Abstract
AbstractSpermatogonia, which produce sperm throughout the male lifetime, are regulated inside a niche composed of Sertoli cells, and other testis cell types. Defects in Sertoli cells often lead to infertility, but replacement of defective cells has been limited by the inability to deplete the existing population. Here, we use an FDA-approved non-toxic drug, benzalkonium chloride (BC), to deplete testis cell types in vivo. Four days after BC administration, Sertoli cells are preferentially depleted, and can be replaced to promote spermatogenesis from surviving (host) spermatogonia. Seven days after BC treatment, multiple cell types can be engrafted from fresh or cryopreserved testicular cells, leading to complete spermatogenesis from donor cells. These methods will be valuable for investigation of niche-supporting cell interactions, have the potential to lead to a therapy for idiopathic male infertility in the clinic, and could open the door to production of sperm from other species in the mouse.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference39 articles.
1. Flanagan, J. G., Chan, D. C. & Leder, P. Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant. Cell 64, 1025–1035 (1991).
2. Bashamboo, A. et al. Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1. Am. J. Hum. Genet. 87, 505–512 (2010).
3. Hiort, O. et al. Significance of mutations in the androgen receptor gene in males with idiopathic infertility. J. Clin. Endocrinol. Metab. 85, 2810–2815 (2000).
4. Ferlin, A. et al. Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations. Clin. Endocrinol. 65, 606–610 (2006).
5. Naughton, C. K., Jain, S., Strickland, A. M., Gupta, A. & Milbrandt, J. Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate. Biol. Reprod. 74, 314–321 (2006).
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