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1.
Chemosphere ; 345: 140312, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37863209

RESUMO

To investigate the degradation efficiency of conditioners and commercial microbial agents on estrogens (E1, 17α-E2, 17ß-E2, E3, EE2, and DES) in the composting process of dairy manure, seven different treatments (RHB-BF, OSP-BF, SD-BF, MR-BF, MR-FS, MR-EM, and MR-CK) under forced ventilation conditions were composted and monitored regularly for 30 days. The results indicated that the removal rates of estrogens in seven treatments ranged from 95.35% to 99.63%, meanwhile the degradation effect of the composting process on 17ß-Estradiol equivalent (EEQ) was evaluated, and the removal rate of ΣEEQ ranged from 96.42% to 99.72%. With the combined addition of rice husk biochar (RHB) or oyster shell powder (OSP) and bio-bacterial fertilizer starter cultures (BF), namely RHB-BF and OSP-BF obviously promoted the rapid degradation of estrogens. 17ß-E2 was completely degraded on the fifth day of composting in OSP-BF. Microbial agents have some promotional effect and enhances the microbial degradation of synthetic estrogen (EE2, DES). According to the results of RDA, pH and EC were the main environmental factors affecting on the composition and succession of estrogen-related degrading bacteria in composting system. As predominant estrogens-degrading genera, Acinetobacter, Bacillus, and Pseudomonas effected obviously on the change of estrogens contents. The research results provide a practical reference for effective composting of dairy manure to enhancing estrogens removal and decreasing ecological risk.


Assuntos
Compostagem , Congêneres do Estradiol , Estrogênios/metabolismo , Esterco , Estradiol/metabolismo , Solo/química
2.
PLoS One ; 18(3): e0280421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36928065

RESUMO

A synthetic estrogen, diethylstilbestrol (DES), is known to cause adult vaginal carcinoma by neonatal administration of DES to mice. However, the carcinogenic process remains unclear. By Cap Analysis of Gene Expression method, we found that neonatal DES exposure up-regulated inflammatory Cxcl chemokines 2, 3, 5, and 7 located in the 5qE1 region in the vaginal epithelium of mice 70 days after birth. When we examined the gene expressions of these genes much earlier stages, we found that neonatal DES exposure increased these Cxcl chemokine genes expression even after 17 days after birth. It implies the DES-mediated persistent activation of inflammatory genes. Intriguingly, we also detected DES-induced non-coding RNAs from a region approximately 100 kb far from the Cxcl5 gene. The non-coding RNA up-regulation by DES exposure was confirmed on the 17-day vagina and continued throughout life, which may responsible for the activation of Cxcl chemokines located in the same region, 5qE1. This study shows that neonatal administration of DES to mice causes long-lasting up-regulation of inflammatory Cxcl chemokines in the vaginal epithelium. DES-mediated inflammation may be associated with the carcinogenic process.


Assuntos
Quimiocinas CXC , Dietilestilbestrol , Congêneres do Estradiol , Animais , Feminino , Camundongos , Animais Recém-Nascidos , Carcinógenos/farmacologia , Dietilestilbestrol/efeitos adversos , Dietilestilbestrol/farmacologia , Epitélio/patologia , Congêneres do Estradiol/efeitos adversos , Congêneres do Estradiol/farmacologia , Vagina/metabolismo , Neoplasias Vaginais/induzido quimicamente , Quimiocinas CXC/efeitos dos fármacos , Quimiocinas CXC/metabolismo
3.
Chemosphere ; 317: 137893, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36690257

RESUMO

Synthetic estrogens are emerging environmental contaminants with great estrogenic activities and stable structures that are widespread in various ecological systems and significantly threaten the health of organisms. Pseudomonas citronellolis SJTE-3 is reported to degrade the synthetic estrogen 17α-ethynylestradiol (EE2) efficiently in laboratory conditions. In this work, the environmental adaptability, the EE2-degrading properties, and the ecological effects of P. citronellolis SJTE-3 under different hostile conditions (heavy metals and surfactants) and various natural environment samples (solid soil, lake water, and pig manure) were studied. Strain SJTE-3 can tolerate high concentrations of Zn2+ and Cr3+, but is relatively sensitive to Cu2+. Tween 80 of low concentration can significantly promote EE2 degradation by strain SJTE-3, different from the repressing effect of Triton X-100. High concentration of Tween 80 prolonged the lagging phase of EE2-degrading process, while the final EE2 removal efficiency was improved. More importantly, strain SJTE-3 can grow normally and degrade estrogen stably in various environmental samples. Inoculation of strain SJTE-3 removed the intrinsic synthetic and natural estrogens (EE2 and estrone) in lake water samples in 4 days, and eliminated over 90% of the amended 1 mg/L EE2 in 2 days. Bioaugmentation of strain SJTE-3 in EE2-supplied solid soil and pig manure samples achieved a removal rate of over 55% and 70% of 1 mg/kg EE2 within 2 weeks. Notably, the bioaugmentation of extrinsic strain SJTE-3 had a slight influence on indigenous bacterial community in pig manure samples, and its relative abundance decreased significantly after EE2 removal. Amendment of EE2 or strain SJTE-3 in manure samples enhanced the abundance of Proteobacteria and Actinobacteria, implying their potential in utilizing EE2 or its metabolites. These findings not only shed a light on the environment adaptability and degradation efficiency of strain SJTE-3, but also provide insights for bioremediation application in complex and synthetic estrogen polluted environments.


