Immune Cells in the Uterine Remodeling: Are They the Target of Endocrine Disrupting Chemicals?
Ontology highlight
ABSTRACT:
SUBMITTER: Meyer N
PROVIDER: S-EPMC7043066 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Immune Cells in the Uterine Remodeling: Are They the Target of Endocrine Disrupting Chemicals?
Meyer Nicole N Zenclussen Ana Claudia AC
Frontiers in immunology 20200219
Sufficient uterine remodeling is essential for fetal survival and development. Pathologies related to poor remodeling have a negative impact on maternal and fetal health even years after birth. Research of the last decades yielded excellent studies demonstrating the key role of immune cells in the remodeling processes. This review summarizes the current knowledge about the relevance of immune cells for uterine remodeling during pregnancy and further discusses immunomodulatory effects of man-made ...[more]
Similar Datasets
Project description:Purpose of reviewUterine leiomyoma (fibroids) is a gynecologic disorder impacting the majority of women in the United States. When symptomatic, these noncancerous tumors can cause severe morbidity including pelvic pain, menorrhagia, and infertility. Endocrine-disrupting chemicals (EDCs) may represent a modifiable risk factor. The aim of this review is to summarize recent human and experimental evidence on EDCs exposures and fibroids.Recent findingsMultiple EDCs are associated with fibroid outcomes and/or processes including phthalates, parabens, environmental phenols, alternate plasticizers, Diethylstilbestrol, organophosphate esters, and tributyltin. Epidemiologic studies suggest exposure to certain EDCs, such as di-(2-ethylhxyl)-phthalate (DEHP), are associated with increased fibroid risk and severity. Both human and experimental studies indicate that epigenetic processes may play an important role in linking EDCs to fibroid pathogenesis. In-vitro and in-vivo studies show that DEHP, bisphenol A, and diethylstilbestrol can impact biological pathways critical to fibroid pathogenesis.SummaryWhile research on EDCs and fibroids is still evolving, recent evidence suggests EDC exposures may contribute to fibroid risk and progression. Further research is needed to examine the impacts of EDC mixtures and to identify critical biological pathways and windows of exposure. These results could open the door to new prevention strategies for fibroids.
| S-EPMC8240765 | biostudies-literature
Project description:Since reports published in 2015 and 2016 identified 15 probable exposure-outcome associations, there has been an increase in studies in humans of exposure to endocrine-disrupting chemicals (EDCs) and a deepened understanding of their effects on human health. In this Series paper, we have reviewed subsequent additions to the literature and identified new exposure-outcome associations with substantial human evidence. Evidence is particularly strong for relations between perfluoroalkyl substances and child and adult obesity, impaired glucose tolerance, gestational diabetes, reduced birthweight, reduced semen quality, polycystic ovarian syndrome, endometriosis, and breast cancer. Evidence also exists for relations between bisphenols and adult diabetes, reduced semen quality, and polycystic ovarian syndrome; phthalates and prematurity, reduced anogenital distance in boys, childhood obesity, and impaired glucose tolerance; organophosphate pesticides and reduced semen quality; and occupational exposure to pesticides and prostate cancer. Greater evidence has accumulated than was previously identified for cognitive deficits and attention-deficit disorder in children following prenatal exposure to bisphenol A, organophosphate pesticides, and polybrominated flame retardants. Although systematic evaluation is needed of the probability and strength of these exposure-outcome relations, the growing evidence supports urgent action to reduce exposure to EDCs.
| S-EPMC7437820 | biostudies-literature
Project description:A growing epidemic of nonalcoholic fatty liver disease (NAFLD) is paralleling the increase in the incidence of obesity and diabetes mellitus in countries that consume a Western diet. As NAFLD can lead to life-threatening conditions such as cirrhosis and hepatocellular carcinoma, an understanding of the factors that trigger its development and pathological progression is needed. Although by definition this disease is not associated with alcohol consumption, exposure to environmental agents that have been linked to other diseases might have a role in the development of NAFLD. Here, we focus on one class of these agents, endocrine-disrupting chemicals (EDCs), and their potential to influence the initiation and progression of a cascade of pathological conditions associated with hepatic steatosis (fatty liver). Experimental studies have revealed several potential mechanisms by which EDC exposure might contribute to disease pathogenesis, including the modulation of nuclear hormone receptor function and the alteration of the epigenome. However, many questions remain to be addressed about the causal link between acute and chronic EDC exposure and the development of NAFLD in humans. Future studies that address these questions hold promise not only for understanding the linkage between EDC exposure and liver disease but also for elucidating the molecular mechanisms that underpin NAFLD, which in turn could facilitate the development of new prevention and treatment opportunities.
