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SriDurgaDevi Kolla, Mary Morcos, Brian Martin, Laura N Vandenberg
Throughout life, mammary tissue is strongly influenced by hormones. Scientists have hypothesized that synthetic chemicals with hormonal activities could disrupt mammary gland development and contribute to breast diseases and dysfunction. Bisphenol S (BPS) is an estrogenic compound used in many consumer products. In this study, CD-1 mice were exposed to BPS (2 or 200 μg/kg/day) during pregnancy and lactation. Mice exposed to 0.01 or 1 μg/kg/day ethinyl estradiol (EE2), a pharmaceutical estrogen, were also evaluated...
March 8, 2018: Reproductive Toxicology
Hiroya Kadokawa, Kiran Pandey, Kereilwe Onalenna, Asrafun Nahar
Estrone (E1) and estriol (E3) are considered "weak" estrogens, which exert suppressive effects through estrogen receptors α and β. However, recent studies have demonstrated that E1 and E3, as well as estradiol (E2), suppress gonadotropin-releasing hormone-induced luteinizing hormone secretion from bovine gonadotrophs via G-protein-coupled receptor 30, which is expressed in various reproductive organs. Currently, there is a lack of fundamental knowledge regarding E1 and E3, including their blood levels...
March 6, 2018: Journal of Reproduction and Development
Li Ji, Shujing Ji, Chenchen Wang, Kasper P Kepp
Understanding the bioactivation mechanisms to predict toxic metabolites is critical for risk assessment of phenolic endocrine-disrupting chemicals (EDCs). One mechanism involves ipso-substitution, which may contribute to the total turnover of phenolic EDCs, yet the detailed mechanism and its relationship with other mechanisms are unknown. We used density functional theory to investigate the P450-catalyzed ipso-substitution mechanism of the prominent xenoestrogen bisphenol A. The ipso-substitution proceeds via H-abstraction from bisphenol A by Compound I, followed by essentially barrierless OH-rebound onto the ipso-position forming a quinol, which can spontaneously decompose into the carbocation and hydroquinone...
February 28, 2018: Environmental Science & Technology
D Joseph Jerry, James D Shull, Darryl L Hadsell, Monique Rijnkels, Karen A Dunphy, Sallie S Schneider, Laura N Vandenberg, Prabin Dhangada Majhi, Celia Byrne, Amy Trentham-Dietz
Breast cancer risk is intimately intertwined with exposure to estrogens. While more than 160 breast cancer risk loci have been identified in humans, genetic interactions with estrogen exposure remain to be established. Strains of rodents exhibit striking differences in their responses to endogenous ovarian estrogens (primarily 17β-estradiol). Similar genetic variation has been observed for synthetic estrogen agonists (ethinyl estradiol) and environmental chemicals that mimic the actions of estrogens (xenoestrogens)...
February 27, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Yuki Fujiwara, Wataru Miyazaki, Noriyuki Koibuchi, Takahiko Katoh
Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function...
2018: Frontiers in Endocrinology
Alicia González-González, María Dolores Mediavilla, Emilio J Sánchez-Barceló
The objective of this article is to review the basis supporting the usefulness of melatonin as an adjuvant therapy for breast cancer (BC) prevention in several groups of individuals at high risk for this disease. Melatonin, as a result of its antiestrogenic and antioxidant properties, as well as its ability to improve the efficacy and reduce the side effects of conventional antiestrogens, could safely be associated with the antiestrogenic drugs presently in use. In individuals at risk of BC due to night shift work, the light-induced inhibition of melatonin secretion, with the consequent loss of its antiestrogenic effects, would be countered by administering this neurohormone...
February 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Weili Yang, Wen Tan, Jingfei Zheng, Biyan Zhang, Hongfeng Li, Xuehe Li
Cervical cancer is the fourth leading cause of cancer death in females worldwide and the second leading cause of mortality among women. Estrogenic signals can regulate the progression of cervical cancer, however, little is known about the mono-2-ethyhexyl phthalate (MEHP), an environmental xenoestrogen, on the development of cervical cancers. Our present data showed that nanomolar concentrations of MEHP can trigger the proliferation, while not invasion, of cervical cancer HeLa and SiHa cells, which was confirmed by the results that MEHP can also increase the expression of proliferating cell nuclear antigen (PCNA)...
January 27, 2018: European Journal of Pharmacology
Martyna Pajewska, Mariusz Łojko, Krzysztof Cendrowski, Włodzimierz Sawicki, Tomasz Kowalkowski, Bogusław Buszewski, Renata Gadzała-Kopciuch
Endometrial cancer is one of the most commonly diagnosed cancers in women. The search for factors that contribute to the development of cancer cells in reproductive organs should involve the detection of xenoestrogens, in particular zearalenone (ZEA) and its metabolites. Xenoestrogens are endocrine disruptors-ZEA and its metabolites are structurally similar to estrogens (macrocyclic lactone ring) and show high affinity for estrogen receptors. This study proposes a new method for the preparation of samples of human tissues with endometrial cancer by the use of the QuEChERS technique...