Assuntos
Congêneres do Estradiol , Microbiota , Poluentes Químicos da Água , Animais , Suínos , Polissorbatos , Esterco , Etinilestradiol/análise , Congêneres do Estradiol/metabolismo , Estrogênios/análise , Estrona/análise , Água/análise , Solo , Poluentes Químicos da Água/análise
4.
Sci Total Environ ; 861: 160594, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36455722

RESUMO

The synthetic estrogen 17α-ethinylestradiol (EE2) is a common component of hormone therapy and oral contraceptives and has been widely used for nearly 60 years. Numerous studies have shown that exposure to EE2 can affect embryonic development in a number of fish species. The effects of parental and embryonic EE2 exposure on embryo developmental toxicity and the underlying molecular mechanisms, however, have rarely been examined. In this study, embryos collected from parental EE2-exposed adult fish were examined to assess EE2-induecd toxicity during embryo development. The rate of embryo development including heart rate, hatching rate, and larval locomotion were measured to assess embryo developmental toxicity. The embryonic transcriptome was used to delineate the related developmental toxicity pathways. Our results suggest that parental and embryonic EE2 exposure resulted in growth retardation including a reduction in embryo heart rate, a delay in the appearance eye pigmentation, decreased hatching rate and impaired larval locomotion. In addition, gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Ingenuity Pathway Analysis (IPA) of transcriptome revealed that these impairments are controlled by estrogen receptor and related to eye structure, neuronal and synaptic structure, and behaviour. The key factors identified, including PRKAA2, APOB, EPHB2, OXTR, NR2E3, and POU4F2, could serve as biomarkers for assessing EE2-induced embryo developmental toxicity. For the first time, our results show that eye pigmentation is a potentially sensitive marker of EE2-induced embryo developmental toxicity.


Assuntos
Congêneres do Estradiol , Oryzias , Poluentes Químicos da Água , Animais , Oryzias/fisiologia , Etinilestradiol/toxicidade , Congêneres do Estradiol/farmacologia , Transcriptoma , Larva , Desenvolvimento Embrionário , Poluentes Químicos da Água/toxicidade
5.
Cancer J ; 28(3): 163-168, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35594462

RESUMO

ABSTRACT: In 1971, Sir Alexander Haddow et al. delivered the inaugural David A. Karnofsky lecture at the American Society for Clinical Oncology. This award was designated American Society for Clinical Oncology's highest, as he had used translational research to identify the first clinical therapy, that is, synthetic estrogens to treat breast cancer. His lecture was entitled "Thoughts on Chemical Therapy." For 40 years, high-dose synthetic estrogens were used as palliative therapy, for some advanced breast cancer patients 5 years following menopause. Mechanisms were unknown. Tamoxifen, a failed "morning-after pill," is an antiestrogen in estrogen receptor-positive breast cancer, which was subsequently used to treat all stages of breast cancer and to prevent breast cancer. In 2008, Jordan was selected to present the 38th Karnofsky lecture entitled: "The Paradoxical Action of Estrogen in Breast Cancer-Survival or Death?" Unexpectedly, through a study of acquired resistance to long-term tamoxifen therapy, estrogen-induced apoptosis in long-term estrogen-deprived breast cancer was deciphered in Jordan's laboratory. These data and the biological rules established under laboratory conditions provided molecular mechanisms to aid in the interpretation of the Women's Health initiative in the United States and the Million Women Study in the United Kingdom. In addition, by establishing laboratory models to understand mechanisms of estrogen-induced apoptosis, new estrogen derivatives were successfully evaluated in the laboratory and tested as candidates for women after the therapeutic failure of antiestrogenic strategies to treat breast cancer. For the future, the knowledge obtained about estrogen-induced apoptosis in cancer holds the promise of discovering new therapies to control or cure cancer in general.


