Editorial

4 pages, 177 KiB

Open AccessEditorial

A Silent Threat: Exploring the Impact of Endocrine Disruption on Human Health

by Yuet-Kin Leung

Int. J. Mol. Sci. 2023, 24(12), 9790; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24129790 - 06 Jun 2023

Cited by 2 | Viewed by 983

Endocrine-disrupting chemicals (EDCs) are chemicals, either natural or synthetic, that can interfere with the production, distribution, function, metabolism, or excretion of hormones in our body [...] Full article

(This article belongs to the Special Issue Endocrine Disruption and Human Diseases)

Research

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25 pages, 3835 KiB

Open AccessArticle

Low Dose of BPA Induces Liver Injury through Oxidative Stress, Inflammation and Apoptosis in Long–Evans Lactating Rats and Its Perinatal Effect on Female PND6 Offspring

by Beatriz Linillos-Pradillo, Lisa Rancan, Sergio D. Paredes, Margret Schlumpf, Walter Lichtensteiger, Elena Vara and Jesús Á. F. Tresguerres

Int. J. Mol. Sci. 2023, 24(5), 4585; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054585 - 26 Feb 2023

Cited by 7 | Viewed by 2037

Abstract

Bisphenol A (BPA) is a phenolic compound used in plastics elaboration for food protection or packaging. BPA-monomers can be released into the food chain, resulting in continuous and ubiquitous low-dose human exposure. This exposure during prenatal development is especially critical and could lead [...] Read more.

Bisphenol A (BPA) is a phenolic compound used in plastics elaboration for food protection or packaging. BPA-monomers can be released into the food chain, resulting in continuous and ubiquitous low-dose human exposure. This exposure during prenatal development is especially critical and could lead to alterations in ontogeny of tissues increasing the risk of developing diseases in adulthood. The aim was to evaluate whether BPA administration (0.036 mg/kg b.w./day and 3.42 mg/kg b.w./day) to pregnant rats could induce liver injury by generating oxidative stress, inflammation and apoptosis, and whether these effects may be observed in female postnatal day-6 (PND6) offspring. Antioxidant enzymes (CAT, SOD, GR, GPx and GST), glutathione system (GSH/GSSG) and lipid-DNA damage markers (MDA, LPO, NO, 8-OHdG) were measured using colorimetric methods. Inducers of oxidative stress (HO-1d, iNOS, eNOS), inflammation (IL-1β) and apoptosis (AIF, BAX, Bcl-2 and BCL-XL) were measured by qRT-PCR and Western blotting in liver of lactating dams and offspring. Hepatic serum markers and histology were performed. Low dose of BPA caused liver injury in lactating dams and had a perinatal effect in female PND6 offspring by increasing oxidative stress levels, triggering an inflammatory response and apoptosis pathways in the organ responsible for detoxification of this endocrine disruptor. Full article

(This article belongs to the Special Issue Endocrine Disruption and Human Diseases)

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18 pages, 3454 KiB

Open AccessArticle

Fetal Exposure to Endocrine Disrupting-Bisphenol A (BPA) Alters Testicular Fatty Acid Metabolism in the Adult Offspring: Relevance to Sperm Maturation and Quality

by Saikanth Varma, Archana Molangiri, Suryam Reddy Kona, Ahamed Ibrahim, Asim K. Duttaroy and Sanjay Basak

Int. J. Mol. Sci. 2023, 24(4), 3769; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043769 - 13 Feb 2023

Cited by 7 | Viewed by 1996

Abstract

Daily exposure to bisphenols can affect reproductive functions due to their pseudo-estrogenic and/or anti-androgenic effects. Testicular lipids contain high levels of polyunsaturated fatty acids necessary for sperm maturity, motility, and spermatogenesis. Whether prenatal exposure to bisphenols alters testicular fatty acid metabolism in adult [...] Read more.

