1. Academic Validation
  2. Deficiency in the Rab25 gene leads to a decline in male fertility and testicular injury: Impact on the regulation of germ cell proliferation and apoptosis

Deficiency in the Rab25 gene leads to a decline in male fertility and testicular injury: Impact on the regulation of germ cell proliferation and apoptosis

  • Exp Cell Res. 2024 Oct 1;442(2):114285. doi: 10.1016/j.yexcr.2024.114285.
Qiang Zhang 1 Zhicheng Zhang 1 Zhenmin Liu 1 Chong Wang 1 Hongsong Chen 1 Lianju Shen 1 Chunlan Long 1 Guanghui Wei 1 Xing Liu 2
Affiliations

Affiliations

  • 1 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, 400014, China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
  • 2 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, 400014, China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. Electronic address: liux@hospital.cqmu.edu.cn.
Abstract

Background: Rab25 is a member of the Rab family, functioning as a regulatory molecule in intracellular transport. Although its involvement in cellular functions and disease development is well-established, its precise roles in male reproductive physiology remain elusive.

Methods: To explore the specific roles of Rab25 in testicular development and spermatogenesis, we established the Rab25-/- mouse model and Rab25 knockdown germ cell line (GC-2). We compared the fertility, sperm analysis, and testicular tissues between Rab25-/- and wild-type male mice. To delve deeper into potential mechanisms, we employed immunohistochemistry, TUNEL assay, Western Blotting, CCK-8 assay, etc. to evaluate cell proliferation and Apoptosis in testicular tissues and GC-2 cells.

Results: Our findings indicated that Rab25 was expressed in germ cells and Leydig cells in the testes. Although the weight of Rab25-/- mice testes exhibited no significant changes, fertility was compromised, with a decrease in sperm quantity and reduced motility. HE staining revealed a disorganized arrangement of germ cells and vacuolization. Additionally, chromatin marginalization and nuclear pyknosis were observed in the Rab25-/- mice. In both Rab25-/- mice testes and Rab25 knockdown GC-2 cells, we found that germ cell proliferation was reduced, while Apoptosis was increased.

Conclusions: In conclusion, our study proposes that Rab25 plays a vital role in spermatogenesis by regulating the proliferation and Apoptosis of germ cells.

Keywords

Gene knockout; Male fertility; Rab25; Spermatogenesis; Testis.

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