Sex-specific effects of bisphenol A, its substitutes and benzophenone-3 on T helper 1 cell differentiation
Year: 2024
Type: dissertation
Abstract: Background: T cells, known to play a pivotal role in the development of a plethora of diseases, may represent as a target of endocrine disrupting chemicals (EDCs). Moreover, there is accumulating evidence that endocrine-immune interactions show some sex-specificity. Objectives: We aimed to study the influence of various EDCs, namely different bisphenols and benzophenone-3 in single and mixed exposure scenarios on T helper 1 (Th1) cell differentiation in a sex-specific approach. Methods: Naïve CD4+ T cells were isolated from mouse lymphoid organs or from human peripheral blood of both sexes. A specific cytokine cocktail and T cell receptor stimulants were added to naïve T cell cultures to induce Th1 cell differentiation. Treatment with different concentrations of bisphenol A (BPA; 0,01-100µM), its analogs (BPF, BPS; 0,01-100µM) and benzophenone-3 (BP-3; 0,001-10µM) started 24 hours after T cell differentiation and lasted for another 72 hours. Flow cytometry analyses were applied for detecting changes in cell viability and expression of Th-subset-specific transcriptional factors and cytokines. Data was analyzed with GraphPad Prism after extracting with Flowjo software. Results: Cell viability was compromised when mouse female T cells were exposed to the highest BPA and BPS concentration (100 µM each) The sub-highest concentration of BPA (10 µM) affected Th1 differentiation in mouse female T cells. For the mixtures, the presence of the 100 µM BPA in combination with all tested BP-3 concentrations showed an inhibitory effect on human Th1 differentiation among both sexes. Moreover, several BPA-BP-3 combinations impaired mouse male Th1 cell differentiation but did not affect mouse female T cells. Conclusion: Our research indicates that high concentrations of BPA impair the cell viability of mouse Th1 cells. When used in combination, high concentrations of BP-3, with the assistance of BPA, impair the expression of cytokine in Th1, Th17, and Treg cells in female mice, as well as female Treg cells. This phenomenon exhibits sex specificity.
Author: Yin, Ziran
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7043289627