Stem cell factor and c-kit in the mammalian testis: lessons originating from Mother Nature's gene knockouts

Loveland, Kate L; Schlatt, Stefan

doi:10.1677/joe.0.1530337

Cited by 155 publications

(87 citation statements)

References 59 publications

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“…It is well-known that spermatogenesis is regulated by the interaction between proliferation and cell death (De Krester & Kerr, 1994;Blanco-Rodr ıguez & Mart ınez-Garc ıa, 1996;Loveland & Schlatt, 1997). This interaction occurs in normal physiological conditions and pathological conditions both of which may result in the elimination of germ cells.…”

Section: Introductionmentioning

confidence: 99%

Testicular histomorphometry and the proliferative and apoptotic activities of the seminiferous epithelium in Syrian hamster (Mesocricetus auratus) during regression owing to short photoperiod

et al. 2015

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SUMMARYDuring the non-breeding season some animals exhibit testicular atrophy, decreased testicular weight and reduced seminiferous tubule diameter accompanied by depletion of the seminiferous epithelium. Some cellular factors involved in this depletion are changes in germ cell proliferation and apoptosis. In the Syrian hamster this depletion has been studied histologically and in terms of the involvement of proliferation and apoptosis in the seminiferous epithelium of fully regressed testes. The objectives of this study included the histomorphometrical characterization of the testis and the determination of the proliferative and apoptotic activity of germ cells in the seminiferous epithelium during testicular regression owing to short photoperiod. The study was performed using conventional light microscopy (hematoxylin and eosin), proliferating cell nuclear antigen and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end labelling staining, image analysis software, and transmission electron microscopy in three established regression groups: mild regression (MR), strong regression (SR), and total regression (TR). Morphometrically a gradual decrease in total tubular area and in the testicular, tubular, and epithelial volumes was observed during testicular regression. Interstitial and luminal volumes decreased from the MR group onwards. The tubular length decreased from MR to SR. As regards spermatogonial proliferation, only an initial decrease in proliferative activity was observed, whereas apoptotic germ cell activity increased throughout regression. The number of germ cells studied decreased throughout the process of testicular regression. In conclusion, testicular regression in Syrian hamster comprises two histomorphometrical phases, the first involving a decrease in seminiferous tubular diameter and volume and the second involving shortening of the seminiferous tubule and a decrease in interstitial volume. At the cellular level, there is an initial decrease in proliferation and increase in apoptosis involving all germ cells. At the end of regression, the proliferative and apoptotic activities of the spermatogonia recover the values observed prior to regression in preparation for recrudescence.

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Section: Introductionmentioning

confidence: 99%

Testicular histomorphometry and the proliferative and apoptotic activities of the seminiferous epithelium in Syrian hamster (Mesocricetus auratus) during regression owing to short photoperiod

et al. 2015

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“…In mutant mice, abnormalities of the SCF/c-kit gene expression, such as gene deletions, point mutations, alternative splicing defects, lead to different changes in spermatogenesis (e.g. decreased primordial germ cell migration, decreased in spermatogonial proliferation; for reviews, see Morrison & Takahashi 1993, Loveland & Schlatt 1997.…”

Section: Introductionmentioning

confidence: 99%

The c-kit receptor protein in the testis of green frog Rana esculenta: seasonal changes in relationship to testosterone titres and spermatogonial proliferation

Raucci¹,

Fiore²

2007

Reproduction

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The green frog Rana esculenta is a seasonal breeder. The cyclic changes between almost arrested and highly activated spermatogenesis offer an ideal model to study basic mechanisms of spermatogenesis. In this study, we demonstrated, to our knowledge for the first time, c-kit receptor positive cells in the testis of this amphibian. The presence of c-kit receptor protein was confirmed by western blotting (Wb) analyses carried out in the testis during all the three main phases of the sexual cycle. The antibody recognized a band of about 150 kDa that was correlated with the positive staining in the germinal epithelium. The immunolabelling for c-kit receptor, evaluated by immunohistochemistry (IHC), was localized in I and II spermatogonia (SPG), in I and II spermatocytes, in both elongating spermatids and spermatozoa and in the Leydig cells. Furthermore, c-kit expression showed a seasonal pattern connected with both testicular and plasma profiles of testosterone during the reproductive cycle. The highest expression of c-kit receptor occurred during the reproductive period, when the testis exhibited the maximum concentration of testosterone. In this period, the mitotic activity of germ cell, assessed by both Wb and IHC analyses for proliferating cell nuclear antigen (PCNA), was intensive. Indeed, during the post-reproductive period, testosterone titres were the lowest and the expression of both PCNA and c-kit receptor protein in the testis, although present, is minor when compared with the reproductive phase. This evidence suggests that cell division can continue sufficiently to accumulate SPG for the next spring, when new germinal cells undergo multiplication. Finally, during the pre-reproductive period, testosterone levels begin to increase and mitotic activity of germinal epithelium is comparably enhanced. These events seem to precede the period of maximum stimulated spermatogonial proliferation, i.e. the reproductive period. These results suggest that the c-kit receptor may play a role in germ cell proliferation and provide a basis for future detailed investigation of regulatory factors of the proliferation of SPG.

