Sex-Specific Disruption of the Prairie Vole Hypothalamus by Developmental Exposure to a Flame Retardant Mixture

Endocrinology ◽  
2021 ◽  
Author(s):  
Sagi Enicole A Gillera ◽  
William P Marinello ◽  
Kevin T Cao ◽  
Brian M Horman ◽  
Heather M Stapleton ◽  
...  
Keyword(s):  
Flame Retardants ◽  
Prairie Vole ◽  
Zona Incerta ◽  
Prairie Voles ◽  
Behavioral Deficits ◽  
Developmental Exposure ◽  
Neuronal Populations ◽  
Increased Risk ◽  
Osmotic Balance ◽  
Multiple Species

Abstract Prevalence of neurodevelopmental disorders (NDDs) with social deficits is conspicuously rising, particularly in boys. Flame retardants (FRs) have long been associated with increased risk, and prior work by us and others in multiple species has shown that developmental exposure to the common FR mixture Firemaster 550 (FM 550) sex-specifically alters socioemotional behaviors including anxiety and pair bond formation. In rats, FRs have also been shown to impair aspects of osmoregulation. Because vasopressin (AVP) plays a role in both socioemotional behavior and osmotic balance we hypothesized that AVP and its related nonapeptide oxytocin (OT) would be vulnerable to developmental FM 550 exposure. We used the prairie vole (Microtus ochrogaste) to test this because it is spontaneously prosocial. Using siblings of prairie voles used in a prior study that assessed behavioral deficits resulting from developmental FM 550 exposure across three doses, here we tested the hypothesis that FM 550 sex-specifically alters AVP and OT neuronal populations in critical nuclei, such as the paraventricular nucleus (PVN) that coordinate those behaviors, as well as related dopaminergic (determined by tyrosine hydroxylase (TH) immunolabeling) populations. Exposed females had fewer AVP neurons in the anterior PVN and more A13 TH neurons in the zona incerta compared to controls. By contrast, in FM 550 males, A13 TH neuron numbers in the zona incerta were decreased but only in one dose group. These results expand on previous work showing evidence of endocrine disruption of OT/AVP pathways, including to subpopulations of PVN AVP neurons that coordinate osmoregulatory functions in the periphery.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Morgan R. Peltier ◽  
Michael J. Fassett ◽  
Yuko Arita ◽  
Vicki Y. Chiu ◽  
Jiaxiao M. Shi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Los Angeles ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Plasma Concentrations ◽  
First Trimester ◽  
High Plasma ◽  
Thyroid Stimulating Hormone ◽  
Spontaneous Preterm Birth ◽  
Increased Risk

Abstract Objectives Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. Methods Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. Results We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. Conclusions These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

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 Developmental exposure to low concentrations of two brominated flame retardants, BDE-47 and BDE-99, causes life-long behavioral alterations in zebrafish

2018 ◽  
Vol 66 ◽  
pp. 221-232 ◽  
Author(s):  
Lilah Glazer ◽  
Corinne N. Wells ◽  
Meghan Drastal ◽  
Kathryn-Ann Odamah ◽  
Richard E. Galat ◽  
...  
Keyword(s):  
Flame Retardants ◽  
Brominated Flame Retardants ◽  
Behavioral Alterations ◽  
Developmental Exposure ◽  
Low Concentrations

scholarly journals Human Neural Stem Cells Differentiate and Integrate, Innervating Implanted zQ175 Huntington’s Disease Mouse Striatum

2021 ◽  
Author(s):  
Sandra M. Holley ◽  
Jack C. Reidling ◽  
Carlos Cepeda ◽  
Alice Lau ◽  
Cindy Moore ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Pyramidal Neurons ◽  
Neurodegenerative Disorder ◽  
Functional Integration ◽  
Behavioral Deficits ◽  
Human Neural Stem Cells ◽  
Neuronal Populations

AbstractHuntington’s disease (HD), a genetic neurodegenerative disorder, primarily impacts the striatum and cortex with progressive loss of medium-sized spiny neurons (MSNs) and pyramidal neurons, disrupting cortico-striatal circuitry. A promising regenerative therapeutic strategy of transplanting human neural stem cells (hNSCs) is challenged by the need for long-term functional integration. We previously described that hNSCs transplanted into the striatum of HD mouse models differentiated into electrophysiologically active immature neurons, improving behavior and biochemical deficits. Here we show that 8-month implantation of hNSCs into the striatum of zQ175 HD mice ameliorates behavioral deficits, increases brain-derived neurotrophic factor (BDNF) and reduces mutant Huntingtin (mHTT) accumulation. Patch clamp recordings, immunohistochemistry and electron microscopy demonstrates that hNSCs differentiate into diverse neuronal populations, including MSN- and interneuron-like cells. Remarkably, hNSCs receive synaptic inputs, innervate host neurons, and improve membrane and synaptic properties. Overall, the findings support hNSC transplantation for further evaluation and clinical development for HD.

scholarly journals Breed-related expression patterns of Ki67, γH2AX, and p21 during ageing in the canine liver

2020 ◽  
Author(s):  
Laura J. A. Hardwick ◽  
Andre J. Kortum ◽  
Fernando Constantino-Casas ◽  
Penny J. Watson
Keyword(s):  
Chronic Hepatitis ◽  
Cellular Senescence ◽  
Expression Patterns ◽  
Strongly Correlated ◽  
High Power Field ◽  
Increased Risk ◽  
Study Population ◽  
Multiple Species ◽  
Cell Proliferation Marker ◽  
Lower Expression

