Bisphenol S and F affect cell cycle distribution and steroidogenic activity of human ovarian granulosa cells, but not primary granulosa tumour cells.
Autor: | Głód P; Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland; Doctoral School of Exact and Natural Sciences, Faculty of Biology, Institute of Zoology and Biomedical Sciences, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland., Borski N; Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland., Gogola-Mruk J; Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland., Opydo M; Department of Experimental Hematology, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Kraków, Poland., Ptak A; Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland. Electronic address: anna.ptak@uj.edu.pl. |
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Jazyk: | angličtina |
Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2023 Dec; Vol. 93, pp. 105697. Date of Electronic Publication: 2023 Sep 16. |
DOI: | 10.1016/j.tiv.2023.105697 |
Abstrakt: | Bisphenol S (BPS) and F (BPF), a new generation of bisphenols (BPs), are the main substitutes for bisphenol A (BPA). Both have been detected in human body fluids. Importantly, bisphenols are structurally similar to oestrogen, the main sex hormone in females. Because bisphenols bind to nuclear oestrogen receptors (ESR1 and ESR2) and to membrane G-coupled receptor 30 (GPR30), they can disrupt ovarian function. Here, we reveal the molecular mechanism underlying the effects of BPS and BPF on the cell cycle and steroidogenesis in the human ovarian granulosa cell (GC) line HGrC1. We show that BPS and BPF arrest GCs at the G0/G1 phase by inducing expression of cyclin D2, an important event that triggers maximal steroid synthesis in response to the BPS and BPF. We used pharmacological inhibitors to show that BPS and BPF, despite acting via already described pathways, also stimulate steroid secretion via IGF1R pathways in HGrC1 cells. Moreover, we identified differences critical to bisphenols response between normal (HGrC1) and primary tumour granulosa (COV434) cells, that enable COV434 cells to be more resistant to bisphenols. Overall, the data suggest that BPS and BPF drive steroidogenesis in human ovarian GCs by affecting the cell cycle. Furthermore, the results indicate that BPS and BPF act not only via the classical and non-classical ESR pathways, but also via the IGF1R pathway. Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Ptak reports financial support was provided by Jagiellonian University in Kraków. Anna Ptak reports a relationship with Jagiellonian University in Kraków that includes: employment. (Copyright © 2023 Elsevier Ltd. All rights reserved.) |
Databáze: | MEDLINE |
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