| S-EPMC5657429 | biostudies-literature
Project description:The emerging field of omics - large-scale data-rich biological measurements of the genome - provides new opportunities to advance and strengthen research into endocrine-disrupting chemicals (EDCs). Although some EDCs have been associated with adverse health effects in humans, our understanding of their impact remains incomplete. Progress in the field has been primarily limited by our inability to adequately estimate and characterize exposure and identify sensitive and measurable outcomes during windows of vulnerability. Evolving omics technologies in genomics, epigenomics and mitochondriomics have the potential to generate data that enhance exposure assessment to include the exposome - the totality of the lifetime exposure burden - and provide biology-based estimates of individual risks. Applying omics technologies to expand our knowledge of individual risk and susceptibility will augment biological data in the prediction of variability and response to disease, thereby further advancing EDC research. Together, refined exposure characterization and enhanced disease-risk prediction will help to bridge crucial gaps in EDC research and create opportunities to move the field towards a new vision - precision public health.
| S-EPMC7141602 | biostudies-literature
Project description:Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with endogenous hormonal systems at various levels, resulting in adverse health effects. EDCs belong to diverse chemical families and can accumulate in the environment, diet and body fluids, with different levels of persistence. Their action can be mediated by several receptors, including members of the nuclear receptor family, such as estrogen and androgen receptors. The G protein-coupled estrogen receptor (GPER), a seven-transmembrane domain receptor, has also attracted attention as a potential target of EDCs. This review summarizes our current knowledge concerning GPER as a mediator of EDCs' effects.
| S-EPMC7466721 | biostudies-literature
Project description:BackgroundGlobally, the burden of breast cancer has increased significantly in recent decades. Emerging evidence suggested that endocrine-disrupting chemicals (EDCs), which have the potential to interfere with the function of normal hormones, may play a crucial role in this trend. However, the potential relationships were inconsistent in various studies.Objective and search methodsIn our study, we sought to fully evaluate the currently available epidemiological evidence to ascertain whether certain EDC congeners and their metabolites are related to breast cancer risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search of original peer-reviewed publications in three electronic databases: PubMed, Web of Science, and Embase. Publications that covered xenobiotic EDC exposures and breast cancer-confirmed histological results or antecedent medical records or reporting to health registers were taken into consideration.OutcomesThe final result of the literature search was 6,498 references, out which we found 67 publications that matched the requirements for meta-analysis and eight publications for qualitative trend synthesis. In this meta-analysis, statistically significant associations revealed that (i) 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p'-DDT) and its major metabolite 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE) were somewhat related to a greater risk of breast cancer. However, this relationship only existed in blood serum but not in adipose tissue. (ii) Breast cancer risk was increased by exposure to chlordane and hexachlorocyclohexane. (iii) Five polychlorinated biphenyls (PCB 99, PCB 105, PCB 118, PCB 138, and PCB 183) can increase the risk of breast cancer. (iv) One phthalate congener (BBP) and one per- and polyfluoroalkyl substance congener (PFDoDA) were negatively associated with breast cancer risk. Unfortunately, heterogeneity was not well explained in our review, and a limited number of available prospective studies investigating the associations between EDC exposure and breast cancer were included in our meta-analysis. To elucidate the overall associations, future large, longitudinal epidemiological investigations are needed.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD 42023420927.
| S-EPMC10665889 | biostudies-literature
Project description:Synthetic endocrine disrupting chemicals (EDCs), omnipresent in food, household, and personal care products, have been implicated in adverse trends in human reproduction, including infertility and increasing demand for assisted reproduction. Here, we study the action of 96 ubiquitous EDCs on human sperm. We show that structurally diverse EDCs activate the sperm-specific CatSper channel and, thereby, evoke an intracellular Ca(2+) increase, a motility response, and acrosomal exocytosis. Moreover, EDCs desensitize sperm for physiological CatSper ligands and cooperate in low-dose mixtures to elevate Ca(2+) levels in sperm. We conclude that EDCs interfere with various sperm functions and, thereby, might impair human fertilization.
