Weak Estrogenic Activity Research Articles

12334 Harnessing Protective Diets: Phytoestrogens As A Strategy To Alleviate Estradiol-driven Progression And Symptomatology In Endometriosis

Abstract Disclosure: A.D. Strong: None. S. Andrisse: None. D. Antani: None. Endometriosis (EMS) is a prevalent gynecological disorder affecting 10% of reproductive-age women with up to 50% experiencing infertility. It is characterized by the presence of endometrial-like tissue outside the uterus, leading to symptoms such as pelvic pain and infertility. While the exact cause of EMS remains elusive, hormonal dysregulation and the succeeding inflammation play a crucial role in its pathogenesis. Phytoestrogens (PEs) are a diverse group of plant-derived compounds that exhibit structural and functional similarities to endogenous estrogens and have emerged as potential therapeutic agents due to their ability to modulate hormonal signaling and inflammatory pathways. This integrative review aimed to provide a summation of the current evidence on the mechanisms of action and potential therapeutic applications of PEs in the context of EMS. PEs exhibit weak estrogenic activity and can interact with estrogen receptors (ERs), influencing hormonal and molecular pathways relevant to the pathology. These compounds have shown promise in regulating estrogen levels, inhibiting cell proliferation, and modulating insulin-like growth factor 1 signaling, all of which are critical in developing and progressing the disease state. Notably, curcumin and resveratrol have demonstrated anti-proliferative effects on endometrial cells by targeting key pathways involved in cell growth and angiogenesis. Curcumin has been shown to downregulate inflammatory factors like COX-2 and TNF-α while reducing vascular endothelial growth factor expression associated with angiogenesis. Similarly, resveratrol has been found to suppress inflammatory responses in endometrial stromal cells through the sirtuin 1 pathway. Studies indicate PEs can enhance antioxidant defenses and counteract reactive oxygen species levels implicated in endometriotic pain and disease progression. By restoring antioxidant balance and mitigating oxidative damage, PEs may offer therapeutic benefits in managing EMS symptoms. In conclusion, their multifaceted effects on estrogen signaling, inflammation, and oxidative stress highlight their potential as adjunctive or alternative treatments for symptomatic women with active disease. Plausible evidence supports that certain dietary components can reduce or exacerbate inflammation associated with EMS symptoms and progression. Foods that are rich in phytoestrogens include soy, fruits, vegetables, spinach, sprouts, beans, cabbages, and grain. Specifically, curcumin is a primary component in turmeric and resveratrol is found in high amounts in black and red grapes, red wine, berries, and nuts. While more research is still needed to fully understand the relationship between diet and endometriosis, utilizing therapeutic dietary interventions appears to be a promising self-management strategy for improving quality of life and symptom management. Presentation: 6/3/2024

Estrogenic Prenylated Flavonoids in Sophora flavescens.

Sophora flavescens is a medicinal herb distributed widely in Japan and it has been used to treat various diseases and symptoms. To explore its pharmacological use, we examined the estrogenic activity of four prenylated flavonoids, namely kurarinone, kushenols A and I, and sophoraflavanone G, which are characterized by the lavandulyl group at position 8 of ring A, but have variations in the hydroxyl group at positions 3 (ring C), 5 (ring A) and 4' (ring B). These prenylated flavonoids were examined via cell proliferation assays using sulforhodamine B, Western blotting, and RT-PCR, corresponding to cell, protein, and transcription assays, respectively, based on estrogen action mechanisms. All the assays employed here found weak but clear estrogenic activities for the prenylated flavonoids examined. Furthermore, the activities were inhibited by an estrogen receptor antagonist, suggesting that the activities were likely being mediated by the estrogen receptors. However, there were differences in the activity, attributable to the hydroxyl group at position 4', which is absent in kushenol A. While the estrogenic activity of kurarinone and sophoraflavanone G has been reported before, to the best of our knowledge, there are no such reports on kushenols A and I. Therefore, this study represents the first report of their estrogenic activity.

