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The Role of Endocrine Disrupting Chemicals in the Feto-Placental Unit...
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The Role of Endocrine Disrupting Chemicals in the Feto-Placental Unit and Female Reproduction

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 17515

Special Issue Editors

Dr. Emmanouil Karteris

E-Mail Website
Guest Editor
Department of Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK
Interests: detection and characterisation of circulating tumour cells; use of liquid biopsies as cancer biomarkers of diagnostic and prognostic value; ovarian cancer; women's health; gynaecological cancers; role of endocrine-disrupting chemicals (EDCs) in pregnancy; 3D cultures/organ-on-a-chip
Special Issues, Collections and Topics in MDPI journals
Dr. Ioannis Kyrou

E-Mail Website
Guest Editor
1. Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
2. Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
3. Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry CV1 5FB, UK
4. Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK
5. Laboratory of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, 11855 Athens, Greece
Interests: metabolism and energy homeostasis; nutrition; cardiovascular endocrinology; cardiovascular disease and atherosclerosis; exercise and health; COVID 19; epidemiology of non-communicable diseases and public health; obesity and obesity-related complications; type 2 diabetes; non-alcoholic fatty liver disease (NAFLD); endocrinology; endocrine-disrupting chemicals; polycystic ovary syndrome (PCOS); mental-health stress and the HPA axis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Harpal S. Randeva

E-Mail Website
Guest Editor
1. Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
2. Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
Interests: women's health; endocrinology; gynaecological cancers; PCOS; metabolism; nutrition; diabetes; endocrine-disrupting chemicals (EDCs); links between obesity and cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Endocrine disrupting chemicals (EDCs) are environmental chemicals that interfere with physiological systems, adversely affecting the hormonal balance within various endocrine axes (particularly within the female reproductive system) or disrupting normal function in the target organs that these hormones regulate. EDCs include a variety of chemicals classes, such as industrial by-products, pesticides, and chemicals, used in manufacturing (particularly plastics). The US Centers for Disease Control and Prevention (CDC) have reported that more than 90% of 2000 individuals tested positive for chemicals in their blood. Moreover, in a report to the WHO (The State of the Science of Endocrine Disrupting Chemicals-2012), key concerns were raised regarding the “high incidence and the increasing trends of many endocrine-related disorders in humans”.

Emerging studies have linked EDCs with disorders at the placental level, -impact  later in adult life. Contributions to this Special Issue will advance our understanding of the role of EDCs in placentation, placental development and placental functions, which are key events for successful reproductive outcomes, as well as female reproduction as a whole. Moreover, we will be addressing how in utero exposures can adversely affect adult life.

Dr. Emmanouil Karteris
Dr. Ioannis Kyrou
Prof. Dr. Harpal S. Randeva
Guest Editors

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. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • EDCs
  • placenta
  • fetus
  • female reproduction
  • exposures
  • pregnancy
  • toxicity

Published Papers (4 papers)

