Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation

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.

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Environmental exposures to endocrine disrupting chemicals (EDCs) and their role in endometriosis: a systematic literature review

Reviews on Environmental Health ◽

10.1515/reveh-2020-0046 ◽

2020 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Diksha Sirohi ◽

Ruqaiya Al Ramadhani ◽

Luke D. Knibbs

Keyword(s):

Bisphenol A ◽

Phthalate Esters ◽

Endocrine Disrupting Chemicals ◽

Environmental Pollutants ◽

Positive Association ◽

Environmental Chemicals ◽

Reproductive Age ◽

Organochlorinated Pesticides ◽

Endocrine Disrupting ◽

The Relationship

AbstractPurposeEndocrine-related diseases and disorders are on the rise globally. Synthetically produced environmental chemicals (endocrine-disrupting chemicals (EDCs)) mimic hormones like oestrogen and alter signalling pathways. Endometriosis is an oestrogen-dependent condition, affecting 10–15% of women of the reproductive age, and has substantial impacts on the quality of life. The aetiology of endometriosis is believed to be multifactorial, ranging from genetic causes to immunologic dysfunction due to environmental exposure to EDCs. Hence, we undertook a systematic review and investigated the epidemiological evidence for an association between EDCs and the development of endometriosis. We also aimed to assess studies on the relationship between body concentration of EDCs and the severity of endometriosis.MethodFollowing PRISMA guidelines, a structured search of PubMed, Embase and Scopus was conducted (to July 2018). The included studies analysed the association between one or more EDCs and the prevalence of endometriosis. The types of EDCs, association and outcome, participant characteristics and confounding variables were extracted and analysed. Quality assessment was performed using standard criteria.ResultsIn total, 29 studies were included. Phthalate esters were positively associated with the prevalence of endometriosis. The majority (71%) of studies revealed a significant association between bisphenol A, organochlorinated environmental pollutants (dioxins, dioxin-like compounds, organochlorinated pesticides, polychlorinated biphenyls) and the prevalence of endometriosis. A positive association between copper, chromium and prevalence of endometriosis was demonstrated in one study only. Cadmium, lead and mercury were not associated with the prevalence of endometriosis. There were conflicting results for the association between nickel and endometriosis. The relationship of EDCs and severity of endometriosis was not established in the studies.ConclusionWe found some evidence to suggest an association between phthalate esters, bisphenol A, organochlorinated environmental pollutants and the prevalence of endometriosis. Disentangling these exposures from various other factors that affect endometriosis is complex, but an important topic for further research.

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Epigenetic effects of Bisphenol A on granulosa cells of mouse follicles during in vitro culture: An experimental study

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v19i2.8471 ◽

2021 ◽

Author(s):

Aylin Jamali Khaghani ◽

Parisa Farrokh ◽

Saeed Zavareh

Keyword(s):

Bisphenol A ◽

Granulosa Cells ◽

Promoter Methylation ◽

Inhibitory Effect ◽

Promoter Regions ◽

Endocrine Disrupting Chemical ◽

Epigenetic Effects ◽

Endocrine Disrupting ◽

The Impact

Background: Bisphenol A (BPA), a synthetic endocrine-disrupting chemical, is a reproductive toxicant. Granulosa cells have significant roles in follicle development, and KIT ligand (KITL) and Anti-Müllerian hormone (AMH) are essential biomolecules produced by them during folliculogenesis. Objective: Due to the widespread use of BPA and its potential epigenetic effects, this study examined the impact of BPA on promoter methylation of amh and kitl genes in mouse granulosa cells. Materials and Methods: Preantral follicles were isolated from ovaries of immature mice and cultured for eight days. Then, follicles were treated with 50 and 100 μM of BPA, and 0.01% (v/v) ethanol for 24 and 72 hr. Growth and degeneration of follicles and antrum formation were analyzed. The granulosa cells were isolated mechanically, and their extracted DNA was treated with sodium bisulfite. The promoter regions of the amh and kitl were analyzed with PCR and sequencing. Results: BPA did not change follicle survival and antrum formation significantly (p = 0.41). However, the culture in the presence of 100 μM BPA had an inhibitory effect on growth. Before BPA treatment, the CpG of the kitl and amh promoters were unmethylated and partially methylated, respectively. While the percent of 5mC in the amh promoter reduced at 100 μM of BPA, it did not alter the kitl promoter methylation. Conclusion: BPA at higher concentrations has an inhibitory effect on follicle growth. Moreover, it seems that the epigenetic impact of BPA restricts to the demethylation of CpG sites. Key words: Bisphenol A, DNA methylation, Granulosa cells.

