Bisphenol Analogs Downregulate the Self-Renewal Potential of Spermatogonial Stem Cells
Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol- S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. Materials and Methods: SSCs enriched from 6- to 8...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Korean Society for Sexual Medicine and Andrology
2025-01-01
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| Series: | The World Journal of Men's Health |
| Subjects: | |
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| Summary: | Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-
S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models.
Materials and Methods: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations
of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized
flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The
functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in
vivo transplantation and subsequent testis analysis.
Results: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition
of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF,
it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction
in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce
a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced
by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and
BPS may not adversely affect the spermatogenesis.
Conclusions: Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs,
similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts
on male fertility. |
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| ISSN: | 2287-4208 2287-4690 |