Daily exposure to bisphenols can affect reproductive functions due to their pseudo-estrogenic and/or anti-androgenic effects. Testicular lipids contain high levels of polyunsaturated fatty acids necessary for sperm maturity, motility, and spermatogenesis. Whether prenatal exposure to bisphenols alters testicular fatty acid metabolism in adult offspring is unknown. Pregnant Wistar rats were gavaged from gestational day 4 to 21 with BPA and BPS (0.0, 0.4, 4.0, 40.0 μg/kg bw/day). Despite increased body and testis weight, the total testicular cholesterol, triglyceride, and plasma fatty acids were unaffected in the offspring. Lipogenesis was upregulated by increased SCD-1, SCD-2, and expression of lipid storage (ADRP) and trafficking protein (FABP4). The arachidonic acid, 20:4 n-6 (ARA) and docosapentaenoic acid, 22:5 n-6 (DPA) levels were decreased in the BPA-exposed testis, while BPS exposure had no effects. The expression of PPARα, PPARγ proteins, and CATSPER2 mRNA were decreased, which are important for energy dissipation and the motility of the sperm in the testis. The endogenous conversion of linoleic acid,18:2 n-6 (LA), to ARA was impaired by a reduced ARA/LA ratio and decreased FADS1 expression in BPA-exposed testis. Collectively, fetal BPA exposure affected endogenous long-chain fatty acid metabolism and steroidogenesis in the adult testis, which might dysregulate sperm maturation and quality. Full article

(This article belongs to the Special Issue Endocrine Disruption and Human Diseases)

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18 pages, 2204 KiB

Open AccessArticle

Effects of Subtoxic Concentrations of Atrazine, Cypermethrin, and Vinclozolin on microRNA-Mediated PI3K/Akt/mTOR Signaling in SH-SY5Y Cells

by Agnese Graziosi, Giulia Sita, Camilla Corrieri, Sabrina Angelini, Roberta d’Emmanuele di Villa Bianca, Emma Mitidieri, Raffaella Sorrentino, Patrizia Hrelia and Fabiana Morroni

Int. J. Mol. Sci. 2022, 23(23), 14538; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314538 - 22 Nov 2022

Cited by 2 | Viewed by 1320

Abstract

Endocrine-disrupting chemicals (EDCs) are different natural and synthetic chemicals that may interfere with several mechanisms of the endocrine system producing adverse developmental, metabolic, reproductive, and neurological effects in both human beings and wildlife. Among pesticides, numerous chemicals have been identified as EDCs. MicroRNAs [...] Read more.

Endocrine-disrupting chemicals (EDCs) are different natural and synthetic chemicals that may interfere with several mechanisms of the endocrine system producing adverse developmental, metabolic, reproductive, and neurological effects in both human beings and wildlife. Among pesticides, numerous chemicals have been identified as EDCs. MicroRNAs (miRNAs) can regulate gene expression, making fine adjustments in mRNA abundance and regulating proteostasis. We hypothesized that exposure to low doses of atrazine, cypermethrin, and vinclozolin may lead to effects on miRNA expression in SH-SY5Y cells. In particular, the exposure of SH-SY5Y cells to subtoxic concentrations of vinclozolin is able to downregulate miR-29b-3p expression leading to the increase in the related gene expression of ADAM12 and CDK6, which may promote a pro-oncogenic response through the activation of the PI3K/Akt/mTOR pathway and counteracting p53 activity. A better understanding of the molecular mechanisms of EDCs could provide important insight into their role in human disease. Full article

(This article belongs to the Special Issue Endocrine Disruption and Human Diseases)

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22 pages, 2491 KiB

Open AccessArticle

Select Per- and Polyfluoroalkyl Substances (PFAS) Induce Resistance to Carboplatin in Ovarian Cancer Cell Lines

by Brittany P. Rickard, Xianming Tan, Suzanne E. Fenton and Imran Rizvi

Int. J. Mol. Sci. 2022, 23(9), 5176; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23095176 - 05 May 2022