January 24, 2018: Analytical and Bioanalytical Chemistry
Bridget L Bergquist, Kaelyn G Jefferson, Hailey N Kintz, Amorette E Barber, Andrew A Yeagley
Commercially utilized parabens are employed for their antimicrobial properties, but a weak binding to the estrogen receptor alpha (ERα) may lead to breast cancer in some applications. Modification of the paraben scaffold should allow for a disconnection of these observed properties. Toward this goal, various 3,5-substituted parabens were synthesized and assessed for antimicrobial properties against S. aureus as well as competitive binding to the ERα. The minimum inhibitory concentration assay confirmed retention of antimicrobial activity in many of these derivatives, while all compounds exhibited decreased xenoestrogen activity as determined by a combination of competitive enzyme linked immunosorbent assay (ELISA), proliferation, and estrogen receptor binding assay...
January 11, 2018: ACS Medicinal Chemistry Letters
Zhi-Hao Liu, Qi-Liang Chen, Qiang Chen, Fang Li, Ying-Wen Li
In fish, spermatogenesis and somatic growth are mainly regulated by hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-somatic (HPS) axes, respectively. Xenoestrogens have been reported to impair spermatogenesis in some fishes, and arrest somatic growth in some others, whereas, whether xenoestrogens are capable of disrupting spermatogenesis and somatic growth simultaneously in fish that exhibits sexual dimorphic growth is little known, and the underlying mechanisms remain poorly understood. In this study, male juveniles of yellow catfish (Pelteobagrus fulvidraco), which exhibits a sexual dimorphic growth that favors males, were exposed to diethylstilbestrol (DES) for 28 days...
January 16, 2018: Fish Physiology and Biochemistry
Benedikt Warth, Philipp Raffeiner, Ana Granados, Tao Huan, Mingliang Fang, Erica M Forsberg, H Paul Benton, Laura Goetz, Caroline H Johnson, Gary Siuzdak
Recently, the palbociclib/letrozole combination therapy was granted accelerated US FDA approval for the treatment of estrogen receptor (ER)-positive breast cancer. Since the underlying metabolic effects of these drugs are yet unknown, we investigated their synergism at the metabolome level in MCF-7 cells. As xenoestrogens interact with the ER, we additionally aimed at deciphering the impact of the phytoestrogen genistein and the estrogenic mycotoxin zearalenone. A global metabolomics approach was applied to unravel metabolite and pathway modifications...
January 10, 2018: Cell Chemical Biology
Luca Dellafiora, Benedikt Warth, Verena Schmidt, Giorgia Del Favero, Hannes Mikula, Johannes Fröhlich, Doris Marko
Xenoestrogenic mycotoxins may contaminate food and feed posing a public health issue. Besides the zearalenone group, the Alternaria toxin alternariol (AOH) has been described as a potential mycoestrogen. However, the estrogenicity of Alternaria toxins is still largely overlooked and further data are needed to better describe the group toxicity. In the frame of risk assessment, mixed in silico/in vitro approaches already proved to be effective first-line analytical tools. An integrated in silico/in vitro approach was used to investigate the effects of metabolic and chemical modifications on the estrogenicity of AOH...
May 15, 2018: Food Chemistry
Ayman E Shafei, Maggie M Ramzy, Abdelhares I Hegazy, Ahmed K Husseny, Usama G El-Hadary, Mazen M Taha, Ali A Mosa
The endocrine disrupting chemical (EDC) is an exogenous substance or mixture that alters the function of the endocrine system and consequently causes adverse effects in intact organisms. Bisphenol A (BPA), one of the most common endocrine disrupting chemicals is a carbon-based synthetic compound used in the production of water bottles, cans, and teeth suture materials. It is known to be a xenoestrogen as it interacts with estrogen receptors and acts as agonist or antagonist via estrogen receptor-dependent signaling pathways...
January 6, 2018: Gene
Geum-A Lee, Kyung-Chul Choi, Kyung-A Hwang
Triclosan (TCS) and bisphenol A (BPA) are endocrine-disrupting chemicals that interfere with the hormone or endocrine system and may cause cancer. Kaempferol (Kaem) and 3,3'-diindolylmethane (DIM) are phytoestrogens that play chemopreventive roles in the inhibition of carcinogenesis and cancer progression. In this study, the influence of TCS, BPA, Kaem, and DIM on proliferation and apoptotic abilities of VM7Luc4E2 breast cancer cells were examined. MTT assay revealed that TCS (0.1-10 μM), BPA (0.1-10 μM) and E2 (0...