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“…Among the many regulatory factors that tightly control spermatogenesis, the interaction of Kit (known as c-Kit) receptor protein with its ligand, Kitl (also known as Kit ligand and stem cell factor, and referred to here as SCF), plays essential roles, including its specific influence on spermatogonial differentiation and survival at the onset of spermatogenesis (for review see Loveland & Schlatt 1997, de Rooij & Grootegoed 1998, Yan et al 2000. The c-Kit gene encodes a transmembrane tyrosine kinase receptor for the SCF protein.…”

Section: Introductionmentioning

confidence: 99%

“…The c-Kit gene encodes a transmembrane tyrosine kinase receptor for the SCF protein. SCF is produced as an integral membrane protein that may be cleaved to release a soluble, extracellular ligand (Loveland & Schlatt 1997). Expression and functional studies indicate that c-Kit is developmentally regulated in male germ cells during both fetal and postnatal development (for review see Mauduit et al 1999) and localized in Leydig cells in both 6-day postnatal and adult mice (Manova et al 1990, Rothschild et al 2003 with the capacity to influence steroidogenesis.…”

Section: Introductionmentioning

confidence: 99%

Expression of c-Kit receptor mRNA and protein in the developing, adult and irradiated rodent testis

Prabhu¹,

Meistrich²,

McLaughlin³

et al. 2006

Reproduction

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Germ cell proliferation, migration and survival during all stages of spermatogenesis are affected by stem cell factor signalling through the c-Kit receptor, the expression and function of which are vital for normal male reproductive function. The present study comprehensively describes the c-Kit mRNA and protein cellular expression profiles in germ cells of the postnatal and adult rodent testis, revealing their significant elevation in synthesis at the onset of spermatogenesis. Real-time PCR analysis for both mice and rats matched the cellular mRNA expression profile where examined. Localization studies in normal mouse testes indicated that both c-Kit mRNA and protein are first detectable in differentiating spermatogonia. In addition, all spermatogonia isolated from 8-day-old mice displayed detectable c-Kit mRNA, but 30 -50% of these lacked protein expression. The c-Kit mRNA and protein profile in normal rat testes indicated expression in gonocytes, in addition to differentiating spermatogonia. However, in the irradiated adult rat testes, in which undifferentiated spermatogonia are the only germ cell type, mRNA was also detected in the absence of protein. This persisted at 3 days and 1 and 2 weeks following treatment with gonadotrophin-releasing hormone (GnRH) antagonist to stimulate spermatogenesis recovery. By 4 weeks of GnRH antagonist treatment, accompanying the emergence of differentiating spermatogonia, both mRNA and protein were detected. Based on these observations, we propose that c-Kit mRNA and protein synthesis are regulated separately, possibly by influences linked to testis maturation and circulating hormone levels.

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Stem cell factor and c-kit in the mammalian testis: lessons originating from Mother Nature's gene knockouts

Cited by 155 publications

References 59 publications

Testicular histomorphometry and the proliferative and apoptotic activities of the seminiferous epithelium in Syrian hamster (Mesocricetus auratus) during regression owing to short photoperiod

Testicular histomorphometry and the proliferative and apoptotic activities of the seminiferous epithelium in Syrian hamster (Mesocricetus auratus) during regression owing to short photoperiod

The c-kit receptor protein in the testis of green frog Rana esculenta: seasonal changes in relationship to testosterone titres and spermatogonial proliferation

Expression of c-Kit receptor mRNA and protein in the developing, adult and irradiated rodent testis

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