Bisphenol A triggers apoptosis in mouse pre-antral follicle granulosa cells via oxidative stress

BackgroundBisphenol A (BPA), an endocrine disrupting chemical with weak estrogenic and anti-androgenic activity, is widely present in various environmental media and organisms. It has certain reproductive toxicity and can cause a variety of female reproductive system diseases. Although BPA-stimulated apoptosis of granulosa cells has been widely elaborated, the effect of BPA on mouse pre-antral follicle granulosa cells (mpGCs) has not been well elucidated.ResultsIn this study, the results of live-dead cell staining showed that high concentrations of BPA severely impaired mpGCs growth viability and affected the cell cycle transition of mpGCs. We confirmed that BPA promotes the production of reactive oxygen species (ROS) and facilitates oxidative stress in mpGCs. In addition, immunofluorescence, transmission electron microscopy, and flow cytometry experiments demonstrated that BPA treatment for mpGCs resulted in apoptotic features, such as rounding, cytoplasmic crinkling, and mitochondrial damage. This was accompanied by a large production of ROS and apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus. RNA-seq data showed that several apoptosis-related pathways were enriched in the high concentration BPA-treated group compared with the normal group, such as the p53 pathway, MAPK pathway, etc.ConclusionsThese results suggest that cells undergo oxidative stress effects and apoptosis after BPA treatment for mpGCs, which affects normal follicle development. The potential mechanism of BPA-induced female reproductive toxicity was elucidated, while providing a research basis for the prevention and treatment of female reproductive diseases.

Fermentation of soybeans with Pleurotus cornucopiae and Pleurotus ostreatus increases isoflavone aglycones, total polyphenol content and antioxidant activity.

Edible basidiomycetes are highly active in the oxidative decomposition and polymerisation of polyphenols, and soybeans contain large amounts of isoflavones, which are polyphenol glycosides. Isoflavone aglycones exhibit weak estrogenic activities. In this study, we investigated the isoflavone content, polyphenol production, antioxidant activity and ergothioneine (EGT) content of soybeans fermented by Pleurotus cornucopiae and Pleurotus ostreatus. Isoflavone glycosides, which were abundant in unfermented soybeans, decreased, and aglycones increased on day 10 of culture in both edible basidiomycete-fermented soybeans. The total maximum polyphenol content in soybeans fermented by both mushrooms were approximately 4 times higher on day 30 to 40 of culture, than that of unfermented soybeans. P. cornucopiae-fermented soybeans showed maximum antioxidant activity on day 20 of culture, and this was approximately 6.1 times higher than that of unfermented soybeans. EGT was not detected in unfermented soybeans, whereas both fermented soybeans showed a maximum EGT content on day 20 of culture, which was especially high in P. cornucopiae-fermented soybeans. The antioxidant activity and EGT of P. cornucopiae-fermented soybeans were higher than those of P. ostreatus, suggesting that EGT was responsible for the increase in the antioxidant activity of P. cornucopiae-fermented soybeans.

THE CHEMICAL COMPOSITION OF PARABEN AND ITS EFFECTS ON HEALTH

Parabens are a group of alkyl esters of p-hydroxybenzoic acid and usually include methyl paraben, ethyl paraben, propyl paraben, butyl paraben, isobutyl paraben, isopropyl paraben and benzyl paraben. Parabens (or their salts) are widely used as preservatives in cosmetics and medicine due to their relatively low toxicity and long history of safe use. Testing of parabens has shown, to varying degrees, that individual paraben compounds have weak estrogenic activity in some in vitro screening tests, such as estrogen receptor ligand binding, regulation of CAT gene expression, and proliferation of MCF-7 cells. Reported in vivo effects include uterine weight gain (eg, butyl, isobutyl, and benzyl parabens) and male reproductive tract effects (eg, butyl and propyl parabens). However, in relation to estrogen as a control during in vivo studies, parabens are much less active than estrogen. While exposure to sufficient doses of exogenous estrogens can increase the risk of certain adverse effects, it is hypothesized that similar risks may arise from exposure to much weaker endocrine-active chemicals (EACs) is still speculation. In evaluating the possibility that exposure to weakly active EACs may be associated with adverse effects due to their endocrine mode of action, it is important to consider both the dose and potency of these compounds compared to estrogen. In this review, a comparative approach involving dose and potency is used to assess whether in utero or adult exposure to parabens may be associated with adverse effects due to their estrogen-modulating mode of action. Keywords: parabens, p-Hydroxybenzoates, PHBA, paraben applications, Methyl paraben.

