scholarly journals To Cull or Not To Cull? Considerations for Studies of Endocrine-Disrupting Chemicals

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2586-2594 ◽  
Author(s):  
Alexander Suvorov ◽  
Laura N. Vandenberg
Keyword(s):  
Laboratory Animal ◽  
Animal Studies ◽  
Metabolic Diseases ◽  
Endocrine Disrupting Chemicals ◽  
Animal Experiments ◽  
Postnatal Growth ◽  
Increased Risk ◽  
Wide Range ◽  
Endocrine Disrupting ◽  
Health Related

The power of animal models is derived from the ability to control experimental variables so that observed effects may be unequivocally attributed to the factor that was changed. One variable that is difficult to control in animal experiments is the number and composition of offspring in a litter. To account for this variability, artificial equalization of the number of offspring in a litter (culling) is often used. The rationale for culling, however, has always been controversial. The Developmental Origins of Health and Disease concept provides a new context to evaluate the pros and cons of culling in laboratory animal studies, especially in the context of endocrine-disrupting chemicals. Emerging evidence indicates that culling, especially of large litters, can drastically change the feeding status of a pup, which can result in compensatory growth with long-term consequences for the animal, including increased risk of cardio-metabolic diseases. Similarly, culling of litters to intentionally bias sex ratios can alter the animal's behavior and physiology, with effects observed on a wide range of outcomes. Thus, in an attempt to control for variability in developmental rates, culling introduces an uncontrolled or confounding variable, which itself may affect a broad spectrum of health-related consequences. Variabilities in culling protocols could be responsible for differences in responses to endocrine-disrupting chemicals reported across studies. Because litter sex composition and size are vectors that can influence both prenatal and postnatal growth, they are essential considerations for the interpretation of results from laboratory animal studies.

scholarly journals Endocrine Disrupting Chemicals and Thyroid Cancer: An Overview

Toxics ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 14
Author(s):  
Mathilda Alsen ◽  
Catherine Sinclair ◽  
Peter Cooke ◽  
Kimia Ziadkhanpour ◽  
Eric Genden ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Flame Retardants ◽  
Endocrine Disrupting Chemicals ◽  
National Institutes Of Health ◽  
Future Research ◽  
National Library ◽  
Comprehensive Overview ◽  
Carcinogenic Effect ◽  
Increased Risk ◽  
Endocrine Disrupting

Endocrine disruptive chemicals (EDC) are known to alter thyroid function and have been associated with increased risk of certain cancers. The present study aims to provide a comprehensive overview of available studies on the association between EDC exposure and thyroid cancer. Relevant studies were identified via a literature search in the National Library of Medicine and National Institutes of Health PubMed as well as a review of reference lists of all retrieved articles and of previously published relevant reviews. Overall, the current literature suggests that exposure to certain congeners of flame retardants, polychlorinated biphenyls (PCBs), and phthalates as well as certain pesticides may potentially be associated with an increased risk of thyroid cancer. However, future research is urgently needed to evaluate the different EDCs and their potential carcinogenic effect on the thyroid gland in humans as most EDCs have been studied sporadically and results are not consistent.

scholarly journals The Use and Misuse of Historical Controls in Regulatory Toxicology: Lessons from the CLARITY-BPA Study

Endocrinology ◽  
2019 ◽  
Vol 161 (5) ◽  
Author(s):  
Laura N Vandenberg ◽  
Gail S Prins ◽  
Heather B Patisaul ◽  
R Thomas Zoeller
Keyword(s):  
Drug Administration ◽  
Animal Studies ◽  
Ethinyl Estradiol ◽  
Food And Drug Administration ◽  
Endocrine Disrupting Chemicals ◽  
Pituitary Neoplasms ◽  
Control Data ◽  
Endocrine Disrupting ◽  
The Us ◽  
Historical Controls

