Cisplatin Induces Apoptosis in Mouse Neonatal Testes Organ Culture
Chemotherapy is used for childhood cancer but may lead to infertility in patients. Spermatogonia stem cells are present in the testes of prepubertal boys, although they do not produce sperm at this age. Herein, we evaluated the toxicity of cisplatin, a known medicine for cancer treatment, in neonata...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/13360 |
| _version_ | 1797467933239148544 |
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| author | Hyun-Jung Park Ji-Soo Kim Ran Lee Hyuk Song |
| author_facet | Hyun-Jung Park Ji-Soo Kim Ran Lee Hyuk Song |
| author_sort | Hyun-Jung Park |
| collection | DOAJ |
| description | Chemotherapy is used for childhood cancer but may lead to infertility in patients. Spermatogonia stem cells are present in the testes of prepubertal boys, although they do not produce sperm at this age. Herein, we evaluated the toxicity of cisplatin, a known medicine for cancer treatment, in neonatal mouse testes using in vitro organ culture. Mouse testicular fragments (MTFs) derived from 5.5-d postpartum mouse testes were exposed to 1–10 μg/mL cisplatin. The results showed that cisplatin significantly downregulated the expression of germ cell marker genes, including differentiated and undifferentiated, in a dose-dependent manner. In particular, a high dose of cisplatin (10 μg/mL) led to germ cell depletion. In addition, the expression levels of the Sertoli cell marker gene, the number of SOX9+ Sertoli cells, and the levels of SOX9 protein were markedly decreased in cisplatin-treated MTFs compared to controls. The mRNA expression of steroidogenic enzyme-related genes significantly increased in cisplatin-treated MTFs, except for estrogen receptor 1 (Esr1). Consistently, 3β-hydroxysteroid dehydrogenase protein was also observed in the interstitial regions of cisplatin-treated MTFs. Altogether, our findings showed a significant impairment in germ cell development, Sertoli cell survival, and steroidogenesis in the MTFs of cisplatin-treated mice. |
| first_indexed | 2024-03-09T18:59:47Z |
| format | Article |
| id | doaj.art-9db45ae3ca6a4199804040ecae1b599d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:59:47Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9db45ae3ca6a4199804040ecae1b599d2023-11-24T05:06:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123211336010.3390/ijms232113360Cisplatin Induces Apoptosis in Mouse Neonatal Testes Organ CultureHyun-Jung Park0Ji-Soo Kim1Ran Lee2Hyuk Song3Department of Stem Cell and Regenerative Biology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 05029, KoreaDepartment of Stem Cell and Regenerative Biology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 05029, KoreaDepartment of Stem Cell and Regenerative Biology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 05029, KoreaDepartment of Stem Cell and Regenerative Biology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 05029, KoreaChemotherapy is used for childhood cancer but may lead to infertility in patients. Spermatogonia stem cells are present in the testes of prepubertal boys, although they do not produce sperm at this age. Herein, we evaluated the toxicity of cisplatin, a known medicine for cancer treatment, in neonatal mouse testes using in vitro organ culture. Mouse testicular fragments (MTFs) derived from 5.5-d postpartum mouse testes were exposed to 1–10 μg/mL cisplatin. The results showed that cisplatin significantly downregulated the expression of germ cell marker genes, including differentiated and undifferentiated, in a dose-dependent manner. In particular, a high dose of cisplatin (10 μg/mL) led to germ cell depletion. In addition, the expression levels of the Sertoli cell marker gene, the number of SOX9+ Sertoli cells, and the levels of SOX9 protein were markedly decreased in cisplatin-treated MTFs compared to controls. The mRNA expression of steroidogenic enzyme-related genes significantly increased in cisplatin-treated MTFs, except for estrogen receptor 1 (Esr1). Consistently, 3β-hydroxysteroid dehydrogenase protein was also observed in the interstitial regions of cisplatin-treated MTFs. Altogether, our findings showed a significant impairment in germ cell development, Sertoli cell survival, and steroidogenesis in the MTFs of cisplatin-treated mice.https://www.mdpi.com/1422-0067/23/21/13360cisplatintestismeiosisgerm celloxygen stress |
| spellingShingle | Hyun-Jung Park Ji-Soo Kim Ran Lee Hyuk Song Cisplatin Induces Apoptosis in Mouse Neonatal Testes Organ Culture International Journal of Molecular Sciences cisplatin testis meiosis germ cell oxygen stress |
| title | Cisplatin Induces Apoptosis in Mouse Neonatal Testes Organ Culture |
| title_full | Cisplatin Induces Apoptosis in Mouse Neonatal Testes Organ Culture |
| title_fullStr | Cisplatin Induces Apoptosis in Mouse Neonatal Testes Organ Culture |
| title_full_unstemmed | Cisplatin Induces Apoptosis in Mouse Neonatal Testes Organ Culture |
| title_short | Cisplatin Induces Apoptosis in Mouse Neonatal Testes Organ Culture |
| title_sort | cisplatin induces apoptosis in mouse neonatal testes organ culture |
| topic | cisplatin testis meiosis germ cell oxygen stress |
| url | https://www.mdpi.com/1422-0067/23/21/13360 |
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