Nuclear receptors in transgenerational epigenetic inheritance

Ozgyin, Lilla; Erdős, Edina; Bojcsuk, Dóra; Bálint, Bálint László

doi:10.1016/j.pbiomolbio.2015.02.012

Cited by 31 publications

(20 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Exposure throughout gestation and perinatal development to BPA may further exacerbate the nonalcoholic steatohepatitis-like phenotype in male rats that were fed a high-fat diet post-weaning; in particular, BPA worsened the accumulation of lipids in hepatocytes as well as liver inflammation and oxidative stress fibrosis [600]. Liver function markers were unimpaired in BPA-exposed rats kept on a standard diet; however, these animals showed effects suggestive of subtle alterations of liver programming, such as moderately increased steatosis and altered expression of insulin signaling elements.…”

Section: Mdcs and Metabolism-relevant Diseasesmentioning

confidence: 99%

Metabolism disrupting chemicals and metabolic disorders

Heindel

Blumberg

Cave

et al. 2017

Reproductive Toxicology

815

651

View full text Add to dashboard Cite

The recent epidemics of metabolic diseases, obesity, type 2 diabetes(T2D), liver lipid disorders and metabolic syndrome have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence that other environmental factors may contribute to the rapid increase in the incidence of these metabolic diseases. This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders. It will then specifically focus on the role of endocrine disrupting chemicals (EDCs) in the etiology of obesity, T2D and NAFLD while finally integrating the information on EDCs on multiple metabolic disorders that could lead to metabolic syndrome. We will specifically examine evidence linking EDC exposures during critical periods of development with metabolic diseases that manifest later in life and across generations.

show abstract

Section: Mdcs and Metabolism-relevant Diseasesmentioning

confidence: 99%

Metabolism disrupting chemicals and metabolic disorders

Heindel

Blumberg

Cave

et al. 2017

Reproductive Toxicology

815

651

View full text Add to dashboard Cite

show abstract

“…Nuclear receptors, such as steroid receptors, are a family of transcription factors that, after activation by a ligand or multiple ligands, can bind directly to hormone-response elements in the DNA. These nuclear receptors can recruit chromatin-modifying complexes that include methyl-and acetyltransferases, directly altering epigenetic marks that regulate the expression of the target genes (21). By binding, activating or inhibiting nuclear receptors and other transcription factors, EDCs can modify local chromatin states as well as expression of histone and DNA modulators such as DNA or histone methyltransferases (22).…”

Section: Edc Mechanisms Of Action In Obesitymentioning

confidence: 99%

“…Several estrogenic EDCs, including genistein and bisphenol A (BPA), can activate ER␣ (21,25) and also induce transcription of ERs (26 -28). For BPA, it has been reported that activated ER␣ can associate to estrogen-responsive elements that are present in the promoter of the histone modifying methyltransferase EZH2.…”

Section: Edc Mechanisms Of Action In Obesitymentioning

confidence: 99%

The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals

Stel

Legler

2015

Endocrinology

View full text Add to dashboard Cite

Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.

show abstract

“…As for many other EDCs, interactions with nuclear sex hormone receptors and their ligand-dependent transcription factor activity (so-called genomic signaling mechanism) have been implicated as the principal molecular mechanism responsible for endocrine disrupting activity of MXC and VIN (Manikkam et al, 2014;Ozgyin et al, 2015;van Ravenzwaay et al, 2013). Although MXC is a weak estrogen receptor (ER) agonist, its hydroxylated metabolites, such as HPTE (2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane), are potent ERa agonists and weak antagonists to both ERß and androgen receptor (AR) (Gaido et al, 2000).…”

mentioning

confidence: 99%

“…Although MXC and VIN are being intensively investigated as prototypical EDCs in order to understand their mechanisms of endocrine disruption, epigenetic regulation and transgenerational inheritance (Manikkam et al, 2014;Ozgyin et al, 2015;Skinner, 2014), and even though rapid alterations of cellular signaling are being increasingly recognized as an important mechanism contributing to the adverse effects of EDCs (Trevino et al, 2015;Watson et al, 2014;Wong and Walker, 2013), there is only limited information about effects of MXC and VIN on rapid intercellular and intracellular signaling events, such as GJIC or mitogen-activated protein kinases (MAPKs).…”

mentioning

confidence: 99%

Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells

et al. 2016

View full text Add to dashboard Cite

Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC 50 values for GJIC inhibition being 10 mM for MXC and 126 mM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC via mechanisms involving rapid activation of PC-PLC occurring independently of ER-or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors.

show abstract

Nuclear receptors in transgenerational epigenetic inheritance

Cited by 31 publications

References 102 publications

Metabolism disrupting chemicals and metabolic disorders

Metabolism disrupting chemicals and metabolic disorders

The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals

Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells

Contact Info

Product

Resources

About