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Role of c-kit in mammalian spermatogenesis

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Abstract

The tyrosine-kinase receptor c-kit and its ligand, stem cell factor (SCF), are essential for the maintenance of primordial germ cells (PGCs) in both sexes. However, c-kit and a postmeiotic- specific alternative c-kit gene product play important roles also during post-natal stages of spermatogenesis. In the adult testis, the c-kit receptor is re-expressed in differentiating spermatogonia, but not in spermatogonial stem cells, whereas SCF is expressed by Sertoli cells under FSH stimulation. SCF stimulates DNA synthesis in type A spermatogonia cultured in vitro, and injection of anti-c-kit antibodies blocks their proliferation in vivo. A point mutation in the c-kit gene, which impairs SCF-mediated activation of phosphatydilinositol 3-kinase, does not cause any significant reduction in PGCs number during embryonic development, nor in spermatogonial stem cell populations. However males are completely sterile due to a block in the initial stages of spermatogenesis, associated to abolishment of DNA-synthesis in differentiating A1-A4 spermatogonia. With the onset of meiosis c-kit expression ceases, but a truncated c-kit product, tr-kit, is specifically expressed in post-meiotic stages of spermatogenesis, and is accumulated in mature spermatozoa. Microinjection of tr-kit into mouse eggs causes their parthenogenetic activation, suggesting that it might play a role in the final function of the gametes, fertilization.

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  1. Dipartimento di Sanità Pubblica e Biologia Cellulare, Sezione di Anatomia, Università “Tor Vergata”, Via O. Raimondo 8, 00173, Roma, Italy

    P. Rossi, C. Sette, S. Dolci & R. Geremia

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  1. P. Rossi
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  2. C. Sette
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  3. S. Dolci
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  4. R. Geremia
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Correspondence to P. Rossi.

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Rossi, P., Sette, C., Dolci, S. et al. Role of c-kit in mammalian spermatogenesis. J Endocrinol Invest 23, 609–615 (2000). https://doi.org/10.1007/BF03343784

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