Specific Application of Punicagranatum Linn

Throughout the world, pomegranates are a popular therapeutic and nutritive fruit. punicagranatum.L (Punicaceae) plays a significant role in medicine. It has an intriguing pharmacological activity on each compartment of the pomegranate. Certain segments, such as the juice, leaf, flower, and peels, possess strong antioxidant properties, while the juice, peel, and oil have weak estrogenic activity. The following major properties include anti-inflammatory, antioxidant, nephroprotective, hepatoprotective, anti-oxidant, anti-cancer, Overview of the punicagranatum L.'s chemical composition, traditional use, phytochemistry, pharmacology, and toxicology current information about the punicaceae is provided.

Ultrasensitive Fluorescent “ON-OFF” Label-Free Immunosensor for Detection of Vitellogenin of Marine Medaka

The negative effects of environmental estrogens on wildlife and human beings are gaining increasing attention. Research on the highly sensitive detection method for Vitellogenin (Vtg), one of the biomarkers of environmental estrogens (EEs), is expected to detect weak estrogens in complex environments. This study aimed to develop a label-free immunosensor with high specificity and sensitivity for testing Vtg. Carbon quantum dots (CQDs) with high fluorescence and excellent stability were synthesized, and antilipovitellin monoclonal antibody (Anti-Lv-mAb) was prepared. Based on the fluorescence resonance energy transfer (FRET) between CQDs-conjugated Anti-Lv-mAb and reduced graphene oxide (RGO), an ultrasensitive fluorescent “ON-OFF” label-free immunosensor for detection of Vtg of marine medaka was established. By modification of RGO with poly dimethyl diallyl ammonium chloride (PDDA), the Zeta potential of RGO was changed and the FRET efficiency was improved. The immunosensor displayed a wide linear response to Vtg of marine medaka from 0.1 to 3000 ng/mL, a low limit of detection (LOD) of 0.04 ng/mL, and excellent sensitivity (28,833.63 CPS/(ng/mL)), selectivity, and reproducibility. The results demonstrated that the fluorescent “ON-OFF” immunosensor is an easy-to-use, relatively fast, ultrasensitive, and accurate detection method for weak estrogenic activity.

P-647 Intake of soy foods and soy isoflavones in relation to ovarian reserve among women presenting to a fertility center

Abstract Study question Are soy food and isoflavone intakes associated with ovarian reserve as measured by antral follicle count (AFC)? Summary answer Within the observed range of intake, soy food or isoflavone consumptions are not associated with AFC. What is known already Phytoestrogens are structurally similar to 17β-estradiol, and bind to ER-α and ER-β in vitro resulting in weak estrogenic activity. Previous work in ruminants, felines and rodents has shown that exposure to phytoestrogens can have major adverse impacts on reproduction. However, findings of studies in humans suggest that soy foods and soy phytoestrogens may not have major deleterious impacts on reproductive hormone levels or reproductive outcomes, and could even be beneficial in couples undergoing infertility treatment. Study design, size, duration Women presenting to a large academic fertility center between April 2007 and December 2019 were invited to participate in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study. Intake of 15 soy-based foods during the previous three months was obtained at baseline and intake of soy phytoestrogens was estimated from these reports. AFC was assessed with transvaginal ultrasound performed as part of diagnostic evaluation for infertility. Participants/materials, setting, methods We included 667 women who reported their soy food intake and had an AFC assessment. Women were divided in groups of increasing soy food and soy isoflavone intake with women who reported not consuming soy-based foods serving as the reference group. We evaluated the association of soy foods and soy isoflavones intake with AFC using Poisson regression models adjusting for confounders. Analyses were also stratified by age, BMI, and smoking status. Main results and the role of chance Women had median baseline age of 35.0 years and BMI of 23.4 kg/m2. Mean (range) intake of soy foods was 0.1 (0-7.4) servings/day, and mean (range) intake of isoflavones was 6 (0-166) mg/day, which is comparable to that of women in the general population of the USA. Intakes of soy foods or isoflavones were not related to AFC. The median (IQR) AFC for women who did not consume soy foods and women in the highest category of soy intake (>0.45 servings/day, median 0.88 servings/day) were 12 (9, 18) and 13 (9, 19). After adjustment for potential confounders, the mean difference in AFC between women in the highest category of soy intake and women who did not consume soy was -0.5% (-6.6%, 6.1%). Soy food intake remained unrelated to AFC when intake was categorized using different cutoff values when intake was modeled as a continuous variable when departures from a linear association were considered, and when we excluded from analysis 76 women whose AFC ultrasound scan was performed before they completed the diet assessment. Soy intake was also unrelated to AFC within categories of age, BMI and smoking status. Findings for soy isoflavones mirrored those for soy-food intake. Limitations, reasons for caution Self-reported soy intake may have resulted in measurement error leading to attenuation of observed relations towards the null. Also, all participants were women presenting to a fertility center and therefore, findings may not be generalizable to women in the general population. Wider implications of the findings Our findings suggest soy food and isoflavone intakes within the ranges observed among women in the general population of the USA is unlikely to influence ovarian reserve in any meaningful way. Trial registration number Not applicable

