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

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.

Download Full-text

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.

Download Full-text

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

Journal of Clinical Medicine ◽

10.3390/jcm9020405 ◽

2020 ◽

Vol 9 (2) ◽

pp. 405 ◽

Cited By ~ 2

Author(s):

Sophie-Christine de Aguiar Greca ◽

Ioannis Kyrou ◽

Ryan Pink ◽

Harpal Randeva ◽

Dimitris Grammatopoulos ◽

...

Keyword(s):

Bisphenol A ◽

Endocrine Disrupting Chemicals ◽

Cell Number ◽

Environmental Chemicals ◽

Related Factor ◽

Altered Expression ◽

Endocrine Disrupting Chemical ◽

Bewo Cells ◽

Endocrine Disrupting

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.

Download Full-text

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.

Download Full-text

Endocrine disrupting chemical, bisphenol-A, induces breast cancer associated gene HOXB9 expression in vitro and in vivo

Gene ◽

10.1016/j.gene.2016.05.009 ◽

2016 ◽

Vol 590 (2) ◽

pp. 234-243 ◽

Cited By ~ 35

Author(s):

Paromita Deb ◽

Arunoday Bhan ◽

Imran Hussain ◽

Khairul I. Ansari ◽

Samara A. Bobzean ◽

...

Keyword(s):

Breast Cancer ◽

Bisphenol A ◽

Endocrine Disrupting Chemical ◽

Endocrine Disrupting

Download Full-text

In vitro evidence for endocrine-disrupting chemical (EDC)’s inhibition of drug metabolism

African Health Sciences ◽

10.4314/ahs.v14i1.28 ◽

2014 ◽

Vol 14 (1) ◽

pp. 185 ◽

Cited By ~ 2

Author(s):

Wei-Ping Li ◽

Yu-Feng Wang ◽

Jian Gao ◽

Ming-Lian Yu ◽

Yan-Yang Tu ◽

...

Keyword(s):

Drug Metabolism ◽

Endocrine Disrupting Chemical ◽

Endocrine Disrupting

Download Full-text

Micropillar/Microwell Chip Assessment for Detoxification of Bisphenol A with Korean Pear (Pyrus pyrifolia)

Micromachines ◽

10.3390/mi11100922 ◽

2020 ◽

Vol 11 (10) ◽

pp. 922

Author(s):

Dong Lee ◽

Moo-Yeal Lee ◽

Sukkil Koh ◽

Mihi Yang

Keyword(s):

Bisphenol A ◽

Liver Cells ◽

Pyrus Pyrifolia ◽

Endocrine Disrupting Chemical ◽

Protein Levels ◽

Ic50 Value ◽

Endocrine Disrupting ◽

Cultured Liver Cells ◽

Ic50 Values ◽

Hep3b Cells

A micropillar/microwell chip platform with 3D cultured liver cells has been used for HTP screening of hepatotoxicity of bisphenol A (BPA), an endocrine-disrupting chemical. We previously found the hepatotoxicity of BPA is alleviated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase 2 (ALDH2). In this study, we have tested potential BPA detoxification with Korean pear (Pyrus pyrifolia) extract, stimulators of ADH and ALDH, as well as arbutin, a reference compound in the pears, on the micropillar/microwell chip platform with human liver cells. Surprisingly, the toxicity of BPA was reduced in the presence of Korean pear extract, indicated by significantly increased IC50 values. The IC50 value of BPA with Korean pear extract tested against HepG2 cells was shifted from 151 to 451 μM, whereas those tested against Hep3B cells was shifted from 110 to 204 μM. Among the tested various concentrations, 1.25, 2.5, and 5 mg/mL of the extract significantly reduced BPA toxicity (Ps < 0.05). However, there was no such detoxification effects with arbutin. This result was supported by changes in protein levels of ADH in the liver cells.

Download Full-text