effect of EDCs on endometrial cells and causing endometriosis. EDCs function as xenoestrogens, alter immune function, induce oxidative stress, and disrupt progesterone signaling. Epigenetic reprogramming may play a role in mediating EDC-induced endometriosis. Endocrine, immunological, and epigenetic pathways link EDCs and endometriosis. Prevention techniques require deeper comprehension of those factors. Causal linkages and possible treatment targets should be based on longitudinal studies and multi-omics techniques. Restriction of EDCs could be beneficial for endometriosis prevalence limitation. Full article

Background: Gastric cancer (GC) is a highly heterogeneous disease and remains one of the major causes of cancer-related mortality worldwide. The vast majority of GC cases are adenocarcinomas including diffuse and intestinal GC that may differ in their incidence between Asian and non-Asian cohorts. The intestinal-subtype GC has declined over the past 50 years. In contrast to the intestinal-subtype adenocarcinoma, the incidence of diffuse-subtype GC, often associated with poor overall survival, has constantly increased in the USA and Europe. The aim of this study was to analyze the expression and clinical significance of steroid hormone receptors, two membrane-bound receptors (ERRγ and GPER), and several genes involved in epigenetic alterations. The findings may contribute to revealing events driving tumorigenesis and may aid prognosis. Methods: Using mRNA from diffuse and intestinal GC tumor samples, the expression level of 11 genes, including those coding for sex hormone receptors (estrogen receptors ERα and ERβ), progesterone receptor (PR) and androgen receptor (AR), and the putative relevant ERRγ and GPER receptor were determined by RT-qPCR. Results: In diffuse GC, the expression of ERα, ERβ, PR and AR differed from their expression in the intestinal subtype. The expression of ERα and ERβ was strongly increased in the diffuse subtype compared to the intestinal subtype (×1.90, p = 0.001 and ×2.68, p = 0.002, respectively). Overexpression of ERα and ERβ was observed in diffuse GC (15 and 42%, respectively). The expression levels of PR and AR were strongly decreased in the intestinal subtype as compared to diffuse GC (×0.48, p = 0.005 and ×0.25, p = 0.003, respectively; 37.5% and 56% underexpression). ERα, ERβ, PR and AR showed notable differences for clinicopathological correlation in the diffuse and intestinal GC. A significant decrease of ERα, ERβ, PR and AR in intestinal GC correlated with the absence of lymphatic invasion and lower TNM (I-II). In diffuse GC, among the hormone receptors, increases of ERs and PR mainly correlated with expression of growth factors and receptors (IGF1, FGF7 and FGFR1), and with genes involved in epithelial-mesenchymal transition (VIM and ZEB2) or cell migration (MMP2). Our results also report the strong decreased expression of ERRγ and GPER (two receptors that bind estrogen or xenoestrogens) in diffuse and intestinal subtypes. Conclusions: Our study identified new target genes, namely hormone receptors and membrane receptors (ERRγ and GPER), whose expression is associated with an aggressive phenotype of diffuse GC, and revealed the importance of epigenetic factors (EZH2, HOTAIR, H19 and DNMT1) in gastric cancers. Full article

Global warming raises surface water temperatures, impacting fish alongside pollutants, such as ubiquitous xenoestrogens. Combined stressor effects are poorly studied but likely to worsen impacts and hinder biota adaptation, warranting further research. Unadapted fish face heightened risks. The liver is a vital metabolic organ, sensitive to temperature and xenoestrogens, eventually adjusting hepatocyte size and number to ensure survival, growth, and reproduction. This study assessed, for the first time, the impact of exposure (45 days) to thermal stress (29 °C versus 26 °C) and ethinylestradiol (EE2, 5 ng/L) on male guppies, primarily on body and quantitative liver morphology. Higher temperature reduced body mass (14%) and standard length (3.6%) gain. EE2 exposure reduced body mass increase (14%), hepatosomatic index (20%), and the volumes of the liver (32%), hepatocytes (16%), and their nuclei (17%). The nucleus-to-cytoplasm ratio and total hepatocyte number remained stable. No histopathological lesions existed. Guppies appear to have adapted to stressors by reducing hepatocyte size and utilizing lipid reserves, yet they exhibited deficits in body growth and hepatosomatic index. Gonadal maturation was unaffected. Only under EE2 at 29 °C did hepatocytes show minimal lipid droplet content (less vacuolation). This indicated exhausted reserves, reinforcing how heat and toxicants interact to exacerbate impacts. Full article

