Endocrine-disrupting actions of PCBs on brain development and social and reproductive behaviors

Bell, Margaret R.

doi:10.1016/j.coph.2014.09.020

Cited by 72 publications

(53 citation statements)

References 101 publications

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“…Although their production in the United States was banned in the 1970s and their use today is highly controlled, PCBs persist in the environment and accumulate in the food web (Bell 2014; Fernandez-Gonzalez et al 2015). Different PCB congeners have been associated with reproductive dysfunction in females.…”

Section: Polychlorinated Biphenylsmentioning

confidence: 99%

Exposure to endocrine disruptors during adulthood: consequences for female fertility

Rattan

Zhou

Chiang

et al. 2017

Journal of Endocrinology

257

150

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Endocrine disrupting chemicals are ubiquitous chemicals that exhibit endocrine disrupting properties in both humans and animals. Female reproduction is an important process, which is regulated by hormones and is susceptible to the effects of exposure to endocrine disrupting chemicals. Disruptions in female reproductive functions by endocrine disrupting chemicals may result in subfertility, infertility, improper hormone production, estrous and menstrual cycle abnormalities, anovulation, and early reproductive senescence. This review summarizes the effects of a variety of synthetic endocrine disrupting chemicals during adult life. The chemicals covered in this review are pesticides (organochlorines, organophosphates, carbamates, pyrethroids, and triazines), heavy metals (arsenic, lead, and mercury), diethylstilbesterol, plasticizer alternatives (di-(2-ethylhexyl) phthalate and bisphenol A alternatives), 2,3,7,8-tetrachlorodibenzo-p-dioxin, nonylphenol, polychlorinated biphenyls, triclosan, and parabens. This review focuses on the hypothalamus, pituitary, ovary, and uterus because together they regulate normal female fertility and the onset of reproductive senescence. The literature shows that several endocrine disrupting chemicals have endocrine disrupting abilities in females during adult life, causing fertility abnormalities in both humans and animals.

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Section: Polychlorinated Biphenylsmentioning

confidence: 99%

Exposure to endocrine disruptors during adulthood: consequences for female fertility

Rattan

Zhou

Chiang

et al. 2017

Journal of Endocrinology

257

150

View full text Add to dashboard Cite

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“…Numerous studies have demonstrated a relationship between PCBs exposure and a variety of toxic effects, such as carcinogenicity, teratogenicity or reproductive toxicology in animals (Bell, 2014;El Majidi et al, 2014;Zani et al, 2013). Also, correlation between environmental and occupational exposures to PCBs and human prostate cancer has been reported (Kling et al, 1978;Hessel et al, 2004).…”

Section: Introductionmentioning

confidence: 96%

Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

Bedia

Dalmau

Jaumot

et al. 2015

Environmental Research

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Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT induction (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs.

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“…Numerous modes of action have been described that may contribute to neurotoxicity. This includes altered neurotransmitter signaling (Fonnum and Mariussen, 2009;Mariussen and Fonnum, 2001;Wigestrand et al, 2013), altered GABA A receptor activity (Fernandes et al, 2010), altered Ca 2þ homeostasis through several mechanisms (Choi et al, 2016;Gafni et al, 2004;Kodavanti and Tilson, 1997;Pessah et al, 2010;Westerink, 2014), induced reactive oxygen species (Stenberg et al, 2011), altered cell viability (Dickerson et al, 2009), and alterations of neuro/endocrine processes (Bell, 2014;Fonnum and Mariussen, 2009;Kodavanti and Curras-Collazo, 2010). Of the modes identified, a particularly sensitive endpoint is the ability of NDL PCBs to enhance the activity of ryanodine sensitive Ca 2þ channels embedded in the sarco/endoplasmic reticulum (SR/ER), namely, the ryanodine receptor (RyR), in both mammals (Pessah et al, 2006) and fish (Fritsch and Pessah, 2013).…”

mentioning

confidence: 99%

An Extended Structure–Activity Relationship of Nondioxin-Like PCBs Evaluates and Supports Modeling Predictions and Identifies Picomolar Potency of PCB 202 Towards Ryanodine Receptors

et al. 2016

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Nondioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine-sensitive Ca 2þ channels (RyRs) and this activation has been associated with neurotoxicity in exposed animals. RyR-active congeners follow a distinct structure-activity relationship and a quantitative structure-activity relationship (QSAR) predicts that a large number of PCBs likely activate the receptor, which requires validation. Additionally, previous structural based conclusions have been established using receptor ligand binding assays but the impact of varying PCB structures on ion channel gating behavior is not understood. We used [ 3 H]Ryanodine ([ 3 H]Ry) binding to assess the RyR-activity of 14 previously untested PCB congeners evaluating the predictability of the QSAR. Congeners determined to display widely varying potency were then assayed with single channel voltage clamp analysis to assess direct influences on channel gating kinetics. The RyR-activity of individual PCBs assessed in in vitro assays followed the general pattern predicted by the QSAR but binding and lipid bilayer experiments demonstrated higher potency than predicted. Of the 49 congeners tested to date, tetra-ortho PCB 202 was found to be the most potent RyR-active congener increasing channel open probability at 200 pM. Shifting meta-substitutions to the paraposition resulted in a > 100-fold reduction in potency as seen with PCB 197. Non-ortho PCB 11 was found to lack activity at the receptor supporting a minimum mono-ortho substitution for PCB RyR activity. These findings expand and support previous SAR assessments; where out of the 49 congeners tested to date 42 activate the receptor demonstrating that the RyR is a sensitive and common target of PCBs.

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Endocrine-disrupting actions of PCBs on brain development and social and reproductive behaviors

Cited by 72 publications

References 101 publications

Exposure to endocrine disruptors during adulthood: consequences for female fertility

Exposure to endocrine disruptors during adulthood: consequences for female fertility

Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

An Extended Structure–Activity Relationship of Nondioxin-Like PCBs Evaluates and Supports Modeling Predictions and Identifies Picomolar Potency of PCB 202 Towards Ryanodine Receptors

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