Cited by 8 | Viewed by 3240

Abstract

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants associated with adverse reproductive outcomes including reproductive cancers in women. PFAS can alter normal ovarian function, but the effects of PFAS on ovarian cancer progression and therapy response remain understudied. Ovarian cancer is the [...] Read more.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants associated with adverse reproductive outcomes including reproductive cancers in women. PFAS can alter normal ovarian function, but the effects of PFAS on ovarian cancer progression and therapy response remain understudied. Ovarian cancer is the most lethal gynecologic malignancy, and a major barrier to effective treatment is resistance to platinum-based chemotherapy. Platinum resistance may arise from exposure to external stimuli such as environmental contaminants. This study evaluated PFAS and PFAS mixture exposures to two human ovarian cancer cell lines to evaluate the ability of PFAS exposure to affect survival fraction following treatment with carboplatin. This is the first study to demonstrate that, at sub-cytotoxic concentrations, select PFAS and PFAS mixtures increased survival fraction in ovarian cancer cells following carboplatin treatment, indicative of platinum resistance. A concomitant increase in mitochondrial membrane potential, measured by the JC-1 fluorescent probe, was observed in PFAS-exposed and PFAS + carboplatin-treated cells, suggesting a potential role for altered mitochondrial function that requires further investigation. Full article

(This article belongs to the Special Issue Endocrine Disruption and Human Diseases)

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31 pages, 4322 KiB

Open AccessArticle

Environmental Phenol and Paraben Exposure Risks and Their Potential Influence on the Gene Expression Involved in the Prognosis of Prostate Cancer

by Diaaidden Alwadi, Quentin Felty, Deodutta Roy, Changwon Yoo and Alok Deoraj

Int. J. Mol. Sci. 2022, 23(7), 3679; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073679 - 27 Mar 2022

Cited by 8 | Viewed by 3775

Abstract

Prostate cancer (PCa) is one of the leading malignant tumors in US men. The lack of understanding of the molecular pathology on the risk of food supply chain exposures of environmental phenol (EP) and paraben (PB) chemicals limits the prevention, diagnosis, and treatment [...] Read more.

Prostate cancer (PCa) is one of the leading malignant tumors in US men. The lack of understanding of the molecular pathology on the risk of food supply chain exposures of environmental phenol (EP) and paraben (PB) chemicals limits the prevention, diagnosis, and treatment options. This research aims to utilize a risk assessment approach to demonstrate the association of EP and PB exposures detected in the urine samples along with PCa in US men (NHANES data 2005–2015). Further, we employ integrated bioinformatics to examine how EP and PB exposure influences the molecular pathways associated with the progression of PCa. The odds ratio, multiple regression model, and Pearson coefficients were used to evaluate goodness-of-fit analyses. The results demonstrated associations of EPs, PBs, and their metabolites, qualitative and quantitative variables, with PCa. The genes responsive to EP and PB exposures were identified using the Comparative Toxicogenomic Database (CTD). DAVID.6.8, GO, and KEGG enrichment analyses were used to delineate their roles in prostate carcinogenesis. The plug-in CytoHubba and MCODE completed identification of the hub genes in Cytoscape software for their roles in the PCa prognosis. It was then validated by using the UALCAN database by evaluating the expression levels and predictive values of the identified hub genes in prostate cancer prognosis using TCGA data. We demonstrate a significant association of higher levels of EPs and PBs in the urine samples, categorical and numerical confounders, with self-reported PCa cases. The higher expression levels of the hub genes (BUB1B, TOP2A, UBE2C, RRM2, and CENPF) in the aggressive stages (Gleason score > 8) of PCa tissues indicate their potential role(s) in the carcinogenic pathways. Our results present an innovative approach to extrapolate and validate hub genes responsive to the EPs and PBs, which may contribute to the severity of the disease prognosis, especially in the older population of US men. Full article

(This article belongs to the Special Issue Endocrine Disruption and Human Diseases)

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Review

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12 pages, 283 KiB

Open AccessReview

Association of Preterm Birth and Exposure to Endocrine Disrupting Chemicals

by Anish S. Kolan and Julianne M. Hall

Int. J. Mol. Sci. 2023, 24(3), 1952; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24031952 - 19 Jan 2023

Cited by 11 | Viewed by 2153

Abstract

Several studies in recent years have shown that endocrine disrupting chemicals (EDCs) can exert deleterious effects within several systems of the human body, such as the immune, neurological, and reproductive systems, among others. This review aims to summarize the investigations into the effect [...] Read more.

