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Eif2s3y Promotes the Proliferation of Spermatogonial Stem Cells by Activating ERK Signaling
Mengfei Zhang1, Na Li1, Wenqing Liu1
1College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Abstract:
The future fertility of males with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Spermatogonial stem cell transplantation is believed to be a way to restore fertility in men. However, the survival efficiency of transplanted cells is still low. Eukaryotic translation initiation factor 2 subunit 3 and structural gene Y-linked (Eif2s3y) located on the Y chromosome of male animals is a coding gene of eIF2γ which mainly functions in translation initiation. Recently, the emerging role of Eif2s3y in spermatogenesis has been emphasized in several studies. However, the underlying mechanism is still unclear. In addition, how Eif2s3y functions in large animals remains largely unknown. In this study, we obtained the CDS sequence of the Eif2s3y gene from the testis of dairy goats and found that this gene was highly expressed in the testis and was evolutionarily conserved among different species. Interestingly, overexpression of Eif2s3y promoted the proliferation of spermatogonial stem cells of dairy goats by activating the ERK signaling pathway. In animal experiments, overexpressing Eif2s3y promoted transplanted goat spermatogonial stem cells and produced more colonies after microinjection into the seminiferous tubules of infertile mice. In conclusion, our study highlights an undiscovered role of Eif2s3y in dairy goat reproduction. This finding may provide an important basis for future works regarding male spermatogenic cell restoration and represent a major advance toward surrogate sires becoming a tool for disseminating and regenerating germplasm in all mammals.
Insights
Restoring male fertility after cancer treatment is crucial. This study found that overexpressing the Eif2s3y gene promotes spermatogonial stem cell proliferation and survival, offering a new path for fertility restoration in dairy goats and potentially other mammals.
Area of Science:
- Reproductive Biology
- Molecular Genetics
- Cell Biology
Background:
- Cancer treatments like chemotherapy and radiotherapy can impair male fertility.
- Spermatogonial stem cell transplantation is a promising fertility restoration method, but cell survival remains a challenge.
- The role of Eukaryotic translation initiation factor 2 subunit 3 and structural gene Y-linked (Eif2s3y) in spermatogenesis, especially in large animals, is not well understood.
Purpose of the Study:
- To investigate the function of the Eif2s3y gene in dairy goat spermatogenesis.
- To explore the potential of Eif2s3y in enhancing spermatogonial stem cell proliferation and transplantation efficiency.
- To elucidate the molecular mechanism by which Eif2s3y influences male fertility.
Main Methods:
- Obtained the CDS sequence of the Eif2s3y gene from dairy goat testes.
- Analyzed Eif2s3y expression in testes and its evolutionary conservation.
- Overexpressed Eif2s3y in dairy goat spermatogonial stem cells and assessed proliferation.
- Investigated the involvement of the ERK signaling pathway.
- Evaluated the effect of overexpressing Eif2s3y on transplanted goat spermatogonial stem cells in infertile mice.
Main Results:
- The Eif2s3y gene is highly expressed in dairy goat testes and is evolutionarily conserved.
- Overexpression of Eif2s3y significantly promoted the proliferation of dairy goat spermatogonial stem cells.
- Eif2s3y overexpression activated the ERK signaling pathway in spermatogonial stem cells.
- Transplanted goat spermatogonial stem cells overexpressing Eif2s3y showed enhanced survival and colony formation in infertile mice.
Conclusions:
- Eif2s3y plays a crucial role in promoting dairy goat spermatogonial stem cell proliferation and survival.
- Activating the ERK signaling pathway is a key mechanism for Eif2s3y's function in spermatogenesis.
- Eif2s3y holds significant potential for improving spermatogonial stem cell transplantation efficiency for male fertility restoration.
- This research provides a foundation for utilizing Eif2s3y in reproductive technologies, including the development of surrogate sires for germplasm regeneration.
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