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Research

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20 pages, 4097 KiB  
Article
Identification of Potential Bisphenol A (BPA) Exposure Biomarkers in Ovarian Cancer
by Aeman Zahra, Qiduo Dong, Marcia Hall, Jeyarooban Jeyaneethi, Elisabete Silva, Emmanouil Karteris and Cristina Sisu
J. Clin. Med. 2021, 10(9), 1979; https://doi.org/10.3390/jcm10091979 - 05 May 2021
Cited by 12 | Viewed by 3339
Abstract
Endocrine-disrupting chemicals (EDCs) can exert multiple deleterious effects and have been implicated in carcinogenesis. The xenoestrogen Bisphenol A (BPA) that is found in various consumer products has been involved in the dysregulation of numerous signalling pathways. In this paper, we present the analysis [...] Read more.
Endocrine-disrupting chemicals (EDCs) can exert multiple deleterious effects and have been implicated in carcinogenesis. The xenoestrogen Bisphenol A (BPA) that is found in various consumer products has been involved in the dysregulation of numerous signalling pathways. In this paper, we present the analysis of a set of 94 genes that have been shown to be dysregulated in presence of BPA in ovarian cancer cell lines since we hypothesised that these genes might be of biomarker potential. This study sought to identify biomarkers of disease and biomarkers of disease-associated exposure. In silico analyses took place using gene expression data extracted from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Differential expression was further validated at protein level using immunohistochemistry on an ovarian cancer tissue microarray. We found that 14 out of 94 genes are solely dysregulated in the presence of BPA, while the remaining 80 genes are already dysregulated (p-value < 0.05) in their expression pattern as a consequence of the disease. We also found that seven genes have prognostic power for the overall survival in OC in relation to their expression levels. Out of these seven genes, Keratin 4 (KRT4) appears to be a biomarker of exposure-associated ovarian cancer, whereas Guanylate Binding Protein 5 (GBP5), long intergenic non-protein coding RNA 707 (LINC00707) and Solute Carrier Family 4 Member 11 (SLC4A11) are biomarkers of disease. BPA can exert a plethora of effects that can be tissue- or cancer-specific. Our in silico findings generate a hypothesis around biomarkers of disease and exposure that could potentially inform regulation and policy making. Full article
(This article belongs to the Special Issue The Role of Endocrine Disrupting Chemicals in the Feto-Placental Unit and Female Reproduction)
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24 pages, 6868 KiB  
Article
Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation
by Sophie-Christine de Aguiar Greca, Ioannis Kyrou, Ryan Pink, Harpal Randeva, Dimitris Grammatopoulos, Elisabete Silva and Emmanouil Karteris
J. Clin. Med. 2020, 9(2), 405; https://doi.org/10.3390/jcm9020405 - 03 Feb 2020
Cited by 22 | Viewed by 5072
Abstract
Background: Endocrine-disrupting chemicals (EDCs) are environmental chemicals/toxicants that humans are exposed to, interfering with the action of multiple hormones. Bisphenol A (BPA) is classified as an EDC with xenoestrogenic activity with potentially adverse effects in reproduction. Currently, a significant knowledge gap remains regarding [...] Read more.
Background: Endocrine-disrupting chemicals (EDCs) are environmental chemicals/toxicants that humans are exposed to, interfering with the action of multiple hormones. Bisphenol A (BPA) is classified as an EDC with xenoestrogenic activity with potentially adverse effects in reproduction. Currently, a significant knowledge gap remains regarding the complete spectrum of BPA-induced effects on the human placenta. As such, the present study examined the effects of physiologically relevant doses of BPA in vitro. Methods: qRT-PCR, Western blotting, immunofluorescence, ELISA, microarray analyses, and bioinformatics have been employed to study the effects of BPA using nonsyncytialised (non-ST) and syncytialised (ST) BeWo cells. Results: Treatment with 3 nM BPA led to an increase in cell number and altered the phosphorylation status of p38, an effect mediated primarily via the membrane-bound estrogen receptor (GPR30). Nonbiased microarray analysis identified 1195 and 477 genes that were differentially regulated in non-ST BeWo cells, whereas in ST BeWo cells, 309 and 158 genes had altered expression when treated with 3 and 10 nM, respectively. Enriched pathway analyses in non-ST BeWo identified a leptin and insulin overlap (3 nM), methylation pathways (10 nM), and differentiation of white and brown adipocytes (common). In the ST model, most significantly enriched were the nuclear factor erythroid 2-related factor 2 (NRF2) pathway (3 nM) and mir-124 predicted interactions with cell cycle and differentiation (10 nM). Conclusion: Collectively, our data offer a new insight regarding BPA effects at the placental level, and provide a potential link with metabolic changes that can have an impact on the developing fetus. Full article
(This article belongs to the Special Issue The Role of Endocrine Disrupting Chemicals in the Feto-Placental Unit and Female Reproduction)
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Review

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16 pages, 1648 KiB  
Review
The Role of the 3Rs for Understanding and Modeling the Human Placenta
by Joana Costa, Ruth Mackay, Sophie-Christine de Aguiar Greca, Alessandro Corti, Elisabete Silva, Emmanouil Karteris and Arti Ahluwalia
J. Clin. Med. 2021, 10(15), 3444; https://doi.org/10.3390/jcm10153444 - 03 Aug 2021
Cited by 7 | Viewed by 3508
Abstract
Modeling the physiology of the human placenta is still a challenge, despite the great number of scientific advancements made in the field. Animal models cannot fully replicate the structure and function of the human placenta and pose ethical and financial hurdles. In addition, [...] Read more.
Modeling the physiology of the human placenta is still a challenge, despite the great number of scientific advancements made in the field. Animal models cannot fully replicate the structure and function of the human placenta and pose ethical and financial hurdles. In addition, increasingly stricter animal welfare legislation worldwide is incentivizing the use of 3R (reduction, refinement, replacement) practices. What efforts have been made to develop alternative models for the placenta so far? How effective are they? How can we improve them to make them more predictive of human pathophysiology? To address these questions, this review aims at presenting and discussing the current models used to study phenomena at the placenta level: in vivo, ex vivo, in vitro and in silico. We describe the main achievements and opportunities for improvement of each type of model and critically assess their individual and collective impact on the pursuit of predictive studies of the placenta in line with the 3Rs and European legislation. Full article
(This article belongs to the Special Issue The Role of Endocrine Disrupting Chemicals in the Feto-Placental Unit and Female Reproduction)
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15 pages, 1823 KiB  
Review
Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?
by Aeman Zahra, Cristina Sisu, Elisabete Silva, Sophie-Christine De Aguiar Greca, Harpal S. Randeva, Kamaljit Chatha, Ioannis Kyrou and Emmanouil Karteris
J. Clin. Med. 2020, 9(10), 3296; https://doi.org/10.3390/jcm9103296 - 14 Oct 2020
Cited by 17 | Viewed by 4450
Abstract
Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally [...] Read more.
Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation. Full article
(This article belongs to the Special Issue The Role of Endocrine Disrupting Chemicals in the Feto-Placental Unit and Female Reproduction)
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