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Exposure to Endocrine Disrupting Chemicals and Risk of Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21239139 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9139

Author(s):

Louisane Eve ◽

Béatrice Fervers ◽

Muriel Le Romancer ◽

Nelly Etienne-Selloum

Keyword(s):

Breast Cancer ◽

Mammary Gland ◽

Disease Incidence ◽

Endocrine Disrupting Chemicals ◽

Epidemiological Studies ◽

Environmental Chemicals ◽

Endocrine Disrupting ◽

Carcinogenic Effects ◽

The Many

Breast cancer (BC) is the second most common cancer and the fifth deadliest in the world. Exposure to endocrine disrupting pollutants has been suggested to contribute to the increase in disease incidence. Indeed, a growing number of researchershave investigated the effects of widely used environmental chemicals with endocrine disrupting properties on BC development in experimental (in vitro and animal models) and epidemiological studies. The complex effects of endocrine disrupting chemicals (EDCs) on hormonal pathways, involving carcinogenic effects and an increase in mammary gland susceptibility to carcinogenesis—together with the specific characteristics of the mammary gland evolving over the course of life and the multifactorial etiology of BC—make the evaluation of these compounds a complex issue. Among the many EDCs suspected of increasing the risk of BC, strong evidence has only been provided for few EDCs including diethylstilbestrol, dichlorodiphenyltrichloroethane, dioxins and bisphenol A. However, given the ubiquitous nature and massive use of EDCs, it is essential to continue to assess their long-term health effects, particularly on carcinogenesis, to eradicate the worst of them and to sensitize the population to minimize their use.

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Bisphenol A Analogues: A Brief Review of their Occurrence in Food, Biological Samples and Endocrine Effects

Archives of Ecotoxicology ◽

10.36547/ae.2020.2.4.89-94 ◽

2020 ◽

Vol 2 (4) ◽

pp. 89-94

Author(s):

Nikola Knizatova ◽

Katarína Tokárová ◽

Hana Greifová ◽

Tomáš Jambor ◽

Peter Massányi ◽

...

Keyword(s):

Bisphenol A ◽

Human Health ◽

Human Exposure ◽

Food Packaging ◽

In Vitro Tests ◽

Endocrine Disrupting Chemical ◽

Endocrine Disrupting ◽

Made In

Bisphenol A (BPA) is the most well-known compound from the bisphenol family. There is increasing evidence that bisphenol BPA used in plastics, receipts, food packaging, and other products might be harmful to human health due to its actions as an endocrine-disrupting chemical, therefore BPA is being replaced by compounds very similar in structure, but data on the occurrence and effects of these BPA analogs are limited. Therefore, there is increasing concern regarding human exposure to bisphenol analogs (BPs) due to their widespread use and potential adverse effects. The main objective of this work was to investigate human exposure to BPs and the associated endocrine activities. We performed a literature review of the available research made in humans, in in vivo and in vitro tests. The findings support the idea that exposure to BPs may have an impact on human health, especially in terms of endocrine disruption.

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Effects of the endocrine disrupting chemical bisphenol A (BPA) in human placentation in vitro

Endocrine Abstracts ◽

10.1530/endoabs.65.p358 ◽

2019 ◽

Author(s):

Sophie-Christine de Aguiar Greca ◽

Ioannis Kyrou ◽

Ryan Pink ◽

Harpal Randeva ◽

Dimitris Grammatopoulos ◽

...

Keyword(s):

Bisphenol A ◽

Endocrine Disrupting Chemical ◽

Endocrine Disrupting

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The different effects of endocrine-disrupting chemicals on estrogen receptor-mediated transcription through interaction with coactivator TRAP220 in uterine tissue

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0310551 ◽

2003 ◽

Vol 31 (3) ◽

pp. 551-561 ◽

Cited By ~ 21

Author(s):

H Inoshita ◽

H Masuyama ◽

Y Hiramatsu

Keyword(s):

Estrogen Receptor ◽

Bisphenol A ◽

Endocrine Disrupting Chemicals ◽

Endocrine Function ◽

Uterine Tissue ◽

Present Evidence ◽

Endocrine Disrupting Chemical ◽

Positive Effects ◽

Endocrine Disrupting

An endocrine-disrupting chemical (EDC) can alter endocrine functions through a variety of mechanisms, including nuclear receptor-mediated changes in protein synthesis, interference with membrane receptor binding, steroidogenesis or synthesis of other hormones. Although major chemicals have been shown to disrupt estrogenic actions mainly through their binding to estrogen receptor (ER) or androgen receptor, it is not clear how EDCs affect endocrine functions in vivo. We present evidence that the EDCs bisphenol A and phthalate activate ER-mediated transcription through interaction with TRAP220. Moreover, bisphenol A had positive effects on the interaction between ER-beta and TRAP220 and on the expression of ER-beta and TRAP220 compared with phthalate and estradiol in uterine tIssue. These data suggested that some EDCs might alter endocrine function through the change of the receptor and coactivator levels in uterine tIssue and through the different effect on the interaction between ERs and coactivator TRAP220.

