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Molecular Mechanisms of Endocrine-Disrupting Chemicals (EDC) Action in the Pathogenesis...
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Molecular Mechanisms of Endocrine-Disrupting Chemicals (EDC) Action in the Pathogenesis of Human Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 11147

Special Issue Editor

Prof. Dr. Dariusz Szukiewicz

E-Mail Website
Guest Editor
Department of Biophysics, Physiology and Pathophysiology, Faculty of Health Sciences, Medical University of Warsaw, Chalubinskiego 5 (4th Floor), 02-004 Warsaw, Poland
Interests: inflammation; cytokine network; human placenta; stem cells in reproductive tissues; pathophysiology of diabetes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Endocrine-disrupting chemicals are exogenous agents that interfere with the synthesis, secretion, transport, metabolism, binding action, or elimination of natural blood-borne hormones that are present in the body and are responsible for homeostasis, reproduction, and the developmental process. Many chemicals, both natural (e.g., phytoestrogens, some metals) and man-made (e.g., bisphenol A–BPA from plastics, dichlorodiphenyltrichloroethane–DDT from pesticides, and diethylstilbestrol–DES from pharmaceutical agents), may mimic or interfere with the body’s endocrine system. EDC-related adverse human health outcomes include abnormal function of the reproductive system, endometriosis, early puberty, certain cancers, altered nervous system function, immune disorders, growth disorders, respiratory and cardiovascular problems, and metabolic issues (e.g., diabetes, obesity). The broad spectrum of EDC activities includes, but is not limited to, estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ and retinoid signaling pathways. These are highly conserved in the evolution pathways and can be modeled in laboratory in vitro and in vivo models. The related research includes elaborating on better models and tools for understanding the mechanisms of EDC action, precise methods of EDC identification, understanding the relationship  between exposure to EDC and health efects, developing strategies to reduce or prevent exposures.

This Special Issue is dedicated to all aspects of EDC impact on human health and, in particular, EDC contribution to the pathogenesis of diseases in the context of new therapeutic strategies. When considering your submission, please keep in mind that IJMS is a journal of molecular science. However, submissions of clinical studies with biomolecular experiments or pathological research with case sample data are welcomed.

Prof. Dr. Dariusz Szukiewicz
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • endocrine-disrupting chemicals
  • environmental pollution
  • environmental health threats
  • endocrine disruption
  • abnormal estrogen signaling
  • metabolic imbalances
  • reproductive health
  • carcinogenesis

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Published Papers (3 papers)

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Research

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30 pages, 10172 KiB  
Article
Endocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer
by Diaaidden Alwadi, Quentin Felty, Changwon Yoo, Deodutta Roy and Alok Deoraj
Int. J. Mol. Sci. 2023, 24(4), 3191; https://doi.org/10.3390/ijms24043191 - 6 Feb 2023
Cited by 5 | Viewed by 3060
Abstract
Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men in the world. Its prevention has been limited because of an incomplete understanding of how environmental exposures to chemicals contribute to the molecular pathogenesis of aggressive PCa. Environmental exposures to [...] Read more.
Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men in the world. Its prevention has been limited because of an incomplete understanding of how environmental exposures to chemicals contribute to the molecular pathogenesis of aggressive PCa. Environmental exposures to endocrine-disrupting chemicals (EDCs) may mimic hormones involved in PCa development. This research aims to identify EDCs associated with PCa hub genes and/or transcription factors (TF) of these hub genes in addition to their protein–protein interaction (PPI) network. We are expanding upon the scope of our previous work, using six PCa microarray datasets, namely, GSE46602, GSE38241, GSE69223, GSE32571, GSE55945, and GSE26126, from the NCBI/GEO, to select differentially expressed genes based on |log2FC| (fold change) ≥ 1 and an adjusted p-value < 0.05. An integrated bioinformatics analysis was used for enrichment analysis (using DAVID.6.8, GO, KEGG, STRING, MCODE, CytoHubba, and GeneMANIA). Next, we validated the association of these PCa hub genes in RNA-seq PCa cases and controls from TCGA. The influence of environmental chemical exposures, including EDCs, was extrapolated using the chemical toxicogenomic database (CTD). A total of 369 overlapping DEGs were identified associated with biological processes, such as cancer pathways, cell division, response to estradiol, peptide hormone processing, and the p53 signaling pathway. Enrichment analysis revealed five up-regulated (NCAPG, MKI67, TPX2, CCNA2, CCNB1) and seven down-regulated (CDK1, CCNB2, AURKA, UBE2C, BUB1B, CENPF, RRM2) hub gene expressions. Expression levels of these hub genes were significant in PCa tissues with high Gleason scores ≥ 7. These identified hub genes influenced disease-free survival and overall survival of patients 60–80 years of age. The CTD studies showed 17 recognized EDCs that affect TFs (NFY, CETS1P54, OLF1, SRF, COMP1) that are known to bind to our PCa hub genes, namely, NCAPG, MKI67, CCNA2, CDK1, UBE2C, and CENPF. These validated differentially expressed hub genes can be potentially developed as molecular biomarkers with a systems perspective for risk assessment of a wide-ranging list of EDCs that may play overlapping and important role(s) in the prognosis of aggressive PCa. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Endocrine-Disrupting Chemicals (EDC) Action in the Pathogenesis of Human Diseases)
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Review