Abstract For many endocrine-disrupting chemicals (EDCs) including Bisphenol A (BPA), animal studies show that environmentally relevant exposures cause harm; human studies are consistent with these findings. Yet, regulatory agencies charged with protecting public health continue to conclude that human exposures to these EDCs pose no risk. One reason for the disconnect between the scientific consensus on EDCs in the endocrinology community and the failure to act in the regulatory community is the dependence of the latter on so-called “guideline studies” to evaluate hazards, and the inability to incorporate independent scientific studies in risk assessment. The Consortium Linking Academic and Regulatory Insights on Toxicity (CLARITY) study was intended to bridge this gap, combining a “guideline” study with independent hypothesis-driven studies designed to be more appropriate to evaluate EDCs. Here we examined an aspect of “guideline” studies, the use of so-called “historical controls,” which are essentially control data borrowed from prior studies to aid in the interpretation of current findings. The US Food and Drug Administration authors used historical controls to question the plausibility of statistically significant BPA-related effects in the CLARITY study. We examined the use of historical controls on 5 outcomes in the CLARITY “guideline” study: mammary neoplasms, pituitary neoplasms, kidney nephropathy, prostate inflammation and adenomas, and body weight. Using US Food and Drug Administration–proposed historical control data, our evaluation revealed that endpoints used in “guideline” studies are not as reproducible as previously held. Combined with other data comparing the effects of ethinyl estradiol in 2 “guideline” studies including CLARITY-BPA, we conclude that near-exclusive reliance on “guideline” studies can result in scientifically invalid conclusions.

scholarly journals Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

2020 ◽  
Vol 9 (10) ◽  
pp. 3296
Author(s):  
Aeman Zahra ◽  
Cristina Sisu ◽  
Elisabete Silva ◽  
Sophie-Christine De Aguiar Greca ◽  
Harpal S. Randeva ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Endocrine Disrupting Chemicals ◽  
Angiotensin Converting Enzyme 2 ◽  
Endocrine Disrupting ◽  
Membrane Bound ◽  
Transmembrane Serine Protease ◽  
G Protein Coupled

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.

scholarly journals PDA-cross-linked beta-cyclodextrin: a novel adsorbent for the removal of BPA and cationic dyes

2020 ◽  
Author(s):  
Jianyu Wang ◽  
Guang Cheng ◽  
Jian Lu ◽  
Huafeng Chen ◽  
Yanbo Zhou
Keyword(s):  
Endocrine Disrupting Chemicals ◽  
Inorganic Ions ◽  
Neutral Red ◽  
Carboxyl Groups ◽  
Stacking Interactions ◽  
Beta Cyclodextrin ◽  
Adsorption Capacities ◽  
Wide Range ◽  
Endocrine Disrupting ◽  
Adsorption Processes

Abstract In this study, 4,4′-(hexafluoroisopropene) diphthalic acid (PDA)-CD polymers containing β-cyclodextrin (CD) were synthesized for the adsorption of endocrine disrupting chemicals (EDCs) and dyes. It features great adsorption of bisphenol A (BPA), methylene blue (MB) and neutral red (NR). The maximum adsorption capacities of MB, NR and BPA can reach 113.06, 106.8 and 51.74 mg/g, respectively. The tandem adsorption results revealed that adsorptions of dyes and BPA onto PDA-CD polymer were two independent processes: non-polar BPA entrapment by cyclodextrin cavities while dyes were captured by the carboxyl groups and π-π stacking interactions. The adsorption processes performed well in a wide range of pH (4.0–10.0) and were not affected by fulvic acid (FA) and inorganic ions.

Gestational Exposure to Common Endocrine Disrupting Chemicals and Their Impact on Neurodevelopment and Behavior

2020 ◽  
Vol 82 (1) ◽  
pp. 177-202 ◽  
Author(s):  
Dinushan Nesan ◽  
Deborah M. Kurrasch
Keyword(s):  
Endocrine Disruption ◽  
Polybrominated Diphenyl Ethers ◽  
Animal Studies ◽  
Endocrine Disrupting Chemicals ◽  
Lactational Exposure ◽  
Gestational Exposure ◽  
Early Life Exposure ◽  
Endocrine Disrupting ◽  
Physiological Homeostasis ◽  
Nervous System Function

Endocrine disrupting chemicals are common in our environment and act on hormone systems and signaling pathways to alter physiological homeostasis. Gestational exposure can disrupt developmental programs, permanently altering tissues with impacts lasting into adulthood. The brain is a critical target for developmental endocrine disruption, resulting in altered neuroendocrine control of hormonal signaling, altered neurotransmitter control of nervous system function, and fundamental changes in behaviors such as learning, memory, and social interactions. Human cohort studies reveal correlations between maternal/fetal exposure to endocrine disruptors and incidence of neurodevelopmental disorders. Here, we summarize the major literature findings of endocrine disruption of neurodevelopment and concomitant changes in behavior by four major endocrine disruptor classes:bisphenol A, polychlorinated biphenyls, organophosphates, and polybrominated diphenyl ethers. We specifically review studies of gestational and/or lactational exposure to understand the effects of early life exposure to these compounds and summarize animal studies that help explain human correlative data.