Preparation of Graphene Quantum Dots by Visible-Fenton Reaction and Ultrasensitive Label-Free Immunosensor for Detecting Lipovitellin of Paralichthys Olivaceus.

The increasing levels of environmental estrogens are causing negative effects on water, soil, wildlife, and human beings; label-free immunosensors with high specificities and sensitivities are being developed to test estrogeneous chemicals in complex environmental conditions. For the first time, highly fluorescent graphene quantum dots (GQDs) were prepared using a visible-Fenton catalysis reaction with graphene oxide (GO) as a precursor. Different microscopy and spectroscopy techniques were employed to characterize the physical and chemical properties of the GQDs. Based on the fluorescence resonance energy transfer (FRET) between amino-functionalized GQDs conjugated with anti-lipovitellin monoclonal antibodies (Anti-Lv-mAb) and reduced graphene oxide (rGO), an ultrasensitive fluorescent “ON-OFF” label-free immunosensor for the detection of lipovitellin (Lv), a sensitive biomarker derived from Paralichthys olivaceus for environmental estrogen, has been established. The immunosensor has a wide linear test range (0.001–1500 ng/mL), a lower limit of detection (LOD, 0.9 pg/mL), excellent sensitivity (26,407.8 CPS/(ng/mL)), and high selectivity and reproducibility for Lv quantification. The results demonstrated that the visible-Fenton is a simple, mild, green, efficient, and general approach to fabricating GQDs, and the fluorescent “ON-OFF” immunosensor is an easy-to-use, time-saving, ultrasensitive, and accurate detection method for weak estrogenic activity.

In Silico, In Vitro, and In Vivo Evaluation of the Developmental Toxicity, Estrogenic Activity, and Mutagenicity of Four Natural Phenolic Flavonoids at Low Exposure Levels.

Flavonoids are bioactive phenolic compounds widely present in plant food and used in various nutraceutical, pharmaceutical, and cosmetic products. However, recent studies showed rising concerns of endocrine disruptions and developmental toxicities for many flavonoids. To understand the impacts of flavonoid structure on toxicity, we used a new multitiered platform to investigate the toxicities of four common flavonoids, luteolin, apigenin, quercetin, and genistein, from flavone, flavonol, and isoflavone. Weak estrogenic activity was detected for four flavonoids (genistein, apigenin, quercetin, and luteolin) at 10–12 to 10–7 M by the MCF-7 cell proliferation assay, which agreed with the molecular docking results. Consistent with the simulation results of Toxicity Estimation Software Tool, genistein and luteolin showed high developmental toxicity in the chicken embryonic assay (45–477 μg/kg) with mortality rate up to 50%. Luteolin, quercetin, and apigenin showed signs of mutagenicity at 5 × 10–3 pmol/plate. The findings showed nonmonotonic dose responses for the chemicals.

Challenging Approach to the Development of Novel Estrogen Receptor Modulators Based on the Chemical Properties of Guaiazulene.

Tamoxifen, a therapeutic agent for breast cancer, has been associated with genetic polymorphisms in the metabolism of N,N-dialkylaminoethyl substituent, which plays an important role in the expression of selective estrogen receptor modulator (SERM) activity. To solve this problem, we developed a novel estrogen receptor (ER) modulator, Az-01, on the basis of the aromaticity, dipole moment, and isopropyl group of guaiazulene. Az-01 showed four-fold lower binding affinity for ER than E2 but had similar ER-binding affinity to that of 4-hydroxytamoxifen (4-HOtam). Unlike tamoxifen, Az-01 acted as a partial agonist with very weak estrogenic activity at high concentrations when used alone, and it showed potent anti-estrogenic activity in the presence of E2. The cell proliferation and inhibition activities of Az-01 were specific to ER-expressing MCF-7 cells, and no effect of Az-01 on other cell proliferation signals was observed. These findings are important for the development of new types of SERMs without the N,N-dialkylaminoethyl substituent as a privileged functional group for SERMs.

