Abstract
Spermatogonia, 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.
Highlights
Spermatogonia, which produce sperm throughout the male lifetime, are regulated inside a niche composed of Sertoli cells, and other testis cell types
The efficient production of sperm from spermatogonia requires the coordinated interplay between germ cells and various somatic support cells making up the spermatogenic niche
A solution of 0.02% benzalkonium chloride (BC) completely eliminated Sertoli cells in 82% of the tubule cross-sections analyzed (719/873 tubule sections, n = 4 independent testes), while fewer Sertoli cells were left in the remainder (952 cells/154 tubule sections; ~6 cells/tubule section; n = 4 independent testes) compared with control (3070 cells/115 tubule sections; ~27 cells/ tubule section; n = 4 independent testes) (P = 0.029)
Summary
Spermatogonia, which produce sperm throughout the male lifetime, are regulated inside a niche composed of Sertoli cells, and other testis cell types. 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. At later times after BC treatment, some germ cell and stromal support cell types are lost, most likely secondary to the loss of the trophic support of Sertoli cells These cells can be replaced by engraftment of fresh or cryopreserved testicular cells, leading to recovery of spermatogenesis from donor cells
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