scholarly journals Paternal Occupational Exposure to Endocrine-Disrupting Chemicals as a Risk Factor for Leukaemia in Children: A Case-Control Study from the North of England

2014 ◽  
Vol 2014 ◽  
pp. 1-7
Author(s):  
Mark S. Pearce ◽  
Lucy R. Baxter ◽  
Louise Parker
Keyword(s):  
Occupational Exposure ◽  
Case Control Study ◽  
Endocrine Disrupting Chemicals ◽  
Control Group ◽  
Live Births ◽  
The North ◽  
Increased Risk ◽  
Endocrine Disrupting ◽  
Control Study ◽  
Polychlorinated Organic Compounds

Occupations with exposures to a variety of chemicals, including those thought to be potential endocrine disruptors, have been associated with an increased risk of leukaemia in offspring. We investigated whether an association exists between paternal occupations at birth involving such exposures and risk of leukaemia in offspring. Cases (n=958) were matched, on sex and year of birth, to controls from two independent sources, one other cancers, one cancer-free live births. Paternal occupations at birth were classified, using an occupational exposure matrix, as having “very unlikely,” “possible,” or “likely” exposure to six groups of potential endocrine-disrupting chemicals. There was a significantly increased risk of acute nonlymphocytic leukaemia (ANLL) for polychlorinated organic compounds (OR 1.95, 95% CI 1.08–3.54) only in comparison with cancer-free controls, and for phthalates (OR 1.61, 95% CI 1.00–2.61) only with registry controls. A number of other, including inverse, associations were seen, but limited to one control group only. No associations were seen with likely paternal exposure to heavy metals. The associations identified in this study require further investigation, with better exposure and potential confounding (for example maternal variables) information, to evaluate the likelihood of true associations to assess whether they are real or due to chance.

scholarly journals The Interplay between Immune System and Microbiota in Osteoporosis

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Pietro Locantore ◽  
Valeria Del Gatto ◽  
Silvia Gelli ◽  
Rosa Maria Paragliola ◽  
Alfredo Pontecorvi
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Bone Cells ◽  
Bone Microarchitecture ◽  
Interleukin 17 ◽  
Mineral Density ◽  
Increased Risk ◽  
Long Term Treatment ◽  
Wide Range

Osteoporosis is a disease characterized by low bone mass and alterations of bone microarchitecture, with an increased risk of fractures. It is a multifactorial disorder that is more frequent in postmenopausal women but can be associated to other diseases (inflammatory and metabolic diseases). At present, several options are available to treat osteoporosis trying to block bone reabsorption and reduce the risk of fracture. Anyway, these drugs have safety and tolerance problems in long-term treatment. Recently, gut microbiota has been highlighted to have strong influence on bone metabolism, becoming a potential new target to modify bone mineral density. Such evidences are mainly based on mouse models, showing an involvement in modulating the interaction between the immune system and bone cells. Germ-free mice represent a basic model to understand the interaction between microbiota, immune system, and bone cells, even though data are controversial. Anyway, such models have unequivocally demonstrated a connection between such systems, even if the mechanism is unclear. Gut microbiota is a complex system that influences calcium and vitamin D absorption and modulates gut permeability, hormonal secretion, and immune response. A key role is played by the T helper 17 lymphocytes, TNF, interleukin 17, and RANK ligand system. Other important pathways include NOD1, NOD2, and Toll-like receptor 5. Prebiotics and probiotics are a wide range of substances and germs that can influence and modify microbiota. Several studies demonstrated actions by different prebiotics and probiotics in different animals, differing according to sex, age, and hormonal status. Data on the effects on humans are poor and controversial. Gut microbiota manipulation appears a possible strategy to prevent and treat osteopenia and/or osteoporosis as well as other possible bone alterations, even though further clinical studies are necessary to identify correct procedures in humans.

