Bisphenol A, Bisphenol F, and Bisphenol S: The Bad and the Ugly. Where Is the Good?

Abstract

Background: Bisphenol A (BPA), a reprotoxic and endocrine-disrupting chemical, has been substituted by alternative bisphenols such as bisphenol F (BPF) and bisphenol S (BPS) in the plastic industry. Despite their detection in placenta and amniotic fluids, the effects of bisphenols on human placental cells have not been characterized. Our objective was to explore in vitro and to compare the toxicity of BPA to its substitutes BPF and BPS to highlight their potential risks for placenta and then pregnancy. Methods: Human placenta cells (JEG-Tox cells) were incubated with BPA, BPF, and BPS for 72 h. Cell viability, cell death, and degenerative P2X7 receptor and caspases activation, and chromatin condensation were assessed using microplate cytometry and fluorescence microscopy. Results: Incubation with BPA, BPF, or BPS was associated with P2X7 receptor activation and chromatin condensation. BPA and BPF induced more caspase-1, caspase-9, and caspase-3 activation than BPS. Only BPF enhanced caspase-8 activity. Conclusions: BPA, BPF, and BPS are all toxic to human placental cells, with the P2X7 receptor being a common key element. BPA substitution by BPF and BPS does not appear to be a safe alternative for human health, particularly for pregnant women and their fetuses.

Forskolin Induces Endocrine Disturbance in Human JEG-3 Placental Cells

“…To perform our study, we selected a human placental model, the JEG-3 cells, as we previously demonstrated that JEG-Tox cells can be of great value in placental toxicology studies [ 28 ]. We demonstrated in our previous work in these cells that the activation of the P2X7 receptor is a marker of placental toxicity including endocrine-disrupting chemical-induced toxicity, as we highlighted that the well-known endocrine-disrupting chemicals known as bisphenol A or diethylstilbestrol, despite their chemical differences, shared a common mechanism: the activation of the P2X7 degenerative receptor in human placental cells [ 25 , 26 , 27 ]. Our results showed an activation of the P2X7 degenerative receptor induced by non-cytotoxic concentrations of forskolin from 1µM, demonstrating a placental toxicity of forskolin.…”

“…The choriocarcinoma-derived JEG-3 cell-line (ATCC HTB-36, Manassas, VA, USA), was selected based on the results of previous studies highlighting the use of these endocrine cells for placental toxicity studies [ 25 , 26 , 27 , 28 ]. JEG-3 cells were cultured in Minimum Essential Medium Eagle’s medium supplemented with 10% FBS, 2 mM of glutamine, 50 U/mL of penicillin and 50 µg/mL of streptomycin.…”

“…In our previous studies, we observed that the activation of the P2X7 membrane receptor is a marker of placental toxicity including endocrine-disrupting chemical-induced toxicity. Indeed, we highlighted the P2X7 receptor activation as a common mechanism of many endocrine-disrupting chemicals and suspected endocrine disrupting chemicals, including bisphenol A and diethylstilbestrol, in human placental cells [ 25 , 26 , 27 ].…”

Current Insights into Potential Effects of Micro-Nanoplastics on Human Health by in-vitro Tests

“…Currently, the toxicity of other alternative compounds of this group, such as bisphenol-F (BPF) and bisphenol-S (BPS), and 3,3′,5,5′-tetrabromobisphenol-A (TBBPA) that are also used as a flame retardant, are being investigated. Further, several studies have revealed that these compounds also presented toxicity in specific BPF and BPS ( Fouyet et al, 2021 ).…”

Evaluation of Placental Toxicity of Five Essential Oils and Their Potential Endocrine-Disrupting Effects

“…The hPlacentox assay, selected by the public–private PEPPER platform for the pre-validation of methods for endocrine disruptors characterization, is based on the human placental JEG-Tox cell model and allows the study of not only hormones disruption (both steroids and polypeptides), but also adverse health effects in the same cells [ 17 ], to meet WHO’s definition of EDCs [ 18 ]. Our previous studies in JEG-Tox cells showed that P2X7 receptor activation would be a common cellular mechanism of toxicity for EDCs in placenta [ 19 , 20 ]. P2X7 receptor activation is reported to be involved in multiple pathologies from immune disorders to degenerative diseases and placental disorders [ 21 , 22 , 23 , 24 , 25 ].…”