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Background <p>Pelvic irradiation is widely used in cancer therapy but frequently damages non-cancerous tissues, particularly the highly proliferative spermatogenic cells of the testes, leading to infertility. Endoplasmic reticulum (ER) stress and apoptosis are key mechanisms underlying radiation-induced germ cell loss. Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, has been reported to exert cytoprotective effects in testicular injury models by suppressing ER stress.</p> Objectives <p>This study aimed to evaluate the protective role of TUDCA against radiation-induced testicular dysfunction in mice, with a specific focus on its ability to inhibit germ cell apoptosis and modulate ER stress–related pathways.</p> Results <p>At 12 h after irradiation, TUDCA administration significantly reduced germ cell apoptosis. By 30 days post-irradiation, TUDCA-treated mice exhibited increased testis weight compared with irradiated controls. Histological analyses revealed improvements in seminiferous tubule diameter and epithelial height, alongside higher seminiferous tubule repopulation and stem cell survival indices. In the epididymis, TUDCA prevented the radiation-induced decline in sperm count and motility. Molecular analysis showed that irradiation elevated <i>Ddit3 </i>(CHOP) and <i>Atf6</i> expression, whereas TUDCA markedly suppressed these ER stress markers.</p> Conclusion <p>TUDCA effectively protects the testes from radiation-induced injury by reducing germ cell apoptosis, maintaining testicular architecture, preserving sperm function, and attenuating ER stress signaling. These findings suggest that TUDCA has potential as a therapeutic agent to prevent male infertility following pelvic irradiation.</p>

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Protective effect of administered TUDCA against radiation-induced testicular injury in mice

  • 期刊论文

  • 发表日期：

    2026年6月17日

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  • Sohee Jeong,
  • Min Ji Bae,
  • Chang Geun Lee,
  • Wol Soon Jo,
  • Yeong-Rok Kang,
  • Ju Won Choi,
  • Jeongmin Lee,
  • Changjong Moon,
  • Min Ho Jeong,
  • Hyun Seok Choi,
  • Jeong-Hwa Baek,
  • Joong Sun Kim

摘要

Background

Pelvic irradiation is widely used in cancer therapy but frequently damages non-cancerous tissues, particularly the highly proliferative spermatogenic cells of the testes, leading to infertility. Endoplasmic reticulum (ER) stress and apoptosis are key mechanisms underlying radiation-induced germ cell loss. Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, has been reported to exert cytoprotective effects in testicular injury models by suppressing ER stress.

Objectives

This study aimed to evaluate the protective role of TUDCA against radiation-induced testicular dysfunction in mice, with a specific focus on its ability to inhibit germ cell apoptosis and modulate ER stress–related pathways.

Results

At 12 h after irradiation, TUDCA administration significantly reduced germ cell apoptosis. By 30 days post-irradiation, TUDCA-treated mice exhibited increased testis weight compared with irradiated controls. Histological analyses revealed improvements in seminiferous tubule diameter and epithelial height, alongside higher seminiferous tubule repopulation and stem cell survival indices. In the epididymis, TUDCA prevented the radiation-induced decline in sperm count and motility. Molecular analysis showed that irradiation elevated Ddit3 (CHOP) and Atf6 expression, whereas TUDCA markedly suppressed these ER stress markers.

Conclusion

TUDCA effectively protects the testes from radiation-induced injury by reducing germ cell apoptosis, maintaining testicular architecture, preserving sperm function, and attenuating ER stress signaling. These findings suggest that TUDCA has potential as a therapeutic agent to prevent male infertility following pelvic irradiation.