Development of the electrochemical and molecular dynamics approaches toward the monitoring of biomolecular interaction between DNA and the intercalative endocrine disruptor; Bisphenol A

Damage to DNA by environmental pollutants mostly result in several chronic diseases. Bisphenol A (BPA), an environmental oestrogen inducing weak estrogenic activity, has raised concerns due to its carcinogenic and DNA damaging potential. On account of developing a feasible and reliable methodology for high performance dsDNA damage indirect monitoring, an electrochemical biosensing device was constructed relying on the unique properties of multi-walled carbon nanotubes (MWCNTs) and using methylene blue (MB) as the electroactive probe. The fabricated electrochemical device was subjected to electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and field emission scanning electron microscope (FESEM) for characterization. Various factors affecting the biosensor performance were optimized. Also, the obtained oxidation signals were applied for indirect detection of BPA and the lowest limit of detection (LOD) was calculated to be 15 nM. Moreover, a molecular dynamic study was further developed to get better insight into the interaction between dsDNA and BPA.

Ultrasensitive label-free electrochemical immunosensors for detecting marine medaka (Oryzias melastigma) vitellogenin based on novel Cu2O–BSA nanoparticles and anti-lipovitellin monoclonal antibody

Vitellogenin (Vtg) is a biomarker for environmental estrogens, and its sensitive detection method is vital for the detection of weak estrogenic activity. This study aimed to develop sensitive electrochemical immunosensors for marine medaka (Oryzias melastigma) Vtg based on novel nanomaterials. Firstly, Cu2O–BSA nanoparticles (NPs) with a diameter of 120−150 nm was synthesized, and monoclonal antibody against lipovitellin (anti-Lv mAb) was prepared. Then two simple and efficient label-free immunosensors for the detection of Vtg were established using Cu2O–BSA NPs and gold nanoparticle (Au NPs) as signal amplification elements and anti-Lv mAb as the detection probe. These two immunosensors have good sensitivity, selectivity, reproducibility for Vtg quantification, and are easy to use. Moreover, the BSA/Anti-Lv mAb/Au/Cu2O–BSA/GCE immunosensor exhibited a linear range from 0.128 to 5 × 104 pg/mL, with the lowest detection limit (LOD) of 0.09 pg/mL, which is considerably lower than those of the previously reported Vtg detection techniques. Finally, the performance of the immunosensor was evaluated by quantifying Vtg concentrations in plasma of male marine medaka exposed three estrogenic bisphenols. The results demonstrated that the BSA/Anti-Lv mAb/Au/Cu2O–BSA/GCE immunosensor was an easily-operated, ultrasensitive and accurate detection method for weak estrogenic activity.

N-Butyl Benzyl Phthalate Exposure Promotes Lesion Survival in a Murine Endometriosis Model

Endometriosis is an inflammatory and estrogen-dependent gynecological disease associated with exposure to environmental endocrine disruptors. n-Butyl benzyl phthalate (BBP), a ubiquitous plasticizer, has weak estrogenic activity, and exposure to BBP is associated with endometriosis. We aimed to elucidate the immunomodulatory effect of BBP on endometriosis development. We previously established a surgery-induced endometriosis-like murine model. In the present study, we exposed those mice to BBP 10 days prior to surgery and 4 weeks after surgery at physiologically relevant doses to mimic human exposure. Chronic exposure to BBP did not promote the growth of endometriotic lesions; however, the lesion survival rate in BBP-treated mice did increase significantly compared with control mice. Multiparametric flow cytometry showed that BBP exposure did not affect the homeostasis of infiltrated immune subsets in lesions but did enhance CD44 (adhesion marker) expression on plasmacytoid dendritic cells (pDCs). Blocking CD44 interactions locally inhibited endometriotic lesion growth. Immunofluorescence results further confirmed that CD44 blocking inhibited pDC infiltration and reduced the frequency of CD44+ pDCs in endometriotic tissues. BBP also disrupted the estrus cycle in these mice. This study suggests that chronic exposure to low-dose BBP may promote survival of endometriotic tissue through CD44-expressing pDCs.

