scholarly journals Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences

2021 ◽  
Vol 12 ◽  
Author(s):  
Walter Lichtensteiger ◽  
Catherine Bassetti-Gaille ◽  
Hubert Rehrauer ◽  
Jelena Kühn Georgijevic ◽  
Jesus A.F. Tresguerres ◽  
...  

Endocrine disrupting chemicals (EDCs) can impair hippocampus-dependent behaviors in rat offspring and in children. In search for key processes underlying this effect, we compared the transcriptomes of rat hippocampus on postnatal day 6 after gestational and lactational exposure to three different EDCs at doses known to impair development of learning and memory. Aroclor 1254, a commercial PCB mixture (5 mg/kg or 0.5 mg/kg), or bisphenol A (5 mg/kg or 0.5 mg/kg) were administered in chow, chlorpyrifos (3 mg/kg or 1 mg/kg) was injected subcutaneously. Male hippocampus exhibited a common effect of all three chemicals on genes involved in cell-autonomous processes, Sox6, Sox11, Pou2f2/Oct2, and Pou3f2/Brn2, all upregulated at the high dose. Additional genes of the Sox and Pou families were affected by only one or two of the chemicals. Real time RT PCR showed a comparable expression change for bisphenol A also at the lower dose. Female hippocampus exhibited much fewer genes with expression changes (almost none with false discovery rate <0.05), and none of the genes of the Sox and Pou families was affected. Since gene network analyses in male hippocampus suggested a link between Sox6 and miR-24, known to be repressed by activation of ER-alpha and to repress Sox6 in other tissues, this microRNA was measured. miR-24 was downregulated by all chemicals at the high dose in males. Values of Sox6 mRNA and miR-24 were inversely correlated in individual male hippocampus samples, supporting the hypothesis that the change in Sox6 expression resulted from an action of miR-24. In contrast, miR-24 levels remained unchanged in hippocampus of females. A sexually dimorphic response of miR-24 may thus be at the basis of the sex difference in Sox6 expression changes following exposure to the three chemicals. ER-alpha expression was also sex-dependent, but the expression changes did not parallel those of potential downstream genes such as Sox6. Sox6 is known to suppress differentiation of Parvalbumin (Pvalb)-expressing interneurons. Individual Sox6 levels (FPKM) were inversely correlated with levels of Pvalb, but not with markers of Sox6-independent interneuron subpopulations, Nos1 and 5HT3aR. Effects on interneuron development are further suggested, in males, by expression changes of Nrg1 and its receptor Erbb4, controlling interneuron migration. Our study disclosed new types of EDC-responsive morphogenetic genes, and illustrated the potential relevance of microRNAs in sexually dimorphic EDC actions.

2005 ◽  
Vol 40 (4) ◽  
pp. 484-490 ◽  
Author(s):  
Keun J. Choi ◽  
Sang G. Kim ◽  
Chang W. Kim ◽  
Seung H. Kim

Abstract This study examined the effect of polyphosphate on removal of endocrine-disrupting chemicals (EDCs) such as nonylphenol and bisphenol-A by activated carbons. It was found that polyphosphate aided in the removal of nonylphenol and bisphenol- A. Polyphosphate reacted with nonylphenol, likely through dipole-dipole interaction, which then improved the nonylphenol removal. Calcium interfered with this reaction by causing competition. It was found that polyphosphate could accumulate on carbon while treating a river. The accumulated polyphosphate then aided nonylphenol removal. The extent of accumulation was dependent on the type of carbon. The accumulation occurred more extensively with the wood-based used carbon than with the coal-based used carbon due to the surface charge of the carbon. The negatively charged wood-based carbon attracted the positively charged calcium-polyphosphate complex more strongly than the uncharged coal-based carbon. The polyphosphate-coated activated carbon was also effective in nonylphenol removal. The effect was different depending on the type of carbon. Polyphosphate readily attached onto the wood-based carbon due to its high affinity for polyphosphate. The attached polyphosphate then improved the nonylphenol removal. However, the coating failed to attach polyphosphate onto the coal-based carbon. The nonylphenol removal performance of the coal-based carbon remained unchanged after the polyphosphate coating.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Diksha Sirohi ◽  
Ruqaiya Al Ramadhani ◽  
Luke D. Knibbs

AbstractPurposeEndocrine-related diseases and disorders are on the rise globally. Synthetically produced environmental chemicals (endocrine-disrupting chemicals (EDCs)) mimic hormones like oestrogen and alter signalling pathways. Endometriosis is an oestrogen-dependent condition, affecting 10–15% of women of the reproductive age, and has substantial impacts on the quality of life. The aetiology of endometriosis is believed to be multifactorial, ranging from genetic causes to immunologic dysfunction due to environmental exposure to EDCs. Hence, we undertook a systematic review and investigated the epidemiological evidence for an association between EDCs and the development of endometriosis. We also aimed to assess studies on the relationship between body concentration of EDCs and the severity of endometriosis.MethodFollowing PRISMA guidelines, a structured search of PubMed, Embase and Scopus was conducted (to July 2018). The included studies analysed the association between one or more EDCs and the prevalence of endometriosis. The types of EDCs, association and outcome, participant characteristics and confounding variables were extracted and analysed. Quality assessment was performed using standard criteria.ResultsIn total, 29 studies were included. Phthalate esters were positively associated with the prevalence of endometriosis. The majority (71%) of studies revealed a significant association between bisphenol A, organochlorinated environmental pollutants (dioxins, dioxin-like compounds, organochlorinated pesticides, polychlorinated biphenyls) and the prevalence of endometriosis. A positive association between copper, chromium and prevalence of endometriosis was demonstrated in one study only. Cadmium, lead and mercury were not associated with the prevalence of endometriosis. There were conflicting results for the association between nickel and endometriosis. The relationship of EDCs and severity of endometriosis was not established in the studies.ConclusionWe found some evidence to suggest an association between phthalate esters, bisphenol A, organochlorinated environmental pollutants and the prevalence of endometriosis. Disentangling these exposures from various other factors that affect endometriosis is complex, but an important topic for further research.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
E Haverinen ◽  
R Lange ◽  
H Tolonen

