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 Endocrine disruption of the epigenome: a breast cancer link

2014 ◽  
Vol 21 (2) ◽  
pp. T33-T55 ◽  
Author(s):  
Kevin C Knower ◽  
Sarah Q To ◽  
Yuet-Kin Leung ◽  
Shuk-Mei Ho ◽  
Colin D Clyne
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Endocrine Disruption ◽  
Endocrine Disrupting Chemicals ◽  
Experimental Models ◽  
Epigenetic Alterations ◽  
Early Life Exposure ◽  
Endocrine Disrupting ◽  
Heterogenous Population

The heritable component of breast cancer accounts for only a small proportion of total incidences. Environmental and lifestyle factors are therefore considered to among the major influencing components increasing breast cancer risk. Endocrine-disrupting chemicals (EDCs) are ubiquitous in the environment. The estrogenic property of EDCs has thus shown many associations between ongoing exposures and the development of endocrine-related diseases, including breast cancer. The environment consists of a heterogenous population of EDCs and despite many identified modes of action, including that of altering the epigenome, drawing definitive correlations regarding breast cancer has been a point of much discussion. In this review, we describe in detail well-characterized EDCs and their actions in the environment, their ability to disrupt mammary gland formation in animal and human experimental models and their associations with exposure and breast cancer risk. We also highlight the susceptibility of early-life exposure to each EDC to mediate epigenetic alterations, and where possible describe how these epigenome changes influence breast cancer risk.

scholarly journals Epigenetics, Evolution, Endocrine Disruption, Health, and Disease

Endocrinology ◽  
2006 ◽  
Vol 147 (6) ◽  
pp. s4-s10 ◽  
Author(s):  
David Crews ◽  
John A. McLachlan
Keyword(s):  
Mental Health ◽  
Recent Work ◽  
Endocrine Disruption ◽  
Endocrine Disrupting Chemicals ◽  
Epigenetic Mechanisms ◽  
Physical And Mental Health ◽  
Risk Levels ◽  
Endocrine Disrupting ◽  
Increase Risk ◽  
Health And Disease

Abstract Endocrine-disrupting chemicals (EDCs) in the environment have been linked to human health and disease. This is particularly evident in compounds that mimic the effects of estrogens. Exposure to EDCs early in life can increase risk levels of compromised physical and mental health. Epigenetic mechanisms have been implicated in this process. Transgenerational consequences of EDC exposure is also discussed in both a proximate (mechanism) and ultimate (evolution) context as well as recent work suggesting how such transmission might become incorporated into the genome and subject to selection. We suggest a perspective for exploring and ultimately coming to understand diseases that may have environmental or endocrine origins.

scholarly journals Developmental Exposure to Endocrine Disrupting Chemicals and Its Impact on Cardio-Metabolic-Renal Health

2021 ◽  
Vol 3 ◽  
Author(s):  
Radha Dutt Singh ◽  
Kavita Koshta ◽  
Ratnakar Tiwari ◽  
Hafizurrahman Khan ◽  
Vineeta Sharma ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Energy Homeostasis ◽  
Endocrine Disrupting Chemicals ◽  
Developmental Exposure ◽  
Adverse Health Outcomes ◽  
Early Life Exposure ◽  
Endocrine Disrupting ◽  
Similar Mode ◽  
Health And Disease ◽  
Hormone System

Developmental origin of health and disease postulates that the footprints of early life exposure are followed as an endowment of risk for adult diseases. Epidemiological and experimental evidence suggest that an adverse fetal environment can affect the health of offspring throughout their lifetime. Exposure to endocrine disrupting chemicals (EDCs) during fetal development can affect the hormone system homeostasis, resulting in a broad spectrum of adverse health outcomes. In the present review, we have described the effect of prenatal EDCs exposure on cardio-metabolic-renal health, using the available epidemiological and experimental evidence. We also discuss the potential mechanisms of their action, which include epigenetic changes, hormonal imprinting, loss of energy homeostasis, and metabolic perturbations. The effect of prenatal EDCs exposure on cardio-metabolic-renal health, which is a complex condition of an altered biological landscape, can be further examined in the case of other environmental stressors with a similar mode of action.

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.

Engaging Undergraduates in the Scientific Process: Exploring Invertebrate Endocrine Disruption

2016 ◽  
Vol 78 (5) ◽  
pp. 410-416 ◽  
Author(s):  
Scott Layton ◽  
Jason Belden
Keyword(s):  
Endocrine Disruption ◽  
Endocrine Disrupting Chemicals ◽  
Model Organism ◽  
Female Offspring ◽  
Reproduction Rate ◽  
Interest In Science ◽  
Endocrine Disrupting ◽  
Set Up ◽  
Reproductive Study ◽  
Analyze Data

Engaging students in the process of science to increase learning and critical thinking has become a key emphasis in undergraduate education. Introducing environmental topics, such as the effects of endocrine-disrupting chemicals, into undergraduate courses offers a new means to increase student engagement. Daphnia magna can serve as a model organism for endocrine disruption, and its ease of handling, rapid reproduction rate, and clearly defined endpoints make it useful in short-term, student research projects. The concept of endocrine disruption can be tested through a 21-day reproductive study of D. magna exposed to varying concentrations of the pesticide fenoxycarb. Students will observe an altered reproduction rate and increased production of males under conditions that would typically result only in the production of female offspring. This research system allows students to formulate hypotheses, set up experiments, analyze data, and present results, leading to a greater appreciation of and interest in science.

scholarly journals Hormone-Activated Estrogen Receptors in Annelid Invertebrates: Implications for Evolution and Endocrine Disruption

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1731-1738 ◽  
Author(s):  
June Keay ◽  
Joseph W. Thornton
Keyword(s):  
Estrogen Receptors ◽  
Endocrine Disruption ◽  
Endocrine Disrupting Chemicals ◽  
Estrogen Signaling ◽  
Estrogen Sensitivity ◽  
Endocrine Disrupting ◽  
Platynereis Dumerilii ◽  
Bilaterian Animal ◽  
Capitella Capitata ◽  
And Behavior

As the primary mediators of estrogen signaling in vertebrates, estrogen receptors (ERs) play crucial roles in reproduction, development, and behavior. They are also the major mediators of endocrine disruption by xenobiotic pollutants that mimic or block estrogen action. ERs that are sensitive to estrogen and endocrine disrupters have long been thought to be restricted to vertebrates: although there is evidence for estrogen signaling in invertebrates, the only ERs studied to date, from mollusks and cephalochordates, have been insensitive to estrogen and therefore incapable of mediating estrogen signaling or disruption. To determine whether estrogen sensitivity is ancestral or a unique characteristic of vertebrate ERs, we isolated and characterized ERs from two annelids, Platynereis dumerilii and Capitella capitata, because annelids are the sister phylum to mollusks and have been shown to produce and respond to estrogens. Functional assays show that annelid ERs specifically activate transcription in response to low estrogen concentrations and bind estrogen with high affinity. Furthermore, numerous known endocrine-disrupting chemicals activate or antagonize the annelid ER. This is the first report of a hormone-activated invertebrate ER. Our results indicate that estrogen signaling via the ER is as ancient as the ancestral bilaterian animal and corroborate the estrogen sensitivity of the ancestral steroid receptor. They suggest that the taxonomic scope of endocrine disruption by xenoestrogens may be very broad and reveal how functional diversity evolved in a gene family central to animal endocrinology.

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