Actions of edamame soybean isoflavones in an avian model: the Japanese quail (Cortunix-cortunix japónica)

Isoflavone are soybean compounds that possess weak estrogenic and antiestrogenic activities. The present study examined the effect of extract isoflavone of edamame soybean supplementation into the poultry ration to increasing production and reproduction performance of Japanese quail hens. The research was an experimental observation applying Complete Randomized Design. The treatment done was supplementation of the extract isoflavone into the ration, quantitatively, i.e P0 : 0% (group control), P1 : 0.1%, P2 : 0.3%, and P3 : 05%, in every single treatment consists of 5 repetitions of 10 quails each. The level isoflavone of edamame soybean were 0.0015% for deidzein and 0.0013% for genistein. The treatment was done for fourteen days old quail until its sexual maturity. Observation was conducted for the growth, feed intake, age at sexual maturity, weight of the first laying egg, cholesterol egg and performance of production in quail hens. The results of experiment indicate that the addition of extract isoflavone in the ration did not exert an effect on reproductive performance, and egg production of female quail (p>0.05). There was a tendency that the supplementation of extract isoflavone could increase in sexual maturity and reduce cholesterol egg of quail. It is concluded that the supplementation of extract isoflavone of edamame soybean up to 0.5% has not been able to improve production and reproductive performance and reduce cholesterol levels of quail egg.

Chicken embryonic toxicity and potential in vitro estrogenic and mutagenic activity of carvacrol and thymol in low dose/concentration

Thymol and carvacrol are phenolic isomers with the potential developmental toxicity and endocrine disruptions (ED) at low concentrations. However, few reports estimated their toxicity and ED below 10−6 M (150 μg/L) (MW of thymol and carvacrol: 150 g/mol). In this study, both chemicals were determined for the developmental toxicity and potential ED at 500 μg/kg and 50 μg/kg using the chicken embryonic assay, potential estrogenic activity (EA) at 10−12 to 10−7 M (1.5 × 10−4 to 15 μg/L) by the MCF-7 cell proliferation assay, mutagenicity at 10−12 to 10−6 M (1.5 × 10−4 to 150 μg/L) by the Ames test, and an in silico method for ED. Carvacrol showed mutagenic risks at 10−7, 10−8, and 10−11 M (15, 1.5, and 0.0015 μg/L) while thymol at 10−6 and 10−8 M (150 and 1.5 μg/L). Carvacrol negatively impacted embryonic growth at 50 μg/kg, with weak EA at 10−8 M (1.5 μg/L). Carvacrol but not thymol had weak EA at 10−12 M (1.5 × 10−4 μg/L). Molecular docking to 14 types of hormone-related receptors revealed that carvacrol had higher binding affinities to two estrogen receptors and the mineralocorticoid receptor than those to thymol. Carvacrol and thymol varied in toxicities due to a different location of one phenolic hydroxyl group.

Phytoestrogens for Cancer Prevention and Treatment.

Simple SummaryPhytoestrogens are compounds derived from plants that have a similar structure to human sex hormones. This has led to the observation that phytoestrogens have comparable effects to these hormones in our cells. Some beneficial effects of phytoestrogens include the improvement of menopausal symptoms and the prevention of several diseases. In fact, the consumption of soy and soy foods among the Asian population has been associated with a decrease in the incidence of some types of tumors. However, there are some concerns about whether these compounds may also have harmful effects, such as interfere with cancer treatments. In this review, we collect data on the reported effects of phytoestrogens alone or in combination with anti-cancer treatments and discuss the controversy around using these compounds.Phytoestrogens are a large group of natural compounds found in more than 300 plants. They have a close structural similarity to estrogens, which allow them to bind to both estrogen receptors (ER), ERα and ERβ, presenting a weak estrogenic activity. Phytoestrogens have been described as antioxidant, anti-inflammatory, anti-thrombotic, anti-allergic, and anti-tumoral agents. Their role in cancer prevention has been well documented, although their impact on treatment efficiency is controversial. Several reports suggest that phytoestrogens may interfere with the effect of anti-cancer drugs through the regulation of oxidative stress and other mechanisms. Furthermore, some phytoestrogens could exert a protective effect on healthy cells, thus reducing the secondary effects of cancer treatment. In this review, we have studied the recent research in this area to find evidence for the role of phytoestrogens in cancer prevention and therapy efficacy.

