Abstract
In mice the chemokine Cxcl12 and its receptor Cxcr4 participate in maintenance of the spermatogonial population during postnatal development. More complexity arises since Cxcl12 also binds to the non-classical/atypical chemokine receptor Cxcr7. We explored the expression pattern of Cxcl12, Cxcr4 and Cxcr7 during postnatal development in mouse testes and investigated the response of Cxcl12, Cxcr4, Cxcr7 and SSC-niche associated factors to busulfan-induced germ cell depletion and subsequent recovery by RNA expression analysis and localization of the proteins. In neonatal testes transcript levels of Cxcl12, Cxcr4 and Cxcr7 were relatively low and protein expression of Cxcr7 was restricted to gonocytes and spermatogonia. During development, RNA expression of Cxcl12 remained stable but that of Cxcr4 and Cxcr7 increased. Cxcr7 was expressed in germ cells located at the basement membrane of the seminiferous tubules. In adult testes, transcript levels of Cxcl12 were highest while the localization of Cxcr7 did not change. Following germ cell depletion, a significantly increased expression of Cxcl12 and a decreased expression of Cxcr7 were observed. Germ cells repopulating the seminiferous tubules were immunopositive for Cxcr7. We conclude that Cxcr7 expression to be restricted to premeiotic germ cells throughout postnatal testicular development and during testicular recovery. Hence, the spermatogonial population may not only be simply controlled by interaction of Cxcl12 with Cxcr4 but may also involve Cxcr7 as an important player.
Highlights
In mammalian testes, the unipotent spermatogonial stem cells (SSCs) reside within specialized microenvironments called ‘niches’, essential for the regulation of stem cell self-renewal and differentiation
It has been experimentally shown by germ cell transplantation experiments, that in congenitally infertile W/Wv mouse testes an increased expression of Cxcl12 by Sertoli cells leads to an elevated/ enhanced colonization of seminiferous tubules by Cxcr4 positive SSCs
Transcript levels of the chemokine Cxcl12 per testis remained constant from birth until day 21 and increased only in adult animals (4-fold, Fig. 1B). mRNA levels of the chemokine receptors Cxcr4 (Fig. 1C) and Cxcr7 (Fig. 1D) were low at birth and increased on day 21 pp and in adult animals (.37 days dpp), respectively
Summary
The unipotent spermatogonial stem cells (SSCs) reside within specialized microenvironments called ‘niches’, essential for the regulation of stem cell self-renewal and differentiation. The functional role of the Cxcl12/Cxcr interaction within the adult mouse testis has been investigated in vitro and it was suggested that the ligand/receptor pair is involved in SSC propagation but prevents SSC differentiation [15]. It has been experimentally shown by germ cell transplantation experiments, that in congenitally infertile W/Wv mouse testes an increased expression of Cxcl by Sertoli cells leads to an elevated/ enhanced colonization of seminiferous tubules by Cxcr positive SSCs. In addition, it has been experimentally shown by germ cell transplantation experiments, that in congenitally infertile W/Wv mouse testes an increased expression of Cxcl by Sertoli cells leads to an elevated/ enhanced colonization of seminiferous tubules by Cxcr positive SSCs Based on these studies it was concluded that the Cxcr mediated action of Cxcl plays a role for the homing and colonization process of SSCs into their niches [14, 15]. The interaction between Cxcl and Cxcr is required for the migration as well as for the maintenance of primordial germ cells (PGCs) in mice [19, 20]
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