Several studies in recent years have shown that endocrine disrupting chemicals (EDCs) can exert deleterious effects within several systems of the human body, such as the immune, neurological, and reproductive systems, among others. This review aims to summarize the investigations into the effect of EDC exposure on reproductive systems, namely preterm birth (PTB), and the efforts that international organizations have made to curb the harmful results of EDC exposure. To gather information, PubMed was initially searched for relevant articles containing the following terms: endocrine disrupting chemicals; preterm birth. PubMed was subsequently used to identify articles discussing the association between preterm birth and specific EDC exposures (BPA; phthalates; organochlorine pesticides; organophosphate pesticides; lead; PBDE; preterm birth). Both searches, limited to articles published within the past 20 years, identified several publications that have examined the association between various EDCs and PTB. While the findings of the studies differed, collectively they revealed sufficient evidence of a potential association between EDC exposure and risk of PTB. Thus, international organizations such as the United Nations Environmental Programme (UNEP) and World Health Organization (WHO) should continue to limit EDC exposure across the globe and monitor levels among individuals of reproductive age. Full article

(This article belongs to the Special Issue Endocrine Disruption and Human Diseases)

15 pages, 674 KiB

Open AccessReview

Epigenetic Inheritance: Intergenerational Effects of Pesticides and Other Endocrine Disruptors on Cancer Development

by Heloiza Diniz Nicolella and Sonia de Assis

Int. J. Mol. Sci. 2022, 23(9), 4671; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094671 - 23 Apr 2022

Cited by 16 | Viewed by 3272

Abstract

Parental environmental experiences affect disease susceptibility in the progeny through epigenetic inheritance. Pesticides are substances or mixtures of chemicals—some of which are persistent environmental pollutants—that are used to control pests. This review explores the evidence linking parental exposure to pesticides and endocrine disruptors [...] Read more.

Parental environmental experiences affect disease susceptibility in the progeny through epigenetic inheritance. Pesticides are substances or mixtures of chemicals—some of which are persistent environmental pollutants—that are used to control pests. This review explores the evidence linking parental exposure to pesticides and endocrine disruptors to intergenerational and transgenerational susceptibility of cancer in population studies and animal models. We also discuss the impact of pesticides and other endocrine disruptors on the germline epigenome as well as the emerging evidence for how epigenetic information is transmitted between generations. Finally, we discuss the importance of this mode of inheritance in the context of cancer prevention and the challenges ahead. Full article

(This article belongs to the Special Issue Endocrine Disruption and Human Diseases)

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12 pages, 2203 KiB

Open AccessReview

Male Infertility in the XXI Century: Are Obesogens to Blame?

by Ana C. A. Sousa, Marco G. Alves, Pedro F. Oliveira, Branca M. Silva and Luís Rato

Int. J. Mol. Sci. 2022, 23(6), 3046; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063046 - 11 Mar 2022

Cited by 7 | Viewed by 2578

Abstract

The permanent exposure to environmental contaminants promoting weight gain (i.e., obesogens) has raised serious health concerns. Evidence suggests that obesogens are one of the leading causes of the marked decline in male fertility and are key players in shaping future health outcomes, not [...] Read more.

The permanent exposure to environmental contaminants promoting weight gain (i.e., obesogens) has raised serious health concerns. Evidence suggests that obesogens are one of the leading causes of the marked decline in male fertility and are key players in shaping future health outcomes, not only for those who are directly exposed to them, but also for upcoming generations. It has been hypothesized that obesogens affect male fertility. By using an interdisciplinary strategy, combining in silico, in vitro, in vivo and epidemiological findings, this review aims to contribute to the biological understanding of the molecular transformations induced by obesogens that are the basis of male infertility. Such understanding is shaped by the use of Adverse Outcomes Pathways, a new approach that may shift the paradigm of reproductive toxicology, contributing to the improvement of the diagnosis and management of the adverse effects of obesogens in male fertility. Full article

(This article belongs to the Special Issue Endocrine Disruption and Human Diseases)

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