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Switching of mouse spermatogonial proliferation from the c-kit receptor-independent type to the receptor-dependent
Y Tajima1, K Sawada, T Morimoto
1Research Institute for Microbial Diseases, Osaka University, Japan.
Abstract:
Testicular cells composed mostly of germ cells and immature Sertoli cells from neonatal mice 2 and 5 days old were cultured to investigate germ-cell proliferation mediated by the c-kit receptor. The addition of antibody to block the interaction of the c-kit receptor with its ligand inhibited the proliferation of cultured spermatogonia from 5-day-old mice in a dose-dependent manner, but not from that of 2-day-old mice. The addition of anti-c-kit ACK2 monoclonal antibody also inhibited the proliferation of spermatogonia from 5-day-old mutant Sld/Sld mice but not of 5-day-old mutant Wv/Wv mice. The results indicate that c-kit-positive type A spermatogonia in the testes of 5-day-old mice require steel factor (kit ligand) for their proliferation, whereas self-renewal and differentiation of c-kit-negative primitive type A spermatogonia in the testes of 2-day-old mice do not.
Insights
Neonatal mouse testicular cells reveal that c-kit receptor signaling is crucial for spermatogonia proliferation in 5-day-old mice, but not in 2-day-old mice.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Cell Signaling
Background:
- Spermatogonia are crucial for male fertility, undergoing self-renewal and differentiation.
- The c-kit receptor and its ligand, steel factor, are implicated in germ cell development.
Purpose of the Study:
- To investigate the role of the c-kit receptor pathway in neonatal mouse spermatogonia proliferation.
- To determine the age-dependent requirement of c-kit signaling for germ cell development.
Main Methods:
- Primary culture of testicular cells from neonatal mice (2 and 5 days old).
- Inhibition of c-kit/steel factor interaction using blocking antibodies (ACK2).
- Analysis of spermatogonia proliferation in wild-type and mutant mice (Sld/Sld, Wv/Wv).
Main Results:
- Blocking c-kit signaling inhibited spermatogonia proliferation in 5-day-old mice but not in 2-day-old mice.
- This inhibition was observed in wild-type and Sld/Sld mutant mice, but not in Wv/Wv mutant mice.
- c-kit-positive spermatogonia in 5-day-old mice depend on steel factor for proliferation.
Conclusions:
- Steel factor (kit ligand) is essential for the proliferation of c-kit-positive type A spermatogonia in 5-day-old mice.
- c-kit-negative primitive type A spermatogonia in 2-day-old mice do not require c-kit signaling for self-renewal and differentiation.