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. 2024 Oct 1;442(2):114285.
doi: 10.1016/j.yexcr.2024.114285. Epub 2024 Oct 17.

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

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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

Qiang Zhang et al. Exp Cell Res. .

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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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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