Abstract Increasing prevalence of metabolic syndrome (MetS) is causing significant health burden among the European population. Current knowledge supports the notion that endocrine disrupting chemicals (EDCs) interfere with human metabolism and hormonal balance, contributing to the conventionally recognized life-style related risk factors for MetS. In relation to the Human biomonitoring initiative (HBM4EU) five priority substances (Bisphenol A, Per- and polyfluoroalkyl substances (PFASs), Phthalates, Cadmium and Arsenic) and their association with adverse metabolic health effects were examined. A methodological framework for scoping reviews was followed to increase consistency and transparency throughout the process. A literature review was conducted to identify epidemiological studies focusing on the association between MetS or its individual components and the five HBM4EU priority substances. Human biomonitoring studies have been able to present evidence supporting EDC exposure and development of individual MetS components; however the strength of the association varies between the components and EDCs. Most of the identified literature examined Bisphenol A and Phthalate exposure, usually targeting obesity, anthropometrics or glucose metabolism. Evidence suggests a positive association between Bisphenol A and Phthalate exposure and obesity-related components. The substance group of PFASs indicated weakest association, as the results were inconsistent and were suggestive only for a positive association with development of dyslipidaemia. Current evidence on metabolic disturbances and EDCs are inconclusive and fragmented, hence establishing harmonized and standardized human biomonitoring procedures among the European population are needed. Rigorous and ongoing human biomonitoring in combination with health monitoring could provide comprehensive information on EDC exposure and association of metabolic disturbances. Key messages EDC exposure is ubiquitous within European population, hence more human biomonitoring in combination with health surveys is needed to strengthen knowledge on human’s metabolic health. MetS is an increasing global health concern, which requires novel approaches to tackle the challenge.


2002 ◽  
Vol 27 (5) ◽  
pp. 433-439 ◽  
Author(s):  
Hiroko YOSHINO ◽  
Toshio ICHIHARA ◽  
Mayumi KAWABE ◽  
Norio IMAI ◽  
Akihiro HAGIWARA ◽  
...  

2011 ◽  
Vol 23 (1) ◽  
pp. 20-30 ◽  
Author(s):  
Jing-Jing Li ◽  
Yong-Gui Yuan ◽  
Gang Hou ◽  
Xiang-Rong Zhang

Background: The molecular pathogenesis of depression and psychopharmacology of antidepressants remain elusive. Recent hypotheses suggest that changes in neurogenesis and plasticity may underlie the aetiology of depression. The hippocampus is affected by depression and shows neuronal remodelling during adulthood.Objective: The present study on the adult rat hippocampus, was to evaluate the dose-related effects of chronic venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic-AMP response element binding protein (pCREB).Methods: Sprague-Dawley rats were exposed to a variety of chronic unpredictable stressors (CUSs) to establish a depression model. Rats were treated for either 14 or 28 days with venlafaxine (5 and 10 mg/kg, respectively). The hippocampal expression of pCREB and BDNF mRNA and protein was assessed by using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction (RT-PCR).Results: Rats subjected to CUS procedure consumed less sucrose solution compared with non-stressed rats. The CUS influenced exploratory activity resulting in a reduction of the motility counts. Chronic low dose (5 mg/kg, 14 and 28 days), but not high dose (10 mg/kg, 14 and 28 days) of venlafaxine treatment increased the expression of pCREB and BDNF mRNA and protein in the CUS rat hippocampus.Conclusion: Neuronal plasticity-associated proteins such as pCREB and BDNF play an important role both in stress-related depression and in antidepressant effect.


2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Marita Chakhtoura ◽  
Uma Sriram ◽  
Michelle Heayn ◽  
Joshua Wonsidler ◽  
Christopher Doyle ◽  
...  

Sex hormones affect immune responses and might promote autoimmunity. Endocrine disrupting chemicals such as bisphenol A (BPA) may mimic their immune effects. Conventional dendritic cells (cDCs) are pivotal initiators of immune responses upon activation by danger signals coming from pathogens or distressed tissues through triggering of the Toll-like receptors (TLRs). We generated in vitro murine cDCs in the absence of estrogens and measured the effects of exogenously added estrogen or BPA on their differentiation and activation by the TLR ligands LPS and CpG. Estrogen enhanced the differentiation of GM-CSF-dependent cDCs from bone marrow precursors in vitro, and the selective estrogen receptor modulators (SERMs) tamoxifen and fulvestrant blocked these effects. Moreover, estrogen augmented the upregulation of costimulatory molecules and proinflammatory cytokines (IL-12p70 and TNFα) upon stimulation by TLR9 ligand CpG, while the response to LPS was less estrogen-dependent. These effects are partially explained by an estrogen-dependent regulation of TLR9 expression. BPA did not promote cDC differentiation nor activation upon TLR stimulation. Our results suggest that estrogen promotes immune responses by increasing DC activation, with a preferential effect on TLR9 over TLR4 stimulation, and highlight the influence of estrogens in DC cultures, while BPA does not mimic estrogen in the DC functions that we tested.


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