Assuntos
Neoplasias da Mama , Congêneres do Estradiol , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , Congêneres do Estradiol/uso terapêutico , Estrogênios/farmacologia , Estrogênios/uso terapêutico , Feminino , Humanos , Masculino , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico
6.
Bioresour Technol ; 349: 126857, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35183727

RESUMO

Synthetic estrogenic compounds such as 17α-ethinylestradiol (EE2) are significant environmental contaminants. This research studied the biodegradation of EE2 utilizing the EE2 adapted cells isolated from a dairy farm waste site in suspension flask vis-a-vis Bioelectrochemical System (BES) and compared the power output in the BES with and without EE2 as a co-substrate. 78% removal of EE2 was observed in the BES as against 60% removal in suspension flasks. The maximum power density in the BES increased about 53% when EE2 is used as a co-substrate. The EE2 biodegradation studied using HPLC and Q-TOF methods, also proposes a hypothetical pathway for EE2 degradation by the newly isolated strain Rhodopseudomonas palustris MDOC01 and reports the significant metabolites like nicotinic acid and oxoproline being detected during bioelectrochemical treatment process of EE2. Study also suggests that Plasma peroxide treatment of anode material enhanced the overall performance in terms of biodegradation efficiency and power output.


Assuntos
Congêneres do Estradiol , Poluentes Químicos da Água , Biodegradação Ambiental , Congêneres do Estradiol/análise , Congêneres do Estradiol/metabolismo , Etinilestradiol/química , Espectrometria de Massas , Poluentes Químicos da Água/química
7.
Nanotechnology ; 33(7)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34727533

RESUMO

This study focuses on the adsorption kinetics of four highly potent sex hormones (estrone (E1), 17ß-estradiol (E2), 17α-ethinylestradiol (EE2), and estriol (E3)), present in water reservoirs, which are considered a major cause of fish feminization, low sperm count in males, breast and ovarian cancer in females induced by hormonal imbalance. Herein, electrospun polymeric nanostructures were produced from cellulose acetate, polyamide, polyethersulfone, polyurethanes (918 and elastollan), and polyacrylonitrile (PAN) to simultaneously adsorbing these estrogenic hormones in a single step process and to compare their performance. These nanofibers possessed an average fiber diameter in the range 174-330 nm and their specific surface area ranged between 10.2 and 20.9 m2g-1. The adsorption-desorption process was investigated in four cycles to determine the effective reusability of the adsorption systems. A one-step high-performance liquid chromatography technique was developed to detect and quantify concurrently each hormone present in the solution. Experimental data were obtained to determine the adsorption kinetics by applying pseudo-first-order, pseudo-second-order and intraparticle diffusion models. Findings showed that E1, E2 and EE2 best fitted pseudo-second-order kinetics, while E3 followed pseudo-first-order kinetics. It was found that polyurethane Elastollan nanofibers had maximum adsorption capacities of 0.801, 0.590, 0.736 and 0.382 mg g-1for E1, E2, EE2 and E3, respectively. In addition, the results revealed that polyurethane Elastollan nanofibers had the highest percentage efficiency of estrogens removal at ∼58.9% due to its strong hydrogen bonding with estrogenic hormones, while the least removal efficiency for PAN at ∼35.1%. Consecutive adsorption-desorption cycles demonstrated that polyurethane maintained the best efficiency, even after being repeatedly used four times compared to the other polymers. Overall, the findings indicate that all the studied nanostructures have the potential to be effective adsorbents for concurrently eradicating such estrogens from the environment.


Assuntos
Técnicas Eletroquímicas/métodos , Disruptores Endócrinos , Congêneres do Estradiol , Nanofibras/química , Poluentes Químicos da Água , Adsorção , Disruptores Endócrinos/química , Disruptores Endócrinos/metabolismo , Disruptores Endócrinos/farmacocinética , Congêneres do Estradiol/química , Congêneres do Estradiol/metabolismo , Congêneres do Estradiol/farmacocinética , Cinética , Membranas Artificiais , Poluentes Químicos da Água/química , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/farmacocinética , Purificação da Água
8.
Neurotox Res ; 39(6): 2029-2041, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34797527

RESUMO

Newly synthesized Pathway Preferential Estrogen-1 (PaPE-1) selectively activates membrane estrogen receptors (mERs), namely, mERα and mERß, and has been shown to evoke neuroprotection; however, its effectiveness in protecting brain tissue against hypoxia and ischemia has not been verified in a posttreatment paradigm. This is the first study showing that a 6-h delayed posttreatment with PaPE-1 inhibited hypoxia/ischemia-induced neuronal death, as indicated by neutral red uptake in mouse primary cell cultures in vitro. The effect was accompanied by substantial decreases in neurotoxicity and neurodegeneration in terms of LDH release and Fluoro-Jade C staining of damaged cells, respectively. The mechanisms of the neuroprotective action of PaPE-1 also involved apoptosis inhibition demonstrated by normalization of both mitochondrial membrane potential and expression levels of apoptosis-related genes and proteins such as Fas, Fasl, Bcl2, FAS, FASL, BCL2, BAX, and GSK3ß. Furthermore, PaPE-1-evoked neuroprotection was mediated through a reduction in ROS formation and restoration of cellular metabolic activity that had become dysregulated due to hypoxia and ischemia. These data provide evidence that targeting membrane non-GPER estrogen receptors with PaPE-1 is an effective therapy that protects brain neurons from hypoxic/ischemic damage, even when applied with a 6-h delay from injury onset.