AbstractCellular senescence is a molecular hallmark of ageing that is associated with multiple pathologies, and DNA damage marker γH2AX, together with cell cycle inhibitor p21, have been used as senescence markers in multiple species including dogs. Idiopathic canine chronic hepatitis has recognised breed-related differences in predisposition and prognosis, but reasons behind this are poorly understood. This retrospective study using archived post mortem tissue aimed to provide insight into liver ageing in 51 microscopically normal canine livers across seven breed categories, including those with and without increased risk of chronic hepatitis. Immunohistochemistry was conducted for γH2AX, p21, and cell proliferation marker Ki67, and the mean number of positive hepatocytes per high power field was determined. All three markers were strongly correlated to each other, but no age-dependent expression was seen in the combined study population. Overall expression levels were low in most dogs, with median values representing less than 1.5% of hepatocytes, but this increased to 20–30% in individual dogs at the upper end of the range. Individual breed differences were noted in two breeds that have increased risk of chronic hepatitis, with English Springer Spaniels having lower expression of Ki67 than other dogs, and Labradors having higher expression of Ki67 and γH2AX than other dogs. These results warrant further investigation in these breeds and highlight a need to validate reliable markers of cellular senescence in dogs.

scholarly journals Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish

2018 ◽  
Vol 165 (2) ◽  
pp. 487-498 ◽  
Author(s):  
Lilah Glazer ◽  
Andrew B Hawkey ◽  
Corinne N Wells ◽  
Meghan Drastal ◽  
Kathryn-Ann Odamah ◽  
...  
Keyword(s):  
Flame Retardants ◽  
Behavioral Alterations ◽  
Developmental Exposure ◽  
Low Concentrations

Long-term pathological consequences of prenatal infection: beyond brain disorders

2015 ◽  
Vol 309 (1) ◽  
pp. R1-R12 ◽  
Author(s):  
Marie A. Labouesse ◽  
Wolfgang Langhans ◽  
Urs Meyer
Keyword(s):  
Wide Spectrum ◽  
Brain Disorders ◽  
Behavioral Deficits ◽  
Metabolic Functions ◽  
Behavioral Abnormalities ◽  
Prenatal Infection ◽  
Increased Risk ◽  
Immune Challenges ◽  
Glycemic Regulation

Prenatal immunological adversities such as maternal infection have been widely acknowledged to contribute to an increased risk of neurodevelopmental brain disorders. In recent years, epidemiological and experimental evidence has accumulated to suggest that prenatal exposure to immune challenges can also negatively affect various physiological and metabolic functions beyond those typically associated with primary defects in CNS development. These peripheral changes include excessive accumulation of adipose tissue and increased body weight, impaired glycemic regulation and insulin resistance, altered myeloid lineage development, increased gut permeability, hyperpurinergia, and changes in microbiota composition. Experimental work in animal models further suggests that at least some of these peripheral abnormalities could directly contribute to CNS dysfunctions, so that normalization of peripheral pathologies could lead to an amelioration of behavioral deficits. Hence, seemingly unrelated central and peripheral effects of prenatal infection could represent interrelated pathological entities that emerge in response to a common developmental stressor. Targeting peripheral abnormalities may thus represent a valuable strategy to improve the wide spectrum of behavioral abnormalities that can emerge in subjects with prenatal infection histories.

scholarly journals Developmental Exposure to DDT or DDE Alters Sympathetic Innervation of Brown Adipose in Adult Female Mice

2020 ◽  
Author(s):  
Annalise N vonderEmbse ◽  
Sarah E Elmore ◽  
Kyle B Jackson ◽  
Beth A Habecker ◽  
Katherine E Manz ◽  
...  
Keyword(s):  
Adult Female ◽  
Sympathetic Neurons ◽  
Sympathetic Innervation ◽  
Female Offspring ◽  
Developmental Exposure ◽  
Female Mice ◽  
Cl 316,243 ◽  
Brown Adipose ◽  
Increased Risk ◽  
Sympathetic Regulation

Abstract Background: Exposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated with increased risk of insulin resistance and obesity in humans and experimental animals. These effects appear to be mediated by reduced brown adipose tissue (BAT) thermogenesis, which is regulated by the sympathetic nervous system. Although the neurotoxicity of DDT is well-established, whether DDT alters sympathetic innervation of BAT is unknown. We hypothesized that perinatal exposure to DDT or DDE promotes thermogenic dysfunction by interfering with sympathetic regulation of BAT thermogenesis. Methods: Pregnant C57BL/6J mice were exposed by oral gavage to environmentally relevant concentrations of DDT (1.7 mg/kg) or DDE (1.31 mg/kg) from gestational day 11.5 to postnatal day 5, and longitudinal body temperature was recorded in male and female offspring. At 4 months of age, metabolic parameters were measured in female offspring via indirect calorimetry with or without the β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated.Results: We observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDT or DDE. Perinatal DDT exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDT nor DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDT-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDT, but not DDE, and 48% and 43% fewer synapses in stellate ganglia of mice exposed to either DDT or DDE, respectively, compared to control. Conclusions: These data demonstrate that perinatal DDT and DDE exposure impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT.

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