scholarly journals From Cohorts to Molecules: Adverse Impacts of Endocrine Disrupting Mixtures

2017 ◽  
Author(s):  
Lina Birgersson ◽  
Gábor Borbély ◽  
Nicolò Caporale ◽  
Pierre-Luc Germain ◽  
Michelle Leemans ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Endocrine Disrupting Chemicals ◽  
Experimental Studies ◽  
Real Life ◽  
Epidemiological Data ◽  
Model Organisms ◽  
Simultaneous Exposure ◽  
Endocrine Disrupting

ABSTRACTConvergent evidence associates endocrine disrupting chemicals (EDCs) with major, increasingly-prevalent human disorders. Regulation requires elucidation of EDC-triggered molecular events causally linked to adverse health outcomes, but two factors limit their identification. First, experiments frequently use individual chemicals, whereas real life entails simultaneous exposure to multiple EDCs. Second, population-based and experimental studies are seldom integrated. This drawback was exacerbated until recently by lack of physiopathologically meaningful human experimental systems that link epidemiological data with results from model organisms.We developed a novel approach, integrating epidemiological with experimental evidence. Starting from 1,874 mother-child pairs we identified mixtures of chemicals, measured during early pregnancy, associated with language delay or low-birth weight in offspring. These mixtures were then tested on multiple complementary in vitro and in vivo models. We demonstrate that each EDC mixture, at levels found in pregnant women, disrupts hormone-regulated and disease-relevant gene regulatory networks at both the cellular and organismal scale.

scholarly journals Assessment and Molecular Actions of Endocrine-Disrupting Chemicals That Interfere with Estrogen Receptor Pathways

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Gwenneg Kerdivel ◽  
Denis Habauzit ◽  
Farzad Pakdel
Keyword(s):  
Synergistic Effects ◽  
Animal Health ◽  
Endocrine Disrupting Chemicals ◽  
Estrogen Signaling ◽  
Synthetic Chemicals ◽  
Endocrine Disrupting ◽  
And Function ◽  
Analytical Tools

In all vertebrate species, estrogens play a crucial role in the development, growth, and function of reproductive and nonreproductive tissues. A large number of natural or synthetic chemicals present in the environment and diet can interfere with estrogen signaling; these chemicals are called endocrine disrupting chemicals (EDCs) or xenoestrogens. Some of these compounds have been shown to induce adverse effects on human and animal health, and some compounds are suspected to contribute to diverse disease development. Because xenoestrogens have varying sources and structures and could act in additive or synergistic effects when combined, they have multiple mechanisms of action. Consequently, an important panel ofin vivoandin vitrobioassays and chemical analytical tools was used to screen, evaluate, and characterize the potential impacts of these compounds on humans and animals. In this paper, we discuss different molecular actions of some of the major xenoestrogens found in food or the environment, and we summarize the current models used to evaluate environmental estrogens.

scholarly journals Membrane filtration in water recycling: removal of natural hormones

2003 ◽  
Vol 3 (3) ◽  
pp. 155-160 ◽  
Author(s):  
L.D. Nghiem ◽  
A.I. Schäfer ◽  
T.D. Waite
Keyword(s):  
Membrane Filtration ◽  
Endocrine Disrupting Chemicals ◽  
In Vivo Studies ◽  
Water Recycling ◽  
Endocrine Disrupting ◽  
Adsorptive Behavior ◽  
Stirred Cell ◽  
Natural Hormones

Recent detections of endocrine-disrupting chemicals (EDCs) in effluent are of great concern to sections of the community associated with the issue of water recycling. In vitro and in vivo studies by many researchers have confirmed the impacts of EDCs on trout at the common concentration encountered in sewage effluent. Amongst many types of EDCs the impacts of steroid estrogens such as estrone, estradiol (natural hormones) and ethinylestradiol (a synthetic hormone) are prominent as they have far higher endocrine-disrupting potency than other synthetic EDCs. Given the continuous developments in membrane technology, tertiary treatment using membrane processes has been identified as a promising technology to provide a safeguard to water recycling practice and to protect the environment. This paper investigates retention and adsorptive behavior of the natural hormones estrone and estradiol by two commercial low-pressure nanofiltration membranes TFC-SR2 and TFC-S, using dead end stirred cell systems. The removal phenomena of estradiol are similar to that of estrone. pH has been found to significantly influence the adsorption of estrone and estradiol by the membranes, presumably due to hydrogen bonding. This adsorption is critical in the risk of possible release of such hormones to the product waters. Total adsorbed amounts were calculated for standard membrane elements and are indeed important.