Assuntos
Isquemia Encefálica , Congêneres do Estradiol , Hipóxia Encefálica , Indanos , Receptores de Estrogênio , Animais , Camundongos , Isquemia Encefálica/tratamento farmacológico , Caspase 3/metabolismo , Células Cultivadas , Congêneres do Estradiol/uso terapêutico , Hipóxia Encefálica/tratamento farmacológico , Indanos/farmacologia , Indanos/uso terapêutico , L-Lactato Desidrogenase/metabolismo , Neurônios/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Receptores de Estrogênio/efeitos dos fármacos
9.
Biomolecules ; 11(9)2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34572598

RESUMO

Inhibition of K+-conductance through the human ether-a-go-go related gene (hERG) channel leads to QT prolongation and is associated with cardiac arrhythmias. We previously reported that physiological concentrations of some estrogens partially suppress the hERG channel currents by interacting with the S6 residue F656 and increase the sensitivity of hERG blockade by E-4031. Although these studies suggested that clinically used synthetic estrogens with similar structures have the marked potential to alter hERG functions, the hERG interactions with synthetic estrogens have not been assessed. We therefore examined whether ethinylestradiol (EE2), a synthetic estrogen used in oral contraceptives, affects hERG function and blockade by drugs. Supratherapeutic concentrations of EE2 did not alter amplitudes or kinetics of the hERG currents elicited by train pulses at 20 mV (0.1 Hz). On the other hand, EE2 at therapeutic concentrations reduced the degree of hERG current suppression by E-4031. The administration of EE2 followed by E-4031 blockade reversed the current suppression, suggesting that the interaction of EE2 and E-4031 alters hERG at the drug-binding site. The effects of EE2 on hERG blockade raised the possibility that other estrogens, including synthetic estrogens, can alter hERG blockade by drugs that cause QT prolongation and ventricular arrhythmias.


Assuntos
Congêneres do Estradiol/farmacologia , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Etinilestradiol/farmacologia , Piperidinas/farmacologia , Piridinas/farmacologia , Congêneres do Estradiol/química , Canais de Potássio Éter-A-Go-Go/metabolismo , Etinilestradiol/química , Células HEK293 , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Piperidinas/química , Piridinas/química
10.
Neuropharmacology ; 198: 108756, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34416269

RESUMO

Women have more difficulty maintaining smoking cessation than men, and experience greater withdrawal symptomatology as well as higher prevalence of relapse. Further, currently available treatments for smoking cessation, such as the nicotine patch and varenicline, have been shown to be less effective in women. Fluctuations in ovarian hormones across the menstrual cycle can affect craving and smoking relapse propensity. In addition, many women who smoke use some form of oral contraceptives, which most often contain ethinyl estradiol (EE), a synthetic, orally bio-available estrogen that is currently prescribed to women chronically and has been shown to alter smoking reward in women. The current study examined the impact of 17ß-estradiol (E2), the prominent endogenous form of the steroid hormone estrogen, as well as EE, on nicotine self-administration, demand, and reinstatement following ovariectomy (OVX) or sham surgery. OVX vehicle-treated female rats consumed less nicotine, had lower intensity of demand, and reinstated less compared to sham vehicle-treated female rats. OVX-E2 and OVX-EE treatment groups showed a rebound of nicotine intake later in training, and Q0 levels of consumption were partially rescued in both groups. Further, E2 but not EE reversed the abolishment of reinstated nicotine seeking induced by OVX. Taken together, these results demonstrate that natural and synthetic estrogens play a critical role in mediating the neurobehavioral effects of nicotine, and future studies are essential for our understanding of how synthetic hormones contained within oral contraceptives interact with smoking.