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Differential Estrogenic Actions of Endocrine-Disrupting Chemicals Bisphenol A, Bisphenol AF, and Zearalenone through Estrogen Receptor α and β in Vitro

Environmental Health Perspectives ◽

10.1289/ehp.1104689 ◽

2012 ◽

Vol 120 (7) ◽

pp. 1029-1035 ◽

Cited By ~ 136

Author(s):

Yin Li ◽

Katherine A. Burns ◽

Yukitomo Arao ◽

Colin J. Luh ◽

Kenneth S. Korach

Keyword(s):

Estrogen Receptor ◽

Bisphenol A ◽

Endocrine Disrupting Chemicals ◽

Estrogen Receptor Α ◽

Endocrine Disrupting ◽

Bisphenol Af

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The role of bisphenol A and its analogues as endocrine disruptors influencing the thyroid gland: a short review

Journal of Medical Science ◽

10.20883/medical.e441 ◽

2020 ◽

Vol 89 (3) ◽

pp. e441

Author(s):

Justyna Milczarek-Banach ◽

Piotr Miśkiewicz

Keyword(s):

Thyroid Gland ◽

Bisphenol A ◽

Metabolic Disorders ◽

Short Review ◽

Endocrine Disrupting Chemical ◽

Endocrine Disrupting ◽

The Impact ◽

The Relationship

Bisphenols (BPs) are common plastic additives widely used in industry, hence, human exposure to BPs is inevitable. The best known BP is bisphenol A (BPA), the production of which and its analogues has been increasing worldwide. This chemical is classified as an endocrine-disrupting chemical, inferring with hormonal homeostasis. Indeed, BPA is associated with the development of oestrogen-dependent neoplasms, infertility, metabolic disorders and neurobehavioral disturbances. However, there is a lack of evidence regarding the impact of BPA and its analogues on the thyroid, with most studies mainly performed on animals or in vitro. This review aims to summarise the knowledge regarding the relationship between BPA and its analogues on the thyroid gland.

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Experimental Approaches for Characterizing the Endocrine-Disrupting Effects of Environmental Chemicals in Fish

Frontiers in Endocrinology ◽

10.3389/fendo.2020.619361 ◽

2021 ◽

Vol 11 ◽

Author(s):

Fritzie T. Celino-Brady ◽

Darren T. Lerner ◽

Andre P. Seale

Keyword(s):

Developmental Stages ◽

Endocrine Disrupting Chemicals ◽

Endocrine System ◽

Environmental Chemicals ◽

Endocrine Disrupting ◽

Aquatic Vertebrates ◽

In The Wild ◽

Experimental Approaches

Increasing industrial and agricultural activities have led to a disturbing increase of pollutant discharges into the environment. Most of these pollutants can induce short-term, sustained or delayed impacts on developmental, physiological, and behavioral processes that are often regulated by the endocrine system in vertebrates, including fish, thus they are termed endocrine-disrupting chemicals (EDCs). Physiological impacts resulting from the exposure of these vertebrates to EDCs include abnormalities in growth and reproductive development, as many of the prevalent chemicals are capable of binding the receptors to sex steroid hormones. The approaches employed to investigate the action and impact of EDCs is largely dependent on the specific life history and habitat of each species, and the type of chemical that organisms are exposed to. Aquatic vertebrates, such as fish, are among the first organisms to be affected by waterborne EDCs, an attribute that has justified their wide-spread use as sentinel species. Many fish species are exposed to these chemicals in the wild, for either short or prolonged periods as larvae, adults, or both, thus, studies are typically designed to focus on either acute or chronic exposure at distinct developmental stages. The aim of this review is to provide an overview of the approaches and experimental methods commonly used to characterize the effects of some of the environmentally prevalent and emerging EDCs, including 17 α-ethinylestradiol, nonylphenol, BPA, phthalates, and arsenic; and the pervasive and potential carriers of EDCs, microplastics, on reproduction and growth. In vivo and in vitro studies are designed and employed to elucidate the direct effects of EDCs at the organismal and cellular levels, respectively. In silico approaches, on the other hand, comprise computational methods that have been more recently applied with the potential to replace extensive in vitro screening of EDCs. These approaches are discussed in light of model species, age and duration of EDC exposure.

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