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Expression of pluripotency marker, UTF1, is restricted to a subpopulation of early A spermatogonia in rat testis

Department of Endocrinology and Metabolism, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
Reproduction 08/2008; 136(1):33-40. DOI: 10.1530/REP-07-0536
Source: PubMed

ABSTRACT The population of early A spermatogonia includes stem cells that possess spermatogonial stem cell properties. Recent reports suggest that these cells have the ability to regain pluripotent properties. Here, we show that expression of the pluripotency marker undifferentiated embryonic cell transcription factor 1 (UTF1) is restricted to distinct germ cells within the testis. In embryonic and neonatal testes, all gonocytes were found to strongly express UTF1. During further testicular development, expression of UTF1 was restricted to a subset of A spermatogonia and with the increase in age the number of cells expressing UTF1 decreased even more. Ultimately, in the adult rat testis, only a small subset of the A spermatogonia expressed UTF1. Remarkably, even in testes of vitamin A-deficient rats, in which the early A spermatogonia (A(s), A(pr), and A(al)) are the only type of spermatogonia, only a subset of the spermatogonia expressed UTF1. In the adult rat testis, expression of UTF1 is restricted to a subpopulation of the ZBTB16 (PLZF)-positive early A spermatogonia. Furthermore, the observed distribution pattern of UTF1-expressing cells over the different stages of the cycle of the seminiferous epithelium suggests that the expression of UTF1 is restricted to those A(s), A(pr), and short chains of A(al) spermatogonia that are in the undifferentiated state and therefore maintain the ability to differentiate into A1 spermatogonia in the next round of the epithelial cycle or possibly even in other directions when they are taken out of their testicular niche.