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53 pages, 10403 KiB  
Review
Insight into the Potential Mechanisms of Endocrine Disruption by Dietary Phytoestrogens in the Context of the Etiopathogenesis of Endometriosis
by Dariusz Szukiewicz
Int. J. Mol. Sci. 2023, 24(15), 12195; https://doi.org/10.3390/ijms241512195 - 30 Jul 2023
Cited by 5 | Viewed by 2961
Abstract
Phytoestrogens (PEs) are estrogen-like nonsteroidal compounds derived from plants (e.g., nuts, seeds, fruits, and vegetables) and fungi that are structurally similar to 17β-estradiol. PEs bind to all types of estrogen receptors, including ERα and ERβ receptors, nuclear receptors, and a membrane-bound estrogen receptor [...] Read more.
Phytoestrogens (PEs) are estrogen-like nonsteroidal compounds derived from plants (e.g., nuts, seeds, fruits, and vegetables) and fungi that are structurally similar to 17β-estradiol. PEs bind to all types of estrogen receptors, including ERα and ERβ receptors, nuclear receptors, and a membrane-bound estrogen receptor known as the G protein-coupled estrogen receptor (GPER). As endocrine-disrupting chemicals (EDCs) with pro- or antiestrogenic properties, PEs can potentially disrupt the hormonal regulation of homeostasis, resulting in developmental and reproductive abnormalities. However, a lack of PEs in the diet does not result in the development of deficiency symptoms. To properly assess the benefits and risks associated with the use of a PE-rich diet, it is necessary to distinguish between endocrine disruption (endocrine-mediated adverse effects) and nonspecific effects on the endocrine system. Endometriosis is an estrogen-dependent disease of unknown etiopathogenesis, in which tissue similar to the lining of the uterus (the endometrium) grows outside of the uterus with subsequent complications being manifested as a result of local inflammatory reactions. Endometriosis affects 10–15% of women of reproductive age and is associated with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. In this review, the endocrine-disruptive actions of PEs are reviewed in the context of endometriosis to determine whether a PE-rich diet has a positive or negative effect on the risk and course of endometriosis. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Endocrine-Disrupting Chemicals (EDC) Action in the Pathogenesis of Human Diseases)
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11 pages, 975 KiB  
Review
Endocrine Disruptors and Endometrial Cancer: Molecular Mechanisms of Action and Clinical Implications, a Systematic Review
by Donatella Caserta, Maria Paola De Marco, Aris Raad Besharat and Flavia Costanzi
Int. J. Mol. Sci. 2022, 23(6), 2956; https://doi.org/10.3390/ijms23062956 - 9 Mar 2022
Cited by 19 | Viewed by 4008
Abstract
It has been widely demonstrated that endocrine disruptors play a central role in various physiopathological processes of human health. In the literature, various carcinogenic processes have been associated with endocrine disruptors. A review of the molecular mechanisms underlying the interaction between endocrine disruptors [...] Read more.
It has been widely demonstrated that endocrine disruptors play a central role in various physiopathological processes of human health. In the literature, various carcinogenic processes have been associated with endocrine disruptors. A review of the molecular mechanisms underlying the interaction between endocrine disruptors and the endometrial cancer has been poorly developed. A systematic review was performed using PubMed®/MEDLINE. A total of 25 in vivo and in vitro works were selected. Numerous endocrine disruptors were analyzed. The most relevant results showed how Bisphenol A (BPA) interacts with the carcinogenesis process on several levels. It has been demonstrated how BPA can interact with hormonal receptors and with different transcription proliferative and antiproliferative factors. Furthermore, the effect of Polycyclic aromatic hydrocarbons on Aryl hydrocarbon receptors was investigated, and the role of flame retardants in promoting proliferation and metastasis was confirmed. The results obtained demonstrate how the mechanisms of action of endocrine disruptors are manifold in the pathophysiology of endometrial cancer, acting on different levels of the cancerogenesis process. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Endocrine-Disrupting Chemicals (EDC) Action in the Pathogenesis of Human Diseases)
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