A prominent environmental endocrine disruptor, 4-nonylphenol, promotes endometriosis development via plasmacytoid dendritic cells.

Endometriosis is an estrogen-dependent chronic inflammatory disease and is associated etiologically with environmental endocrine disruptor (EED) exposure. 4-nonylphenol (NP), a widely found EED, has weak estrogenic activity and modulates plasmacytoid dendritic cell (pDC) function in vitro and in vivo. We aimed to elucidate the immunomodulatory effect of NP on the development of endometriosis, particularly focusing on pDCs. This study established a surgically induced endometriosis murine model (C57BL/6) under conditions of NP treatment that are relevant to the level and route of human exposure. Multi-parametric flow cytometry was used for analysis of infiltrated immune cell subsets in lesions. The results showed that NP exposure significantly promoted endometriotic lesion growth, survival and angiogenesis development of lesions as well as pDC accumulation in the lesions in mice. Adoptive transfer of NP-conditioned pDCs into mice significantly enhanced lesion development and local pDC infiltration, whereas NP-conditioned conventional dendritic cells did not affect lesion growth. In vitro functional analysis showed that NP-conditioned pDCs in lesions expressed high levels of CD36, a scavenger receptor and NP-conditioned splenic pDCs secreted an enhanced level of IL-10 in response to apoptotic cell recognition in a CD36-dependent manner. Furthermore, we observed that local treatment with blocking antibodies against IL-10 and CD36 on the day of surgery significantly inhibited lesion development. NP exposure also altered the estrous cycle in mice. The results suggest that chronic and low-dose exposure to NP enhances endometriotic lesion growth by altering pDC homeostasis and function. This study has important implications for understanding the environment-innate immunity interaction in human endometriosis.

Identification of health risks from harmful chemical agents – review concerning bisphenol A in workplace

Abstract Bisphenol A (BPA) is an industrial chemical used as an additive in conventional point-of-sale thermal paper receipts, in the production of many polycarbonate plastics, and epoxy resins lignin for food. BPA is xenoestrogen, a foreign compound that is not naturally produced in living organisms, but which acts similarly to natural 17-ß estradiol (natural estrogen). Due to its weak estrogenic activities, BPA exposure may influence multiple endocrine-related pathway, and is associated with prostate and breast cancer, neurobehavioral deficits, heart disease, and obesity. Furthermore, BPA may act as a DNA methylation agent and cause altered gene expression in the brain. Human exposure to bisphenol A is a matter of controversy. This review shows a potential risks in workplace resulting from contact with bisphenol A. The work presents the contribution of BPA exposure levels via dermal contact and the relationship between BPA exposure level and oxidative DNA damage.

2,2',4,4'-tetrabromodipheny ether (BDE-47) disrupts gonadal development of the Africa clawed frog (Xenopus laevis)

Previous studies have shown that BDE-47, one of the most abundant polybrominated diphenyl ethers (PBDEs) congeners, has a weak estrogenic activity, but it has remained unclear whether BDE-47 disrupts gonadal development and causes male-to-female sex reversal in lower vertebrates, with limited and controversial data. The present study aimed to determine the effects of BDE-47 on gonadal development in Xenopus laevis, a model amphibian species for studying adverse effects of estrogenic chemicals on reproductive development. X. laevis at stage 45/46 were exposed to BDE-47 (0.5, 5, 50 nM) in semi-static system, with 1 nM 17β-estradiol (E2) as the positive control. When reaching stage 53, tadpoles were examined for gonadal morphology, histology and sex-dimorphic gene expression. The phenotypic sex (gonadal morphology and histology) of each BDE-47-treated tadpole matched its genetic sex, showing no sex-reversal, whereas one half of genetic males treated with E2 displayed ovarian-like features. However, some genetic males (26%) in the 50 nM BDE-47 treatment group were found to contain more germ cells clumping together in the medulla, along with an increasing tendency of the gonad length/kidney length ratio in males, resembling feminizing outcomes of E2. These observations seem to suggest that BDE-47 exerted weak feminizing effects. However, BDE-47 induced increases in expression of both female-biased genes and male-biased genes in two sexes, which disagrees with feminizing outcomes, suggesting complicated effects of BDE-47 on gonadal development. Taken together, all results demonstrate that nanomolar BDE-47 disrupted gonadal development and exerted weak feminizing effects, but not resulted in male-to-female sex reversal in X. laevis.