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Available from: B. J. L. Eggen, Dec 09, 2014
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    • "In rats, UTF1 expression is evident in all gonocytes in embryonic and neonatal testes, although restricted to the small subpopulation of the spermatogonia A during testicular development [10]. Previous studies have suggested that UTF1 is a conserved molecule of undifferentiated spermatogonia and might play critical roles in the self-renewal of SSCs in mammals [9], [10]. The main purposes of this study are: 1) to determine the changes in the expression pattern of UTF1 at various reproductive stages in stallions, 2) to identify subpopulations of spermatogonia that express UTF1. "
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    ABSTRACT: Spermatogonial stem cells (SSCs) continuously undergo self-renewal and differentiation to sustain spermatogenesis throughout adulthood in males. In stallions, SSCs may be used for the production of progeny from geldings after cryopreservation and therapy for infertile and subfertile stallions. Undifferentiated cell transcription factor 1 (UTF1) is a putative marker for undifferentiated spermatogonia in humans and rats. The main purposes of this study are to determine the following: 1) changes in the expression pattern of UTF1 at various reproductive stages of stallions, 2) subpopulations of spermatogonia that express UTF1. Testicular samples were collected and categorized based on the age of the horses as follows: pre-pubertal (<1 yr), pubertal (1-1.5 yr), post-pubertal (2-3 yr), and adult (4-8 yr). Western blot analysis was utilized to determine the cross-activity of the UTF1 antibody to horse testes tissues. Immunohistochemistry was conducted to investigate the UTF1 expression pattern in germ cells at different reproductive stages. Whole mount staining was applied to determine the subpopulation of UTF1-positive spermatogonia. Immunohistological analysis showed that most germ cells in the pre-pubertal and pubertal stages were immunolabeled with UTF1, whereas only a few germ cells in the basal compartment of the seminiferous tubule cross-sections of post-pubertal and adult tissues were UTF1-positive. No staining was observed in the Sertoli or Leydig cells at any reproductive stages. Whole mount staining showed that As, Apr, and chains of 4, 8, 16 Aal spermatogonia were immunolabeled with UTF1 in the post-pubertal stallion tubule. Isolated single germ cells were also immunolabeled with UTF1. In conclusion, UTF1 is expressed in undifferentiated spermatogonia, and its antibody can be used as a putative marker for SSCs in stallions.
    PLoS ONE 10/2014; 9(10):e108825. DOI:10.1371/journal.pone.0108825 · 3.23 Impact Factor
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    • "Very impressively, under these special circumstances, a significant fraction of germ cells in the hamster as well as in the NHP testis were LIN28-positive as evidenced by staining of the same samples for the general germ cell marker VASA. UTF-1 is an established spermatogonial marker in human and rat testis (van Bragt et al., 2008; von Kopylow et al., 2010). UTF1-expression by the germ cells of the involuted monkey tubules indicated their stem cell identity (Fig. 7). "
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    ABSTRACT: Mammalian spermatogenesis is maintained by spermatogonial stem cells (SSCs). However, since evidentiary assays and unequivocal markers are still missing in non-human primates (NHPs) and man, the identity of primate SSCs is unknown. In contrast, in mice, germ cell transplantation studies have functionally demonstrated the presence of SSCs. LIN28 is an RNA-binding pluripotent stem cell factor, which is also strongly expressed in undifferentiated mouse spermatogonia. By contrast, two recent reports indicated that LIN28 is completely absent from adult human testes. Here, we analyzed LIN28 expression in marmoset monkey (Callithrix jacchus) and human testes during development and adulthood and compared it with that in mice. In the marmoset, LIN28 was strongly expressed in migratory primordial germ cells and gonocytes. Strikingly, we found a rare LIN28-positive subpopulation of spermatogonia also in adult marmoset testis. This was corroborated by western blotting and quantitative RT-PCR. Importantly, in contrast to previous publications, we found LIN28-positive spermatogonia also in normal adult human and additional adult NHP testes. Some seasonal breeders exhibit a degenerated (involuted) germinal epithelium consisting only of Sertoli cells and SSCs during their non-breeding season. The latter re-initiate spermatogenesis prior to the next breeding-season. Fully involuted testes from a seasonal hamster and NHP (Lemur catta) exhibited numerous LIN28-positive spermatogonia, indicating an SSC identity of the labeled cells. We conclude that LIN28 is differentially expressed in mouse and NHP spermatogonia and might be a marker for a rare SSC population in NHPs and man. Further characterization of the LIN28-positive population is required.
    Molecular Human Reproduction 06/2012; 18(10):477-88. DOI:10.1093/molehr/gas025 · 3.48 Impact Factor
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    • "Neonatal testicular stem cells originating from the mouse (Kanatsu-Shinohara et al., 2005; Kanatsu-Shinohara et al., 2007) or rat (Munsie et al., 1997; Ravindranath et al., 1997; Orwig et al., 2002; van Bragt et al., 2008) are thought to be the main occupants of this tissue within the first few days of life. In the first 3-7days postpartum, seminiferous tubular type A spermatogonia have been *Corresponding author. "
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    ABSTRACT: Neonatal testicular germline stem cell suspension prepared from twenty 3-5 day old albino rats were incubated in normal saline or in NC-01in triplicate groups. A control group of saline alone (without cell suspension) was also prepared. The cell-containing groups and control were incubated for 21 days at room temperature, stained with 50% Mezo (organic) and visually studied daily with a view to histological characterizing the changes in cellular aggregation, morphology and coloration during incubation. Images of dense oval cells and cellular developmental transformation into mixed populations of these testicular cells showed clearly identifiable patterns of clump formation. Saline alone (control) did not show the presence of any cells during the period of incubation. In vitro expansion of neonatal germline stem cells within 21 days of incubation was associated with multiple divisions into numerous structurally similar cells and transformation into clusters of multi-colored component rod-like cells. A many-fold increase in the number of dense oval cells was observed in the NC-01 culture medium than in the normal saline. Using these morphological criteria and functional characteristics, we suggest a many-fold increased presence of rat neonatal spermatogonial stem cells capable of cellular division in NC-01 culture medium than in normal saline.
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