scholarly journals Environmental Obesogens and Human Health

2021 ◽  
Author(s):  
Archisman Mahapatra ◽  
Priya Gupta ◽  
Anjali Suman ◽  
Rahul Kumar Singh
Keyword(s):  
Human Health ◽  
Endocrine Disruption ◽  
Adult Population ◽  
Endocrine Disrupting Chemicals ◽  
Model Systems ◽  
Health Concern ◽  
Increased Risk ◽  
Endocrine Disrupting ◽  
The World ◽  
Underlying Mechanisms

Obesity is an alarming public health concern that contributes to a substantially increased risk of multiple chronic disorders, including diabetes. As per WHO data, in 2016, almost 39% adult population of the world is overweight, 13% of them were obese. There is prominent evidence on the involvement of environmental endocrine-disrupting chemicals, termed obesogens, in the prevalence of this growing worldwide pandemic, obesity. The exaggerated effect of obesogens on endocrine disruption, lipid metabolism and homeostasis, adipocyte functioning, impaired thermogenesis, inflammation, epigenetics, and overall human health will be covered in this chapter. This chapter will discuss the environmental obesogen hypothesis, the epidemiological and experimental evidence of obesogens, its chemical characteristics, and possible mechanism of actions. It will also focus on some recent indications of obesogens and their correlation in COVID-19 disease pathogenesis. This chapter will try to conclude with strategies for identifying the underlying mechanisms of obesogens within model systems and the human body, including future directions.

scholarly journals Does the claustrum have a function? Lessons from human lesion and animal studies point to divergent multifunctionality

2021 ◽  
Author(s):  
Huriye Atilgan ◽  
Max Doody ◽  
David K Oliver ◽  
Thomas M McGrath ◽  
Andrew M Shelton ◽  
...  
Keyword(s):  
Animal Studies ◽  
Animal Experiments ◽  
Experimental Studies ◽  
Signs And Symptoms ◽  
Global Function ◽  
Motor Abilities ◽  
Neural Processes ◽  
Wide Range ◽  
Functional Implications ◽  
Lesion Studies

The claustrum is the most densely interconnected region in the human brain. Despite the accumulating data from clinical and experimental studies, the functional role(s) of the claustrum remain unknown. Here, we systematically review claustrum lesion studies and discuss their functional implications. Claustral lesions are associated with an array of signs and symptoms, including changes in cognitive, perceptual and motor abilities; electrical activity; mental state; and sleep. The wide range of symptoms observed following claustral lesions suggests that the claustrum may either have a number of distinct functions, or a global function that impacts many neural processes. We further discuss the implications of these lesions in the context of recent evidence linking the claustrum to sensory perception, sleep, and salience as well as highlighting an underexplored link between the claustrum and pain. We hypothesize that the claustrum is connected to multiple brain networks, both ancient and advanced, which underly fundamental functions as well as higher cognitive processes. Extensive evidence derived from human lesion studies and animal experiments provides unequivocal evidence for a key function of the claustrum as a multifunctional node in numerous networks.

scholarly journals The Impact of Endocrine-Disrupting Chemicals on Female Fertility

2020 ◽  
Vol 71 (6) ◽  
pp. 286-294
Author(s):  
Aida Petca ◽  
Nicoleta Maru ◽  
Mihai Cristian Dumitrascu ◽  
Madalina Sighencea ◽  
Florica Sandru ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Polycystic Ovary ◽  
Endocrine Disrupting Chemicals ◽  
Antral Follicle ◽  
Lower Probability ◽  
Vitro Fertilization ◽  
Increased Risk ◽  
Endocrine Disrupting ◽  
The Impact

Nowadays, infertility is a prevalent problem among couples. Exposure to endocrine-disrupting chemicals (EDCs) may influence the female reproductive outcomes through multiple mechanisms, being one of the important causes of infertility. These compounds may interfere with some fertility and fecundity markers, leading to increased time to pregnancy, increased risk of spontaneous abortion, shorter menstrual cycles, early age at menopause, anovulation or delayed ovulation, smaller preovulatory follicles, increased serum FSH, decreased synthesis of estradiol and progesterone, low plasma levels of anti-Mullerian hormone and decreased antral follicle count. Endocrine-disrupting chemicals may also impair in vitro fertilization outcomes, being responsible for: a lower probability of implantation, reduced fertilization rates, diminished probability of clinical pregnancy, and near term pregnancies after in vitro fertilization. Another mechanism of altering the female reproductive function is through the disorders induced by EDCs, such as polycystic ovary syndrome, uterine fibroids, and endometriosis. Those conditions may finally lead to infertility.

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