Assuntos
Comportamento de Procura de Droga/efeitos dos fármacos , Congêneres do Estradiol/farmacologia , Estradiol/farmacologia , Estrogênios/farmacologia , Tabagismo/psicologia , Animais , Fumar Cigarros/psicologia , Sinais (Psicologia) , Etinilestradiol/farmacologia , Feminino , Ovariectomia , Ratos , Ratos Long-Evans , Recidiva , Recompensa , Autoadministração
11.
Sci Rep ; 11(1): 2767, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531587

RESUMO

Synthetic estrogens such as ethinylestradiol (EE2) are persistent micropollutants that are not effectively removed from wastewater by conventional treatments. These contaminants are released into waterbodies, where they disrupt endocrine systems of organisms and cause harmful effects such as feminization, infertility, reproduction problems and genital malformations. The consequences of this pollution for key marine ecosystems such as coral reefs and their associated microbiomes are underexplored. We evaluated the effects of EE2 concentrations of 100 ng L-1 and 100 µg L-1 on the coral metaorganism Mussismilia harttii. The results indicated no effects on visible bleaching or Fv/Fm ratios in the corals during a 17-day microcosm experiment. However, next-generation sequencing of 16S rDNA revealed a statistically significant effect of high EE2 concentrations on OTU richness, and shifts in specific microbial groups after treatments with or without EE2. These groups might be bioindicators of early shifts in the metaorganism composition caused by EE2 contamination.


Assuntos
Antozoários/efeitos dos fármacos , Recifes de Corais , Congêneres do Estradiol/toxicidade , Etinilestradiol/toxicidade , Poluentes Químicos da Água/toxicidade , Animais
12.
Pharmacol Res ; 165: 105423, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33434621

RESUMO

Brain derived neurotrophic factor (BDNF) promotes maturation of dopaminergic (DAergic) neurons in the midbrain and positively regulates their maintenance and outgrowth. Therefore, understanding the mechanisms regulating the BDNF signaling pathway in DAergic neurons may help discover potential therapeutic strategies for neuropsychological disorders associated with dysregulation of DAergic neurotransmission. Because estrogen-related receptor gamma (ERRγ) is highly expressed in both the fetal nervous system and adult brains during DAergic neuronal differentiation, and it is involved in regulating the DAergic neuronal phenotype, we asked in this study whether ERRγ ligand regulates BDNF signaling and subsequent DAergic neuronal phenotype. Based on the X-ray crystal structures of the ligand binding domain of ERRγ, we designed and synthesized the ERRγ agonist, (E)-4-hydroxy-N'-(4-(phenylethynyl)benzylidene)benzohydrazide (HPB2) (Kd value, 8.35 µmol/L). HPB2 increased BDNF mRNA and protein levels, and enhanced the expression of the BDNF receptor tropomyosin receptor kinase B (TrkB) in human neuroblastoma SH-SY5Y, differentiated Lund human mesencephalic (LUHMES) cells, and primary ventral mesencephalic (VM) neurons. HPB2-induced upregulation of BDNF was attenuated by GSK5182, an antagonist of ERRγ, and siRNA-mediated ERRγ silencing. HPB2-induced activation of extracellular-signal-regulated kinase (ERK) and phosphorylation of cAMP-response element binding protein (CREB) was responsible for BDNF upregulation in SH-SY5Y cells. HPB2 enhanced the DAergic neuronal phenotype, namely upregulation of tyrosine hydroxylase (TH) and DA transporter (DAT) with neurite outgrowth, both in SH-SY5Y and primary VM neurons, which was interfered by the inhibition of BDNF-TrkB signaling, ERRγ knockdown, or blockade of ERK activation. HPB2 also upregulated BDNF and TH in the striatum and induced neurite elongation in the substantia nigra of mice brain. In conclusion, ERRγ activation regulated BDNF expression and the subsequent DAergic neuronal phenotype in neuronal cells. Our results might provide new insights into the mechanism underlying the regulation of BDNF expression, leading to novel therapeutic strategies for neuropsychological disorders associated with DAergic dysregulation.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/biossíntese , Neurônios Dopaminérgicos/metabolismo , Congêneres do Estradiol/farmacologia , Glicoproteínas de Membrana/biossíntese , Receptor trkB/biossíntese , Receptores de Estrogênio/metabolismo , Regulação para Cima/fisiologia , Animais , Fator Neurotrófico Derivado do Encéfalo/química , Linhagem Celular Tumoral , Neurônios Dopaminérgicos/efeitos dos fármacos , Congêneres do Estradiol/química , Feminino , Humanos , Ligantes , Masculino , Glicoproteínas de Membrana/química , Camundongos , Camundongos Endogâmicos C57BL , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Fenótipo , Gravidez , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Ratos , Ratos Sprague-Dawley , Receptor trkB/química , Receptores de Estrogênio/química , Regulação para Cima/efeitos dos fármacos
13.
Int J Mol Sci ; 21(23)2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33266302

RESUMO

Breast cancer (BC) is the second most common cancer and the fifth deadliest in the world. Exposure to endocrine disrupting pollutants has been suggested to contribute to the increase in disease incidence. Indeed, a growing number of researchershave investigated the effects of widely used environmental chemicals with endocrine disrupting properties on BC development in experimental (in vitro and animal models) and epidemiological studies. The complex effects of endocrine disrupting chemicals (EDCs) on hormonal pathways, involving carcinogenic effects and an increase in mammary gland susceptibility to carcinogenesis-together with the specific characteristics of the mammary gland evolving over the course of life and the multifactorial etiology of BC-make the evaluation of these compounds a complex issue. Among the many EDCs suspected of increasing the risk of BC, strong evidence has only been provided for few EDCs including diethylstilbestrol, dichlorodiphenyltrichloroethane, dioxins and bisphenol A. However, given the ubiquitous nature and massive use of EDCs, it is essential to continue to assess their long-term health effects, particularly on carcinogenesis, to eradicate the worst of them and to sensitize the population to minimize their use.