| S-EPMC4196979 | biostudies-literature
Project description:BackgroundEndocrine-disrupting chemicals (EDCs) influence the activity of estrogen receptors (ERs) and alter the function of the endocrine system. However, the diversity of EDC effects and mechanisms of action are poorly understood.ObjectivesWe examined the agonistic activity of EDCs through ERα and ERβ. We also investigated the effects of EDCs on ER-mediated target genes.MethodsHepG2 and HeLa cells were used to determine the agonistic activity of EDCs on ERα and ERβ via the luciferase reporter assay. Ishikawa cells stably expressing ERα were used to determine changes in endogenous ER target gene expression by EDCs.ResultsTwelve EDCs were categorized into three groups on the basis of product class and similarity of chemical structure. As shown by luciferase reporter analysis, the EDCs act as ER agonists in a cell type- and promoter-specific manner. Bisphenol A, bisphenol AF, and 2-2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (group 1) strongly activated ERα estrogen responsive element (ERE)-mediated responses. Daidzein, genistein, kaempferol, and coumestrol (group 2) activated both ERα and ERβ ERE-mediated activities. Endosulfan and kepone (group 3) weakly activated ERα. Only a few EDCs significantly activated the "tethered" mechanism via ERα or ERβ. Results of real-time polymerase chain reaction indicated that bisphenol A and bisphenol AF consistently activated endogenous ER target genes, but the activities of other EDCs on changes of ER target gene expression were compound specific.ConclusionAlthough EDCs with similar chemical structures (in the same group) tended to have comparable ERα and ERβ ERE-mediated activities, similar chemical structure did not correlate with previously reported ligand binding affinities of the EDCs. Using ERα-stable cells, we observed that EDCs differentially induced activity of endogenous ER target genes.
| S-EPMC3620735 | biostudies-literature
Project description:Equine Metabolic Syndrome (EMS) is characterized by abnormalities in insulin regulation, increased adiposity and laminitis, and has several similarities to human metabolic syndrome. A large amount of environmental variability in the EMS phenotype is not explained by commonly measured factors (diet, exercise, and season), suggesting that other environmental factors play a role in EMS development. Endocrine disrupting chemicals (EDCs) are associated with metabolic syndrome and other endocrine abnormalities in humans. This led us to hypothesize that EDCs are detectable in horse plasma and play a role in the pathophysiology of EMS. EDCs acting through the aryl hydrocarbon and estrogen receptors, were measured in plasma of 301 horses from 32 farms. The median (range) TEQ (2,3,7,8-TCDD equivalent) and EEQ (17?-estradiol equivalent) were 19.29?pg/g (0.59-536.36) and 10.50?pg/ml (4.35-15000.00), respectively. TEQ was negatively associated with plasma fat extracted and batch analyzed. EEQ was positively associated with pregnancy and batch analyzed, and negatively associated with being male and superfund score ?100 miles of the farm. Of particular interest, serum glucose and insulin, glucose and insulin post oral sugar challenge, and leptin concentrations were associated with EEQ, and serum triglyceride concentration was associated with TEQ. Overall, we demonstrated that EDCs are present in the plasma of horses and may explain some of the environmental variability in measured EMS phenotypes. This is the first example of EDCs being associated with clinical disease phenotype components in domestic animals.
| S-EPMC6347404 | biostudies-literature
Project description:Purpose of reviewEnvironmental toxicants are increasingly implicated in the global decline in metabolic health. Focusing on diabetes, herein, the molecular and cellular mechanisms by which metabolism disrupting chemicals (MDCs) impair energy homeostasis are discussed.Recent findingsEmerging data implicate MDC perturbations in a variety of pathways as contributors to metabolic disease pathogenesis, with effects in diverse tissues regulating fuel utilization. Potentiation of traditional metabolic risk factors, such as caloric excess, and emerging threats to metabolism, such as disruptions in circadian rhythms, are important areas of current and future MDC research. Increasing evidence also implicates deleterious effects of MDCs on metabolic programming that occur during vulnerable developmental windows, such as in utero and early post-natal life as well as pregnancy. Recent insights into the mechanisms by which MDCs alter energy homeostasis will advance the field's ability to predict interactions with classical metabolic disease risk factors and empower studies utilizing targeted therapeutics to treat MDC-mediated diabetes.
| S-EPMC5921937 | biostudies-literature