Discrete cell- and stage-specific localisation of fibroblast growth factors and receptor expression during testis development

Cancilla, Belinda; Davies, Ann D. M.; Ford-Perriss, Miriam; Risbridger, Gail P.

doi:10.1677/joe.0.1640149

Cited by 47 publications

(33 citation statements)

References 51 publications

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“…A study of murine primordial germ cells (PGC) detected Fgfr1-IIIc and Fgfr2-IIIb but not Fgfr3 (Takeuchi et al, 2005). Studies in the rat detected Fgfr3-IIIc mRNA throughout the testis development (Cancilla & Risbridger, 1998;Cancilla et al, 2000), while a study in mice reported the presence of mRNA for Fgfr3-IIIb and -IIIc in immuno-purified somatic but not germ cells of fetal XY gonads (Bowles et al, 2010). The Fgfr3 protein product was reported in the cytoplasm of rat fetal germ cells as well as somatic cells, but after puberty the expression was restricted to the cytoplasm of spermatocytes, in a stage dependent manner (Cancilla & Risbridger, 1998; protein level in fetal germ cells after their maturation from gonocytes into pre-spermatogonia.…”

Section: Discussionmentioning

confidence: 99%

Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

Ewen

Olesen²,

Winge³

et al. 2013

Int. J. Dev. Biol.

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Observations in patients with an activating mutation of fibroblast growth factor receptor 3 (FGFR3) suggest a role for FGFR3 signalling in promoting proliferation or survival of germ cells. In this study, we aimed to identify the FGFR3 subtype and the ontogeny of expression during human testis development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3 expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis development, expression of FGFR3 did not directly correlate with proliferation markers. In preinvasive CIS cells and in TGCTs, including classical seminoma and embryonal carcinoma, FGFR3IIIc was detected only in a small number of cells, with a heterogeneous expression pattern. FGFR3 is an excellent marker for human pre-/spermatogonia throughout development. Signalling through this receptor is likely associated with spermatogonial survival rather than proliferation. FGFR3 is not expressed in gonocytes and may not be essential to the aetiology of TGCTs stemming from CIS.

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Section: Discussionmentioning

confidence: 99%

Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

Ewen

Olesen²,

Winge³

et al. 2013

Int. J. Dev. Biol.

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“…FGF2 immunostaining is restricted to PCs and Leydig cells in the rat fetal testis (Gonzales et al 1990). FGF2 is also produced in the rat postnatal testis where it exerts mitogenic and regulatory functions on somatic and/or germinal cells (Mullaney & Skinner 1992, Han et al 1993, Le Magueresse-Battistoni et al 1994, 1996, Van DisselEmiliani et al 1996, Cancilla & Risbridger 1998, Cancilla et al 2000.…”

Section: Discussionmentioning

confidence: 99%

“…FGF2 was first isolated and characterized from bovine testes (Ueno et al 1987), and its presence was next confirmed in the testes of different species, including humans, cows, mice and rats. Evidence then accumulated showing that FGF2 exerted mitogenic and non-mitogenic functions in the rat testis, where several FGFRs have been localized (Mullaney & Skinner 1992, Han et al 1993, Le Magueresse-Battistoni et al 1994, 1996, Van DisselEmiliani et al 1996, Cancilla & Risbridger 1998, Cancilla et al 2000. The importance of FGF9 in testis functions was shown more recently by the finding that most fgf9 / XY reproductive systems appeared grossly female at birth.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor (FGF) 2 and FGF9 mediate mesenchymal–epithelial interactions of peritubular and Sertoli cells in the rat testis