Assuntos
Neoplasias da Mama/etiologia , Suscetibilidade a Doenças , Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Compostos Benzidrílicos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , DDT , Congêneres do Estradiol/metabolismo , Feminino , Humanos , Fenóis , Medição de Risco , Fatores de Risco
14.
Folia Med Cracov ; 60(2): 81-95, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-33252597

RESUMO

BACKGROUND: Uterine leiomyoma is the most widespread benign tumor affecting women of childbearing age. There are still gaps in the understanding of its pathogenesis. Telocytes are unique cells found in more than 50 different locations inside the human body. The functional relationship between cells could clarify the pathogenesis of leiomyomata. Examination of membrane receptors on telocytes could explain their role in fibrosis, oxidative stress, and myometrial contractility. AIM: This research was conducted to assess the density of telocytes in terms of their putative role in leiomyoma formation by focusing on their correlation with the expression of estrogen and progesterone receptors. METHODS: For gross evaluation of uterine tissue samples from leiomyoma, routine histology of adjacent and unaffected myometrium was performed. Immunohistochemical analysis of c-kit, tryptase, CD34, PDGFRα (telocyte-specific), and ER and PRs (estrogen and progesterone receptors) was performed to examine uterine telocytes and the expression of sex steroid receptors. RESULTS: The decline in telocyte density in leiomyoma foci was correlated with high progesterone expression and low estrogen receptor expression. The unchanged myometrium showed the opposite correlation and balance between both steroid hormone receptors. The difference in sex steroid receptor expression is correlated with the density of uterine telocytes, which emphasizes their conductor function. CONCLUSIONS: A reduction in telocyte density and the changes in examined marker expression demonstrate the involvement of telocytes in local homeostasis. The expression of membrane receptors explicitly indicates their functional potential in the human myometrium, focusing attention on contractility and local homeostasis.


Assuntos
Congêneres do Estradiol/farmacocinética , Leiomioma/diagnóstico por imagem , Leiomioma/patologia , Progesterona/farmacocinética , Telócitos/efeitos dos fármacos , Telócitos/fisiologia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Adulto , Idoso , Congêneres do Estradiol/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Polônia , Progesterona/fisiologia
15.
Horm Behav ; 126: 104848, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32918873

RESUMO

The increased prevalence of neurodevelopmental disorders during the last half-century led us to investigate the potential for intergenerational detrimental neurodevelopmental effects of synthetic female gonadal hormones, typically used in contraceptive pills. We examined 3 separate cohorts of mice over the span of 2 years, a total of 150 female F0 mice and over 300 male and female rodents from their F1 progeny. We demonstrate that F1 male offsprings of female mice previously exposed to the synthetic estrogen 17α-ethinylestradiol (EE2) in combination with the synthetic progestin Norethindrone, exhibit neurodevelopmental and behavioral differences compared to control mice. Because the EE2 + Norethindrone administration resulted in gene expression changes in the exposed F0 mice ovaries persisting after the end of treatment, it is likely that the synthetic hormone treatment caused changes in the germline cells and that led to altered neurodevelopment in the offsprings. An altered gene expression pattern was discovered in the frontal cortex of male mice from the first offspring (F1.1) at infancy and an ADHD-like hyperactive locomotor behavior was exhibited in young male mice from the second offspring (F1.2) of female mice treated with contraceptive pill doses of EE2 + Norethindrone prior to pregnancy. The intergenerational neurodevelopmental effects of EE2 + Norethindrone treatment were sex specific, predominantly affecting males. Our observations in mice support the hypothesis that the use of synthetic contraceptive hormones is a potential environmental factor impacting the prevalence of human neurodevelopmental disorders. Additionally, our results indicate that contraceptive hormone drug safety assessments may need to be extended to F1 offspring.