January 9, 2018: Biomolecules & Therapeutics
B Jana, K A Meller, M Czajkowska, J Całka
Elevated levels of endogenous estrogens in the course of pathological states of ovaries, as well as xenoestrogens, may lead to hyperestrogenism. It has previously been demonstrated that long-term estradiol-17β (E2) administration in adult gilts affected the population of sympathetic intraovarian nerve fibers. The aim of this study has been to determine the effect of long-term E2 exposure on the cholinergic innervation pattern of porcine ovaries. Intraovarian distribution and the density of nerve fibers immunoreactive (IR) to vesicular acetylocholine transporter (VAChT) and/or neuronal isoform of nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) were determined...
January 2, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Ana M Molina, Nieves Abril, Noelia Morales-Prieto, José G Monterde, Antonio J Lora, Nahúm Ayala, Rosario Moyano
Given the importance of bisphenol A (BPA) as a xenoestrogen and its potential effects on human and animal health, we evaluated BPA exposure's short-term effects on follicular development, yolk protein vitellogenin (VTG) production and aromatase expression in female zebrafish. Histological modifications were observed along with increased presence of atretic follicles. Whole-body VTG concentration increased with the dose of BPA exposure. In contrast, expression of Cyp19a mRNA in the ovaries of BPA-exposed fish exhibited an apparent non-monotonic response curve, marked by downregulation at 1 μg/L BPA, upregulation at 10 μg/L BPA, and a return to downregulation at 100 μg/L BPA and higher doses...
December 16, 2017: Food and Chemical Toxicology
Maria Wielsøe, Christian Bjerregaard-Olesen, Peder Kern, Eva Cecilie Bonefeld-Jørgensen
Studies on associations between persistent organic pollutants (POPs) and breast cancer risk are inconclusive. The majority of studies have evaluated the effect of single compounds, without considering multiple exposures to and interactions between different POPs. The present study aimed at evaluating breast cancer risk related to combined effects of serum POP mixtures on cellular receptor functions. Data on breast cancer cases (n=77) and controls (n=84) was collected among Greenlandic Inuit women. Serum mixtures of lipophilic POPs (lipPOPs), perfluoroalkyl acids (PFAAs), and dioxin-like POPs were extracted...
December 13, 2017: Endocrine-related Cancer
Miklós Poór, Afshin Zand, Lajos Szente, Beáta Lemli, Sándor Kunsági-Máté
Zearalenone (ZEN) is a mycotoxin produced by Fusarium fungi. ZEN primarily contaminates different cereals, and exerts a strong xenoestrogenic effect in animals and humans. ZEN is a fluorescent mycotoxin, although molecular interactions and microenvironmental changes significantly modify its spectral properties. During biotransformation, ZEN is converted into α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL), the toxic metabolites of ZEN, which mimick the effect of estrogen. Cyclodextrins (CDs) are host molecules, and have been studied extensively; they can form stable complexes with several mycotoxins, including ZEN...
November 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Peter Thomas
An essential role for GPER (formerly known as GPR30) in regulating mammalian reproduction has not been identified to date, although it has shown to be involved in the regulation a broad range of other estrogen-dependent functions. In contrast, an important reproductive role for GPER in the maintenance of oocyte meiotic arrest has been identified in teleost fishes, which is briefly reviewed here. Recent studies have clearly shown that ovarian follicle production of estradiol-17β (E2 ) maintains meiotic arrest in several teleost species through activation of GPER coupled to a stimulatory G protein (Gs ) on oocyte plasma membranes, resulting in stimulation of cAMP production and maintenance of elevated cAMP levels...
February 2018: Journal of Steroid Biochemistry and Molecular Biology
Thomas W K Fraser, Abdolrahman Khezri, Anna M Lewandowska-Sabat, Theodore Henry, Erik Ropstad
Larval zebrafish (Danio rerio) are a tool for assessing endocrine disruption during early development. Here, we investigated the extent to which a simple light/dark behavioral test at five days post fertilization could compliment current methods within the field. We exposed fertilized embryos to hormones (17β-estradiol, testosterone, dihydrotestosterone, 11-ketotestosterone, thyroxine, triiodothyronine, progesterone, and hydrocortisone) and other relevant compounds (17α ethinylestradiol, bisphenol A, bisphenol S, nonylphenol, flutamide, nilutamide, linuron, drospirenone, potassium perchlorate, mifepristone, and fadrozole) to screen for behavioral effects between 96 and 118h post fertilization (hpf)...
December 2017: Aquatic Toxicology
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