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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| Format: | Article |
| Language: | English |
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Korean Society for Sexual Medicine and Andrology
2025-01-01
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| Series: | The World Journal of Men's Health |
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| author | Seo-Hee Kim Seung Hee Shin Seok-Man Kim Sang-Eun Jung Beom-Jin Shin Jin Seop Ahn Kyoung Taek Lim Dong-Hwan Kim Kichoon Lee Buom-Yong Ryu |
| author_facet | Seo-Hee Kim Seung Hee Shin Seok-Man Kim Sang-Eun Jung Beom-Jin Shin Jin Seop Ahn Kyoung Taek Lim Dong-Hwan Kim Kichoon Lee Buom-Yong Ryu |
| author_sort | Seo-Hee Kim |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-63db50ad9494453ab40859e99540e837 |
| institution | Kabale University |
| issn | 2287-4208 2287-4690 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Korean Society for Sexual Medicine and Andrology |
| record_format | Article |
| series | The World Journal of Men's Health |
| spelling | doaj-art-63db50ad9494453ab40859e99540e8372025-01-03T03:29:02ZengKorean Society for Sexual Medicine and AndrologyThe World Journal of Men's Health2287-42082287-46902025-01-0143115416510.5534/wjmh.230166Bisphenol Analogs Downregulate the Self-Renewal Potential of Spermatogonial Stem CellsSeo-Hee Kim0https://orcid.org/0000-0002-4867-0519Seung Hee Shin1https://orcid.org/0009-0008-3566-3185Seok-Man Kim2https://orcid.org/0000-0003-1939-2553Sang-Eun Jung3https://orcid.org/0000-0003-1153-2195Beom-Jin Shin4https://orcid.org/0009-0007-2769-4355Jin Seop Ahn5https://orcid.org/0000-0001-9244-0561Kyoung Taek Lim6https://orcid.org/0009-0003-9084-0387Dong-Hwan Kim7https://orcid.org/0000-0002-3993-4025Kichoon Lee8https://orcid.org/0000-0001-6169-7516Buom-Yong Ryu9https://orcid.org/0000-0002-8349-7299Department of Animal Science and Technology, Chung-Ang University, AnseongDepartment of Animal Science and Technology, Chung-Ang University, AnseongDepartment of Animal Science and Technology, Chung-Ang University, AnseongDepartment of Animal Science and Technology, Chung-Ang University, AnseongDepartment of Animal Science and Technology, Chung-Ang University, AnseongDepartment of Animal Science and Technology, Chung-Ang University, AnseongDepartment of Urology, Maria Fertility Hospital, SeoulDepartment of Animal Sciences, The Ohio State University, Columbus, OHDepartment of Animal Sciences, The Ohio State University, Columbus, OHDepartment of Animal Science and Technology, Chung-Ang University, AnseongPurpose: 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.bisphenol abisphenol fbisphenol smale fertilityself-renewalspermatogonial stem cells |
| spellingShingle | Seo-Hee Kim Seung Hee Shin Seok-Man Kim Sang-Eun Jung Beom-Jin Shin Jin Seop Ahn Kyoung Taek Lim Dong-Hwan Kim Kichoon Lee Buom-Yong Ryu Bisphenol Analogs Downregulate the Self-Renewal Potential of Spermatogonial Stem Cells The World Journal of Men's Health bisphenol a bisphenol f bisphenol s male fertility self-renewal spermatogonial stem cells |
| title | Bisphenol Analogs Downregulate the Self-Renewal Potential of Spermatogonial Stem Cells |
| title_full | Bisphenol Analogs Downregulate the Self-Renewal Potential of Spermatogonial Stem Cells |
| title_fullStr | Bisphenol Analogs Downregulate the Self-Renewal Potential of Spermatogonial Stem Cells |
| title_full_unstemmed | Bisphenol Analogs Downregulate the Self-Renewal Potential of Spermatogonial Stem Cells |
| title_short | Bisphenol Analogs Downregulate the Self-Renewal Potential of Spermatogonial Stem Cells |
| title_sort | bisphenol analogs downregulate the self renewal potential of spermatogonial stem cells |
| topic | bisphenol a bisphenol f bisphenol s male fertility self-renewal spermatogonial stem cells |
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