Assuntos
Encéfalo/embriologia , Contraceptivos Hormonais/efeitos adversos , Congêneres do Estradiol/efeitos adversos , Exposição Materna/efeitos adversos , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Cognição/efeitos dos fármacos , Etinilestradiol/efeitos adversos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transtornos do Neurodesenvolvimento/induzido quimicamente , Transtornos do Neurodesenvolvimento/fisiopatologia , Gravidez
16.
Sci Total Environ ; 743: 140428, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32763724

RESUMO

17α-ethinylestradiol (EE2) is a synthetic estrogen that can cause harmful effects on animals, such as male feminization and infertility. However, the impact of the EE2 contamination on microbial communities and the potential role of bacterial strains as bioremediation agents are underexplored. The aim of this work was to evaluate the impact of EE2 on the microbial community dynamics of aerated submerged fixed-film reactors (ASFFR) simulating a polishing step downstream of a secondary sewage treatment. For this purpose, the reactors were fed with a synthetic medium with low COD content (around 50 mg l-1), supplemented (reactor H) or not (reactor C) with 1 µg l-1 of EE2. Sludge samples were periodically collected during the bioreactors operation to assess the bacterial profile over time by 16S rRNA gene amplicon sequencing or by bacterial isolation using culture-dependent approach. The results revealed that the most abundant phyla in both reactors were Proteobacteria and Bacteroidetes. At genus level, Chitinophagaceae, Nitrosomonas and Bdellovibrio predominated. Significant effects caused by EE2 treatment and bioreactors operating time were observed by non-metric multidimensional scaling. Therefore, even at low concentrations as 1 µg l-1, EE2 is capable of influencing the bioreactor microbiome. Culture-dependent methods showed that six bacterial isolates, closely related to Pseudomonas and Acinetobacter genera, could grow on EE2 as the sole carbon source under aerobic conditions. These organisms may potentially be used for the assembly of an EE2-degrading bacterial consortium and further exploited for bioremediation applications, including tertiary sewage treatment to remove hormone-related compounds not metabolized in secondary depuration stages.


Assuntos
Congêneres do Estradiol , Microbiota , Animais , Reatores Biológicos , Estrogênios , Etinilestradiol , Masculino , RNA Ribossômico 16S , Esgotos
17.
Environ Pollut ; 266(Pt 1): 114994, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32653741

RESUMO

Very little is currently known regarding the effects of estrogenic endocrine disrupting chemicals on embryonic and larval development in molluscs, nor the potential effects of parental (F0) exposure on resultant F1 offspring. In this study, we assessed the embryotoxic impacts of exposure to environmentally relevant concentrations of the synthetic estrogen, 17α-ethinylestradiol (EE2), to male and female parents (50 ng/L) and their offspring (5 and 50 ng/L) in the native Australian Sydney rock oyster, Saccostrea glomerata. There were no detectable effects of parental exposure on fertilisation success, proportions of early larval (F1) morphs and unfertilised eggs. Offspring impacts were evidenced in terms of developmental delays, with decreased percentages of D-veligers retained by 45 µm mesh, along with a reduction of swimming capabilities of larvae at 2 days post-fertilisation (dpf) when both parents had been exposed to 50 ng/L EE2. Although no significant parental effects were found on the survival of F1 larvae at 9 dpf, retardation of shell growth was observed on F1 larvae in treatments where both parents had been exposed to 50 ng/L EE2. Subsequent larval exposure from 2 to 9 dpf caused declines in survival and reduction of shell length in F1 larvae at both 5 and 50 ng/L EE2 across all parental exposure treatments. Collectively, parental EE2 imparts effects on offspring in terms of retardation of larval development, and subsequent offspring exposure to EE2 further exacerbates impacts to development. Future research should aim to understand the potential mechanisms of EE2 induced toxicity and its transmission resulting in altered phenotypes of the F1 generation.


Assuntos
Disruptores Endócrinos , Congêneres do Estradiol , Ostreidae , Poluentes Químicos da Água , Animais , Austrália , Etinilestradiol , Feminino , Masculino
18.
Toxins (Basel) ; 12(2)2020 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-31991913

RESUMO

Deoxynivalenol (DON) is a highly abundant mycotoxin that exerts many adverse effects on humans and animals. Much effort has been made to control DON in the past, and bio-transformation has emerged as the most promising method. However, useful and effective application of bacterial bio-transformation for the purpose of inhibiting DON remains urgently needed. The current study isolated a novel DON detoxifying bacterium, Slackia sp. D-G6 (D-G6), from chicken intestines. D-G6 is a Gram-positive, non-sporulating bacterium, which ranges in size from 0.2-0.4 µm × 0.6-1.0 µm. D-G6 de-epoxidizes DON into a non-toxic form called DOM-1. Optimum conditions required for degradation of DON are 37-47 °C and a pH of 6-10 in WCA medium containing 50% chicken intestinal extract. Besides DON detoxification, D-G6 also produces equol (EQL) from daidzein (DZN), which shows high estrogenic activity, and prevents estrogen-dependent and age-related diseases effectively. Furthermore, the genome of D-G6 was sequenced and characterized. Thirteen genes that show potential for DON de-epoxidation were identified via comparative genomics. In conclusion, a novel bacterium that exhibits the dual function of detoxifying DON and producing the beneficial natural estrogen analogue, EQL, was identified.