Ramy¹,

Verot²,

Mazaud³

et al. 2005

Journal of Endocrinology

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The role of fibroblast growth factor (FGF) 2 and FGF9 as mediators of cell-cell interactions between Sertoli cells (SCs) and peritubular cells (PCs) was investigated. Using RT-PCR, we demonstrated that SCs and PCs recovered from 20-day-old rats expressed several of the seven FGF receptors (FGFRs), and more specifically the FGFR1 IIIc. FGF2 and FGF9 did not elicit any morphological changes in primary cultures of SCs, nor did they alter the number of SCs in culture. By contrast, changes in shape were observed in FGF2-and FGF9-treated PCs. In addition, FGF2 but not FGF9 enhanced significantly and dosedependently the number of PCs in culture, indicating that FGF2 was a survival factor for these cells. It was also mitogenic because it enhanced the [ 3 H]thymidine labeling index in PCs. We next examined the effects of FGF2 and FGF9 in a coculture system using 20-day-old rat SCs and PCs, and in an organotypic culture system using XY rat embryonic gonads. In both models, FGF2 and FGF9 were found to promote cellular interactions as evidenced by the extent of cellular reorganization in the coculture system, and cord morphogenesis and growth in the organotypic culture system. A key feature in SC-PC interactions is the synthesis and remodeling of the basement membrane which is co-elaborated by the two cell types. Since basement membrane homeostasis depends upon the coordinated activity of proteinases and inhibitors, the proteinases and inhibitors produced by PCs and SCs degrading or opposing degradation of the major components of the basement membrane were further studied. Specifically, we monitored the metalloproteinases (MMP)-2 and -9 and the tissue inhibitors -1, -2 and -3, the plasminogen activators (PAs) and the PA inhibitor-1, using zymography for the proteinases and Western blots for the cognate inhibitors. Cocultures received FGF or an analog of cAMP in order to prevent cellular reorganization. We found that FGF2 was unique in inducing MMP-9 in coculture. Also, the enhanced levels of the PA inhibitor-1 and the 30 kDa band glycosylated form of tissue inhibitor-3 correlated with the enhanced SC-PC reorganization. It was concluded that FGF2 and FGF9 are morphogens for the formation of testicular cords.

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“…Receptors for most of these growth factors are present on Sertoli cells [53,54,55,56,57] and several of them, i.e., FGF-2, IGF-I, IGF-II, TGF-α, EGF, activin A, have been found to stimulate the growth of these cells, although contradictory reports have also appeared [13,58,59,60,61,62,63]. A number of these growth factors also appear to influence other Sertoli cell functions, such as the production of lactate and transferrin (for a review, see [64]).…”

Section: Paracrine Regulationmentioning

confidence: 99%

The Sertoli Cell – A Hormonal Target and ‘Super’ Nurse for Germ Cells That Determines Testicular Size

Petersen

Söder²

2006

Horm Res Paediatr

162

148

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The somatic Sertoli cell plays an essential role in embryonic determination of male somatic sex and in spermatogenesis during adult life. One individual Sertoli cell supplies a clone of developing germ cells with nutrients and growth factors and it is well established that the number of Sertoli cells present is closely correlated to both testicular size and sperm output. Sertoli cells continue to proliferate and differentiate until the beginning of puberty, when they cease dividing and start nursing the germ cells. At this point in time, the future capacity of the testis for sperm production has thus been determined. Prior to puberty the Sertoli cells are immature and differ considerably with respect to morphology and biochemical activity from the mature cell. The several investigations that have focused on hormonal and paracrine regulation of the functions of the mature cell are reviewed here, but the mechanisms underlying the maturation and general maintenance of well-functioning Sertoli cells remain obscure. An alarming decline in male reproductive health has been observed in several Western countries during recent decades. Disturbance of Sertoli cell differentiation is thought to be involved in the pathogenesis of both a poor sperm count and testicular cancer. It is speculated that environmental agents that disrupt the estrogenic/androgenic balance in the testis may play a role in this connection.

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Discrete cell- and stage-specific localisation of fibroblast growth factors and receptor expression during testis development

Cited by 47 publications

References 51 publications

Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

Fibroblast growth factor (FGF) 2 and FGF9 mediate mesenchymal–epithelial interactions of peritubular and Sertoli cells in the rat testis

The Sertoli Cell – A Hormonal Target and ‘Super’ Nurse for Germ Cells That Determines Testicular Size

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