Title The Luteinizing Hormone-Testosterone Pathway Regulates Mouse Spermatogonial Stem Cell Self-Renewal by Suppressing WNT5A Expression in Sertoli Cells
نویسندگان
چکیده
SUMMARY Spermatogenesis originates from self-renewal of spermatogonial stem cells (SSCs). Previous studies have reported conflicting roles of gonadotropic pituitary hormones in SSC self-renewal. Here, we explored the role of hormonal regulation of SSCs using Fshb and Lhcgr knockout (KO) mice. Although follicle-stimulating hormone (FSH) is thought to promote self-renewal by glial cell line-derived neurotro-phic factor (GDNF), no abnormalities were found in SSCs and their microenvironment. In contrast, SSCs were enriched in Lhcgr-deficient mice. Moreover, wild-type SSCs transplanted into Lhcgr-deficient mice showed enhanced self-renewal. Microarray analysis revealed that Lhcgr-deficient testes have enhanced WNT5A expression in Sertoli cells, which showed an immature phenotype. Since WNT5A was upregulated by anti-androgen treatment, testosterone produced by luteinizing hormone (LH) is required for Sertoli cell maturation. WNT5A promoted SSC activity both in vitro and in vivo. Therefore, FSH is not responsible for GDNF regulation, while LH negatively regulates SSC self-renewal by suppressing WNT5A via testosterone.
منابع مشابه
The Luteinizing Hormone-Testosterone Pathway Regulates Mouse Spermatogonial Stem Cell Self-Renewal by Suppressing WNT5A Expression in Sertoli Cells
Spermatogenesis originates from self-renewal of spermatogonial stem cells (SSCs). Previous studies have reported conflicting roles of gonadotropic pituitary hormones in SSC self-renewal. Here, we explored the role of hormonal regulation of SSCs using Fshb and Lhcgr knockout (KO) mice. Although follicle-stimulating hormone (FSH) is thought to promote self-renewal by glial cell line-derived neuro...
متن کاملWnt5a is a cell-extrinsic factor that supports self-renewal of mouse spermatogonial stem cells.
The maintenance of spermatogonial stem cells (SSCs) provides the foundation for life-long spermatogenesis. Although glial-cell-line-derived neurotrophic factor and fibroblast growth factor 2 are crucial for self-renewal of SSCs, recent studies have suggested that other growth factors have important roles in controlling SSC fate. Because β-catenin-dependent Wnt signaling promotes self-renewal of...
متن کاملنقش سلولهای سرتولی در تعیین سرنوشت سلولهای بنیادی اسپرماتوگونی
Background: Spermatogenesis is a complex and highly organized process of proliferation and differentiation of spermatogonial stem cells. Spermatogonial stem cells (SSCs) as a unique stem cell have the potential to self-renewal, differentiation and transmit genetic information to the next generation and play a vital role in maintaining fertility. Sertoli cells as the only somatic cells within th...
متن کاملEvaluation and Comparison of the Expression Levels of the ZBTB16 (Plzf) and ZFP Genes and Alkaline Phosphatase in Three Cell Populations: Mouse Spermatogonial Stem Cells, Embryonic Stem-Like Cells (Es-Like), And Embryonic Stem Cells
Introduction: One of the vital enzymes during spermatogenesis, which is one of the pluripotency factors of stem cells and contributes to maintaining their pluripotency is alkaline phosphatase. ZBTB16 and ZFP proteins are critical elements in stem cells which are expressed in pluripotent stem cells and maintain their pluripotency due to their role in messaging pathways. Material & Methods: The ...
متن کامل