Background/Objectives: Bisphenol A (BPA) is found throughout the environment and exposure to it has been shown to cause several health problems, including cancer. The problem with BPA is that it is a xenoestrogen that is chemically very similar to 17β-estradiol. Chronic exposure to BPA overstimulates the estrogen receptors and leads to inflammation that triggers several pathways leading to cancer progression. This is especially true in the case of hormone-sensitive breast cancers. This article reviewed the main pathways thought to be involved in the formation and/or progression of the most common forms of hormone-sensitive breast cancers due to BPA exposure. The main results were compiled and presented in tables along with a more detailed discussion of each pathway within the text. In most cases, chronic BPA exposure led to inflammation, which then triggered pathways leading to cancer stem cell formation and maintenance. In other cases, BPA exposure led to the formation of reactive oxygen species that damaged DNA and caused the formation of mutated p53 and tumorigenesis. Conclusions: The article summarizes the key pathways that are currently known, pertaining to how BPA leads to the progression and maintenance of breast cancer. The article then concludes by discussing how prenatal and perinatal BPA exposure may also predispose women to hormone-sensitive breast cancers later in life. Full article

A biochar (BC) generated by the pyrogasification of wood chips from authorized forestry cuts was extensively characterized and evaluated for its efficacy in retaining/releasing two agrochemicals, namely the fungicide penconazole (PEN), the herbicide S-metolachlor (S-MET), and the xenoestrogen bisphenol A (BPA) widely present in industrial effluents. The elemental composition of BC was evaluated using CN elemental analysis and total reflection X-ray fluorescence (TXRF) spectroscopy which showed the abundance of elements typically found in BCs (Ca, K, P) along with essential trace elements such as Fe and Mn. Scanning electron microscopy coupled with energy-dispersive X-ray analysis (SEM-EDX) described the surface features of BC along with the major surface elements, while Brunauer–Emmett–Teller (BET) analysis revealed, as expected, a large specific surface area (366 m² g⁻¹). High porosity (0.07 cm³ g⁻¹) was demonstrated by the density functional theory (DFT) method, while Fourier transform infrared (FT-IR) spectroscopy highlighted the presence of a prominent aromatic structure and the abundance of reactive functional groups responsible for the binding of the compounds. The sorption/desorption capacity of BC was studied by means of sorption kinetics and isotherms in batch trials, and by modeling the experimental data with various theoretical equations. All compounds reached sorption equilibrium on BC very rapidly, following preferentially pseudo-second-order kinetics. Freundlich adsorption constants of PEN, S-MET, and BPA were 37.3, 13.2, and 11.6 L g⁻¹, respectively, thus demonstrating the great affinity of BC for hydrophobic pollutants. The adsorption process was hysteretic as only a small fraction of each compound was slowly desorbed from BC. The overall results obtained highlighted the great potential of BC of acting as a biosorbent of contaminants, which is of great importance for the containment of pollution in agricultural soils and for limiting the entry of toxic compounds into the human and animal food chain. 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

The concentrations of estrogens and xenoestrogens in the environment are rising rapidly, posing significant and multifaceted risks to human health and ecosystems. It is imperative for governments to develop policies that leverage sustainable technologies to mitigate the presence of pharmaceutical estrogenic compounds in the environment. This review examines the global environmental and human health risks associated with indigenous estrogens and synthetic pharmaceutical xenoestrogens, while critically evaluating sustainable approaches to their management. A total of 28 studies, published between December 2013 and 18 January 2024, and sourced from PubMed and Scopus, were systematically reviewed. Most of these studies focused on estrogenic compounds in aquatic environments where they contribute to reproductive and developmental abnormalities in fish and may enter the human food chain, primarily through fish consumption. Sustainable methods for removing or neutralizing estrogenic compounds include adsorption, filtration, and enzymatic degradation. Additionally, technologies such as activated sludge processes and high-rate algal ponds demonstrate promise for large-scale applications; however, further research and standardized operational guidelines are needed to optimize their efficiency and sustainability. This review has concluded that ECs can have severe consequences on the environment, most notably, impairment of reproductive functions in fish and humans, underscoring the urgent need for governments to implement drug take-back programs, establish evidence-based guidelines for wastewater and pharmaceutical waste treatment, and set enforceable thresholds for estrogenic compounds in surface and drinking water. Existing regulations such as the UK’s Regulation on the registration, evaluation, authorization, and restriction of chemicals and the United States’ National Primary Drinking Water Regulations can be modified to include ECs as dangerous chemicals to aid in maintaining safe EC levels”. Such measures are critical for reducing the environmental concentrations of pharmaceutical estrogenic compounds and safeguarding both public health and ecological integrity. Full article

