A revised model for spermatogonial expansion in man: lessons from non-human primates

Ehmcke, Jens; Schlatt, Stefan

doi:10.1530/rep.1.01081

Cited by 157 publications

(94 citation statements)

References 46 publications

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“…The full time course of the pubertal increase in undifferentiated spermatogonial number remains to be determined because a late pubertal group was not included in this study. Considerable controversy surrounds the issue of the mitotic behavior of Ad dark spermatogonia (Ehmcke & Schlatt 2006, Hermann et al 2010, Plant 2010. In the adult, classic studies on the monkey testis conducted in the 1960s led Clermont (1972) to propose that these cells very rarely divide and he therefore tentatively termed them reserve stem cells.…”

Section: Late Juvenilementioning

confidence: 99%

Sertoli cell differentiation in rhesus monkey (Macaca mulatta) is an early event in puberty and precedes attainment of the adult complement of undifferentiated spermatogonia

Simorangkir

Ramaswamy²,

Marshall³

et al. 2012

Reproduction

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In primates, the time course of Sertoli cell proliferation and differentiation during puberty and its relationship with the expansion of undifferentiated type A spermatogonia that occurs at this critical stage of development are poorly defined. Mid and late juvenile and early and late pubertal male rhesus monkeys were studied. Testes were immersion fixed, embedded in paraffin, and sectioned at 5 mm. Sertoli cell number per testis, S-phase labeling (BrdU), and growth fraction (Ki67 labeling) were determined and correlated with corresponding parameters for undifferentiated type A spermatogonia (A dark and A pale). Dual fluorescence labeling was used in addition to histochemistry to monitor spermatogonial differentiation during the peripubertal period using GFRa-1 and cKIT as markers. While the adult complement of Sertoli cells/testis was attained in early pubertal monkeys after only a few weeks of exposure to the elevated gonadotropin secretion characteristic of this developmental stage, the number of undifferentiated type A spermatogonia several months later in mid pubertal monkeys was only 50% of that in adult testes. Both A dark and A pale spermatogonia exhibited high S-phase BrdU labeling at all stages of juvenile and pubertal development. Spermatogonial differentiation, as reflected histochemically and by relative changes in GFRa-1 and cKIT expression, was not observed until after the initiation of puberty. In the rhesus monkey and maybe in other higher primates including human, the pubertal proliferation of undifferentiated spermatogonia is insidious and proceeds in the wake of a surge in Sertoli cell proliferation following termination of the juvenile stage of development.

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Section: Late Juvenilementioning

confidence: 99%

Sertoli cell differentiation in rhesus monkey (Macaca mulatta) is an early event in puberty and precedes attainment of the adult complement of undifferentiated spermatogonia

Simorangkir

Ramaswamy²,

Marshall³

et al. 2012

Reproduction

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“…Clermont (1972) claimed that the Ad and Ap spermatogonia represent 'reserve' and 'active' stem cells respectively. Others proposed that the low mitotic index of the Ad spermatogonia is indicative of a 'true' stem cell phenotype (for review, see Dadoune (2007)) while the regularly dividing Ap spermatogonia may represent 'renewing progenitors' (compare Ehmcke & Schlatt (2006)). Different from these suggestions, a study in the rhesus monkey indicated that the Ad and Ap nuclear phenotypes of primate spermatogonia may rather correlate with different stages of the cell cycle (i.e.…”

Section: Introductionmentioning

confidence: 99%

Differential marker protein expression specifies rarefaction zone-containing human Adark spermatogonia

Kopylow¹,

Staege²,

Spiess³

et al. 2012

Reproduction

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It is unclear whether the distinct nuclear morphologies of human A dark (Ad) and A pale (Ap) spermatogonia are manifestations of different stages of germ cell development or phases of the mitotic cycle, or whether they may reflect still unknown molecular differences. According to the classical description by Clermont, human dark type A spermatogonium (Ad) may contain one, sometimes two or three nuclear 'vacuolar spaces' representing chromatin rarefaction zones. These structures were readily discerned in paraffin sections of human testis tissue during immunohistochemical and immunofluorescence analyses and thus represented robust morphological markers for our study. While a majority of the marker proteins tested did not discriminate between spermatogonia with and without chromatin rarefaction zones, doublesex-and mab-3-related transcription factor (DMRT1), tyrosine kinase receptor c-Kit/CD117 (KIT) and proliferation-associated antigen Ki-67 (KI-67) appeared to be restricted to subtypes which lacked the rarefaction zones. Conversely, exosome component 10 (EXOSC10) was found to accumulate within the rarefaction zones, which points to a possible role of this nuclear domain in RNA processing.

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“…However, for these possibilities to be realised, new differentiation protocols will have to be developed and ways found to prevent the formation of teratomas. In addition, spermatogonial multiplication and stem cell renewal in primates differ from those in non-primate mammals and are not yet fully understood (de Rooij and Russell, 2000;Ehmcke and Schlatt, 2006). Human SSCs might be different in nature and might be regulated in different ways, and they might also have different levels of susceptibility to making the transition to an ES-like cell.…”

Section: Discussionmentioning

confidence: 99%

Deriving multipotent stem cells from mouse spermatogonial stem cells: a new tool for developmental and clinical research

Rooij

Mizrak

2008

Development

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In recent years, embryonic stem (ES) cell-like cells have been obtained from cultured mouse spermatogonial stem cells (SSCs). These advances have shown that SSCs can transition from being the stem cell-producing cells of spermatogenesis to being multipotent cells that can differentiate into derivatives of all three germ layers. As such, they offer new possibilities for studying the mechanisms that regulate stem cell differentiation. The extension of these findings to human SSCs offers a route to obtaining personalized ES-like or differentiated cells for use in regenerative medicine. Here, we compare the different approaches used to derive ES-like cells from SSCs and discuss their importance to clinical and developmental research.

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A revised model for spermatogonial expansion in man: lessons from non-human primates

Cited by 157 publications

References 46 publications

Sertoli cell differentiation in rhesus monkey (Macaca mulatta) is an early event in puberty and precedes attainment of the adult complement of undifferentiated spermatogonia

Sertoli cell differentiation in rhesus monkey (Macaca mulatta) is an early event in puberty and precedes attainment of the adult complement of undifferentiated spermatogonia

Differential marker protein expression specifies rarefaction zone-containing human Adark spermatogonia

Deriving multipotent stem cells from mouse spermatogonial stem cells: a new tool for developmental and clinical research

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