In vivo and in vitro Screening of Endocrine Disrupting Chemicals with Estrogenic activity in Japanese Quail

2005 ◽  
Vol 16 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Kiyoshi Shimada ◽  
Yonju Ha ◽  
Akira Tsukada ◽  
Noboru Saito ◽  
Shinobu Maekawa ◽  
...  
Keyword(s):  
Japanese Quail ◽  
Estrogenic Activity ◽  
Endocrine Disrupting Chemicals ◽  
Endocrine Disrupting

Endocrine potency of wastewater: Contents of endocrine disrupting chemicals and effects measured by in vivo and in vitro assays

2010 ◽  
Vol 30 (2) ◽  
pp. 413-426 ◽  
Author(s):  
Kresten Ole Kusk ◽  
Tanja Krüger ◽  
Manhai Long ◽  
Camilla Taxvig ◽  
Anne E. Lykkesfeldt ◽  
...  
Keyword(s):  
Endocrine Disrupting Chemicals ◽  
In Vitro Assays ◽  
Endocrine Disrupting

scholarly journals The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds

2020 ◽  
Vol 21 (10) ◽  
pp. 3480 ◽  
Author(s):  
Juliette Legler ◽  
Daniel Zalko ◽  
Fabien Jourdan ◽  
Miriam Jacobs ◽  
Bernard Fromenty ◽  
...  
Keyword(s):  
Endocrine Disrupting Chemicals ◽  
Real Life ◽  
Integrated Approach ◽  
Test Method ◽  
Adverse Outcome Pathway ◽  
In Vivo Models ◽  
Project Report ◽  
Metabolic Disruption

The purpose of this project report is to introduce the European “GOLIATH” project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as “metabolism disrupting compounds” (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world’s first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption—hepatocytes, pancreatic endocrine cells, myocytes and adipocytes—and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development.

scholarly journals In vitro ovarian culture system provides insight into the mechanism underlying follicle assembly in vivo

Development ◽  
2021 ◽  
pp. dev.197459
Author(s):  
Ren Tanimoto ◽  
Kiyono Sekii ◽  
Kanako Morohaku ◽  
Jianzhen Li ◽  
David Pepin ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Endocrine Disrupting Chemicals ◽  
Ectopic Expression ◽  
Perinatal Period ◽  
Primordial Follicles ◽  
Estrogen Exposure ◽  
Endocrine Disrupting ◽  
Insight Into

In mammals, primordial follicles assembled in fetuses or during infancy constitute the oocyte resources for life. Exposure to 17beta-estradiol and phytogenic or endocrine-disrupting chemicals during pregnancy and/or the perinatal period leads to the failure of normal follicle formation. However, the mechanisms underlying estrogen-mediated abnormal follicle formation and physiological follicle formation in the presence of endogenous natural estrogen are not well-understood. Here, we reveal that estrogen receptor 1, activated by estrogen, binds to the 5′ region of the anti-Mullerian hormone (Amh) gene and upregulates its transcription before follicle formation in cultured mouse fetal ovaries. Ectopic expression of AMH protein was observed in pregranulosa cells of these explants. Furthermore, AMH addition to the culture medium inhibited normal follicle formation. Conversely, alpha-fetoprotein (AFP) produced in fetal liver reportedly blocks estrogen action, although its role in follicle formation is unclear. We further demonstrated that AFP addition to the medium inhibited ectopic AMH expression via estrogen, leading to successful follicle formation in vitro. Collectively, our in vitro experiments suggest that upon estrogen exposure, the integrity of follicle assembly in vivo is ensured by AFP.

scholarly journals Obesity and Endocrine Disrupting Chemicals

2021 ◽  
Author(s):  
Angelica Amorim Amato ◽  
Hailey Britt Wheeler ◽  
Bruce Blumberg
Keyword(s):  
Physical Inactivity ◽  
Endocrine Disrupting Chemicals ◽  
Model Organisms ◽  
Noncommunicable Diseases ◽  
Current Evidence ◽  
Endocrine Disrupting Chemical ◽  
Endocrine Disrupting ◽  
Contact Exposure ◽  
Prevalence Of Obesity

Obesity is now a worldwide pandemic. The usual explanation given for the prevalence of obesity is that it results from consumption of a calorie dense diet coupled with physical inactivity. However, this model inadequately explains rising obesity in adults and in children over the past few decades, indicating that other factors must be important contributors. An Endocrine-Disrupting Chemical (EDC) is an exogenous chemical, or mixture that interferes with any aspect of hormone action. EDCs have become pervasive in our environment, allowing humans to be exposed daily through ingestion, inhalation, and direct dermal contact. Exposure to EDCs has been causally linked with obesity in model organisms and associated with obesity occurrence in humans. Obesogens are chemicals, including some EDCs that promote adipogenesis and obesity, in vivo, by a variety of mechanisms. The environmental obesogen model holds that exposure to obesogens elicits a predisposition to obesity and that such exposures may be an important yet overlooked factor in the obesity pandemic. Effects produced by EDCs and obesogen exposure may be passed to subsequent, unexposed generations. This “generational toxicology” is not currently factored into risk assessment by regulators but may be another important factor in the obesity pandemic as well as in the worldwide increases in the incidence of noncommunicable diseases that plague populations everywhere. This review addresses the current evidence on how obesogens affect body mass, discusses long-known chemicals that have been more recently identified as obesogens, and how the accumulated knowledge can help identify EDCs hazards.

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