Xenoestrogens (XEs) are a group of exogenous substances that may interfere with the functioning of the endocrine system. They may mimic the function of estrogens, and their sources are plants, water or dust, plastic, chemical agents, and some drugs. Thus, people are highly exposed to their actions. Together with the development of industry, the number of XEs in our environment increases. They interact directly with estrogen receptors, disrupting the transmission of cellular signals. It is proven that XEs exhibit clinical application in e.g., menopause hormone therapy, but some studies observed that intense exposure to XEs leads to the progression of various cancers. Moreover, these substances exhibit the ability to cross the placental barrier, therefore, prenatal exposure may disturb fetus development. Due to the wide range of effects resulting from the biological activity of these substances, there is a need for this knowledge to be systematized. This review aims to comprehensively assess the environmental sources of XEs and their role in increasing cancer risk, focusing on current evidence of their biological and pathological impacts. Full article

Three-dimensional (3D) fish hepatocyte cultures are promising alternative models for replicating in vivo data. Few studies have attempted to characterise the structure and function of fish 3D liver models and illustrate their applicability. This study aimed to further characterise a previously established spheroid model obtained from juvenile brown trout (Salmo trutta) primary hepatocytes under estrogenic stimulation. The spheroids were exposed for six days to environmentally relevant concentrations of 17α-ethinylestradiol—EE2 (1–100 ng/L). The mRNA levels of peroxisome (catalase—Cat and urate oxidase—Uox), lipid metabolism (acyl-CoA long chain synthetase 1—Acsl1, apolipoprotein AI—ApoAI, and fatty acid binding protein 1—Fabp1), and estrogen-related (estrogen receptor α—ERα, estrogen receptor β—ERβ, vitellogenin A—VtgA, zona pellucida glycoprotein 2.5—ZP2.5, and zona pellucida glycoprotein 3a.2—ZP3a.2) target genes were evaluated by quantitative real-time polymerase chain reaction. Immunohistochemistry was used to assess Vtg and ZP protein expressions. At the highest EE2 concentration, VtgA and ZP2.5 genes were significantly upregulated. The remaining target genes were not significantly altered by EE2. Vtg and ZP immunostaining was consistently increased in spheroids exposed to 50 and 100 ng/L of EE2, whereas lower EE2 levels resulted in a weaker signal. EE2 did not induce significant changes in the spheroids’ viability and morphological parameters. This study identified EE2 effects at environmentally relevant doses in trout liver spheroids, indicating its usefulness as a proxy for in vivo impacts of xenoestrogens. Full article

Oestrogen plays a crucial physiological role in both women and men. It regulates reproductive functions and maintains various non-reproductive tissues through its receptors, such as oestrogen receptor 1/oestrogen receptor α (ESR1/Erα), oestrogen receptor 2/oestrogen receptor β (ESR2/Erβ), and G protein-coupled oestrogen receptor 1 (GPER). This hormone is essential for the proper functioning of women’s ovaries and uterus. Oestrogen supports testicular function and spermatogenesis in men and contributes to bone density, cardiovascular health, and metabolic processes in both sexes. Nuclear receptors Er-α and Er-β belong to the group of transcription activators that stimulate cell proliferation. In the environment, compounds similar in structure to the oestrogens compete with endogenous hormones for binding sites to receptors and to disrupt homeostasis. The lack of balance in oestrogen levels can lead to infertility, cancer, immunological disorders, and other conditions. Exogenous endocrine-active compounds, such as bisphenol A (BPA), phthalates, and organic phosphoric acid esters, can disrupt signalling pathways responsible for cell division and apoptosis processes. The metabolism of oestrogen and its structurally similar compounds can produce carcinogenic substances. It can also stimulate the growth of cancer cells by regulating genes crucial for cell proliferation and cell cycle progression, with long-term elevated levels linked to hormone-dependent cancers such as breast cancer. Oestrogens can also affect markers of immunological activation and contribute to the development of autoimmune diseases. Hormone replacement therapy, oral contraception, in vitro fertilisation stimulation, and hormonal stimulation of transgender people can increase the risk of breast cancer. Cortisol, similar in structure to oestrogen, can serve as a biomarker associated with the risk of developing breast cancer. The aim of this review is to analyse the sources of oestrogens and their effects on the endogenous and exogenous process of homeostasis. Full article