Assuntos
Actinobacteria/metabolismo , Equol/metabolismo , Congêneres do Estradiol/metabolismo , Isoflavonas/metabolismo , Tricotecenos/metabolismo , Actinobacteria/genética , Genoma Bacteriano , Filogenia
19.
Reproduction ; 159(3): 289-302, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31990666

RESUMO

Equine placentitis is associated with alterations in maternal peripheral steroid concentrations, which could negatively affect pregnancy outcome. This study aimed to elucidate the molecular mechanisms related to steroidogenesis and steroid-receptor signaling in the equine placenta during acute placentitis. Chorioallantois (CA) and endometrial (EN) samples were collected from mares with experimentally induced placentitis (n = 4) and un-inoculated gestationally age-matched mares (control group; n = 4). The mRNA expression of genes coding for steroidogenic enzymes (3ßHSD, CYP11A1, CYP17A1, CYP19A1, SRD5A1, and AKR1C23) was evaluated using qRT-PCR. The concentration of these enzyme-dependent steroids (P5, P4, 5αDHP, 3αDHP, 20αDHP, 3ß-20αDHP, 17OH-P, DHEA, A4, and estrone) was assessed using liquid chromatography-tandem mass spectrometry in both maternal circulation and placental tissue. Both SRD5A1 and AKR1C23, which encode for the key progesterone metabolizing enzymes, were downregulated (P < 0.05) in CA from the placentitis group compared to controls, and this downregulation was associated with a decline in tissue concentrations of 5αDHP (P < 0.05), 3αDHP (P < 0.05), and 3ß-20αDHP (P = 0.052). In the EN, AKR1C23 was also downregulated in the placentitis group compared to controls, and this downregulation was associated with a decline in EN concentrations of 3αDHP (P < 0.01) and 20αDHP (P < 0.05). Moreover, CA expression of CYP19A1 tended to be lower in the placentitis group, and this reduction was associated with lower (P = 0.057) concentrations of estrone in CA. Moreover, ESR1 (steroid receptors) gene expression was downregulated (P = 0.057) in CA from placentitis mares. In conclusion, acute equine placentitis is associated with a local withdrawal of progestins in the placenta and tended to be accompanied with estrogen withdrawals in CA.


Assuntos
Corioamnionite/veterinária , Congêneres do Estradiol/biossíntese , Cavalos/metabolismo , Placenta/enzimologia , Progesterona/biossíntese , Animais , Corioamnionite/enzimologia , Corioamnionite/patologia , Feminino , Placenta/patologia , Gravidez
20.
Gen Comp Endocrinol ; 288: 113345, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31812531

RESUMO

Natural and synthetic estrogens and progestins are widely used in human and veterinary medicine and are detected in waste and surface waters. Our previous studies have clearly shown that a number of these substances targets the brain to induce the estrogen-regulated brain aromatase expression but the consequences on brain development remain virtually unexplored. The aim of the present study was therefore to investigate the effect of estradiol (E2), progesterone (P4) and norethindrone (NOR), a 19-nortestosterone progestin, on zebrafish larval neurogenesis. We first demonstrated using real-time quantitative PCR that nuclear estrogen and progesterone receptor brain expression is impacted by E2, P4 and NOR. We brought evidence that brain proliferative and apoptotic activities were differentially affected depending on the steroidal hormone studied, the concentration of steroids and the region investigated. Our findings demonstrate for the first time that steroid compounds released in aquatic environment have the capacity to disrupt key cellular events involved in brain development in zebrafish embryos further questioning the short- and long-term consequences of this disruption on the physiology and behavior of organisms.


Assuntos
Congêneres do Estradiol/farmacologia , Estrogênios/farmacologia , Sistema Nervoso/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Congêneres da Progesterona/farmacologia , Progesterona/farmacologia , Peixe-Zebra/embriologia , Animais , Embrião não Mamífero , Desenvolvimento Embrionário/efeitos dos fármacos , Disruptores Endócrinos/farmacologia , Estradiol/farmacologia , Estrogênios/análogos & derivados , Estrogênios/síntese química , Humanos , Ligantes , Nandrolona/farmacologia , Sistema Nervoso/embriologia , Células Neuroendócrinas/efeitos dos fármacos , Células Neuroendócrinas/fisiologia , Noretindrona/farmacologia , Progesterona/análogos & derivados , Progesterona/síntese química , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/agonistas , Receptores de Progesterona/metabolismo , Peixe-Zebra/crescimento & desenvolvimento
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