Endocrine-disrupting chemicals (EDCs) have become so pervasive in our environment and daily lives that it is impossible to avoid contact with such compounds, including pregnant women seeking to minimize exposures to themselves and their unborn children. Developmental exposure of humans and rodent models to bisphenol A (BPA) and other EDCs is linked to increased anxiogenic behaviors, learning and memory deficits, and decreased socio-sexual behaviors. Prenatal exposure to BPA and other EDCs leads to longstanding and harmful effects on gut microbiota with reductions in beneficial bacteria, i.e., gut dysbiosis, and such microbial changes are linked to host changes in fecal metabolites, including those involved in carbohydrate metabolism and synthesis, and neurobehavioral alterations in adulthood, in particular, social and cognitive deficits. Gut dysbiosis is increasingly being recognized as a key driver of a myriad of diseases, ranging from metabolic, cardiovascular, reproductive, and neurobehavioral disorders via the gut-microbiome–brain axis. Thus, EDCs might induce indirect effects on physical and mental health by acting as microbiome-disrupting chemicals. Findings raise the important question as to whether pregnant women should consume a probiotic supplement to mitigate pernicious effects of EDCs, especially BPA, on themselves and their unborn offspring. Current studies investigating the effects of maternal probiotic supplementation on pregnant women’s health and that of their unborn offspring will be reviewed. Data will inform on the potential application of probiotic supplementation to reverse harmful effects of EDCs, especially BPA, in pregnant women unwittingly exposed to these compounds and striving to give their offspring the best start in life. Full article

Ten new decalin polyketides, zosteropenilline M (1), 11-epi-8-hydroxyzosteropenilline M (2), zosteropenilline N (3), 8-hydroxyzosteropenilline G (4), zosteropenilline O (5), zosteropenilline P (6), zosteropenilline Q (7), 13-dehydroxypallidopenilline A (8), zosteropenilline R (9) and zosteropenilline S (10), together with known zosteropenillines G (11) and J (12), pallidopenilline A (13) and 1-acetylpallidopenilline A (14), were isolated from the ethyl acetate extract of the fungus Penicillium yezoense KMM 4679 associated with the seagrass Zostera marina. The structures of isolated compounds were established based on spectroscopic methods. The absolute configurations of zosteropenilline Q (7) and zosteropenilline S (10) were determined using a combination of the modified Mosher’s method and ROESY data. The absolute configurations of zosteropenilline M (1) and zosteropenilline N (3) were determined using time-dependent density functional theory (TD-DFT) calculations of the ECD spectra. A biogenetic pathway for compounds 1–14 is proposed. The antimicrobial, cytotoxic and cytoprotective activities of the isolated compounds were also studied. The significant cytoprotective effects of the new zosteropenilline M and zosteropenillines O and R were found in a cobalt chloride (II) mimic in in vitro hypoxia in HEK-293 cells. 1-Acetylpallidopenilline A (14) exhibited high inhibition of human breast cancer MCF-7 cell colony formation with IC₅₀ of 0.66 µM and its anticancer effect was reduced when MCF-7 cells were pretreated with 4-hydroxitamoxifen. Thus, we propose 1-acetylpallidopenilline A as a new xenoestrogen with significant activity against breast cancer. 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

Soybean is a pulse which has considerable nutritional value due to its high protein, fibers and polyunsaturated fatty acid (PUFA) contents. It also contains phytoestrogenic compounds that definitely hinder its recommendation for general consumption. Contrary to ancient times, when soybeans were boiled, modern commercial soy foods can contain up to 150 mg/100g of estrogenic isoflavones. Interestingly, current estimations of isoflavone intake in the literature do not distinguish between the origins of soy food, i.e., whether it is homemade or commercial. As a result, the isoflavone exposure in Asian countries may well be overestimated. This study aims to demonstrate, based on step-by-step monitoring of isoflavones, that traditional and domestic treatments, leveraging isoflavones water-solubility, can indeed significantly reduce their content in soy foods. Indeed, when compared to commercial foods, the isoflavone content was found to be 20, 2.6, 4.5 and 9.8 times lower in “homemade” soy juice, tofu, tempeh and miso, respectively. Additionally, water soaking was found to reduce the isoflavones levels in soy-textured proteins by more than 70%. Hence, this simple process has the potential to help drastically reduce overall xenoestrogens exposure. This study could serve as a basis for establishing the isoflavones Reference Dose and issuing food safety guidelines. Full article

Although male breast cancer (MBC) is globally rare, its incidence significantly increased from 1990 to 2017. The aim of this study was to examine variations in the trends of MBC incidence between populations in Taiwan and the USA from 1980 to 2019. The Taiwan Cancer Registry database and the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute of the USA were used. The age-standardized incidence rate was calculated using the world standard population in 2000. The long-term trends of the age, time period, and birth cohort effect on MBC incidence rates were estimated using the SEER Age-Period-Cohort Web Tool. The results revealed that the incidence of MBC in both countries increased from 2010 to 2019 (Taiwan: average annual percentage change (AAPC) = 2.59%; USA: AAPC = 0.64%). The age and period effects on the incidence rates in both countries strengthened, but the cohort effect was only identified in Taiwan (Rate ratio: 4.03). The identified cohort effect in this study bears resemblance to that noted in a previous investigation on female breast cancer in Taiwan. This suggests the possible presence of common environmental factors influencing breast cancer incidence in both genders, such as a high fat diet and xenoestrogen. Full article