Characterization of tumour necrosis factor-alpha-related apoptosis-inducing ligand and its receptors in the adult human testis.

Institut National de la Santé et de la Recherche Médicale, INSERM U-407, Communications Cellulaires en Biologie de la Reproduction, Faculté de Médecine Lyon-Sud, BP 12, F-69921 Oullins Cedex, France.
Molecular Human Reproduction (Impact Factor: 3.48). 03/2004; 10(2):123-8.
Source: PubMed

ABSTRACT Tumour necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor-alpha (TNF-alpha) family of cytokines which is known to induce apoptosis upon binding to its death domain-containing receptors, DR4/TRAIL-R1 and DR5/TRAIL-R2. Two additional TRAIL receptors, DcR1/TRAIL-R3 and DcR2/TRAIL-R4, lack functional death domains and act as decoy receptors for TRAIL. In this study, the presence of TRAIL and its receptors was investigated by immunohistochemistry in adult human testes. In addition, TRAIL and its receptors were studied in terms of protein and mRNA using western blot analysis and RT-PCR respectively. TRAIL and its receptors were immunodetected according to the different testicular cell types: TRAIL, DR5/TRAIL-R2 and DcR2/TRAIL-R4 were localized in Leydig cells, DR4/TRAIL-R1 was seen in peritubular and Sertoli cells whereas ligand and all receptors were detected in germ cells. Proteins and mRNA corresponding to TRAIL and its receptors were also identified in adult human testes. In conclusion, TRAIL and its receptors DR4/TRAIL-R1, DR5/TRAIL-R2, DcR1/TRAIL-R3 and DcR2/TRAIL-R4 are expressed in the human testis, and are predominantly localized in different germ cell types.

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    • "Although OPG has been initially identified as a member of the soluble tumor necrosis factor (TNF)-receptor family, inhibiting RANKLmediated osteoclastogenesis, several in vitro studies have shown its ability to also neutralize TRAIL (Emery et al. 1998, Miyashita et al. 2004, Zauli et al. 2009). Among different tissues, it is noteworthy that TRAIL and its receptors are abundantly expressed in human testis (Grataroli et al. 2004). Although TRAIL has been proposed to contribute to the control of the number of spermatogonia (Coureuil et al. 2010), the physiopathological role of TRAIL in testis remains to be fully elucidated. "
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    ABSTRACT: The expression of TRAIL and of its receptors (TRAIL-R1, TRAIL-R2, TRAIL-R3, TRAIL-R4) has been documented in testis, but the presence of soluble TRAIL in seminal fluid, as well as the potential physiopathological role of the TRAIL/TRAIL-R system in spermatozoa, has not been previously investigated. Male donors (n=123) belonging to couples presenting for infertility evaluation were consecutively enrolled in this study. The presence of soluble TRAIL was analyzed in seminal samples by ELISA, while the surface expression of TRAIL receptors was investigated by flow cytometry. High levels of soluble TRAIL were detected in seminal plasma (median: 11621 pg/ml; mean±SD: 13371±8367 pg/ml) and flow cytometric analysis revealed a variable expression of TRAIL receptors in the sperm cellular fraction among different subjects. In addition, the effect of physiologically relevant concentrations of recombinant TRAIL was investigated on survival and motility of spermatozoa. Of interest, the in vitro exposure of capacitated spermatozoa to recombinant TRAIL (10 ng/ml) significantly preserved their overall survival. Therefore, the present study documents for the first time the presence of elevated levels of the anti-inflammatory cytokine TRAIL in seminal fluids. Moreover, the demonstration that recombinant TRAIL promotes spermatozoa survival after capacitation suggests potential therapeutic implications.
    Reproduction 05/2014; DOI:10.1530/REP-14-0144
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    • "Additionally, DR5 receptors were observed in Leydig cells whereas DR4 receptors were expressed in post-meiotic germ cells. In a later study, Grataroli et al. (2004) demonstrated by using immunohistochemistry that TRAIL and its receptors were expressed in different human testicular germ cell types. TRAIL and receptor DR5 as well as decoy receptors were localized in Leydig cells, whereas DR4 receptor was detected in human peritubular and Sertoli cells. "
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    ABSTRACT: The spermatozoon is a highly specialized cell, which main function is to transport the male haploid genome in the female genital tract and to deliver it during fertilization of the oocyte. Several reports have shown that the molecular machinery involved in apoptosis in somatic cells is also present in sperm cells during their generation in the testis as well as in the mature, ejaculated mammalian spermatozoa. The aim of the present chapter is to give an overview of recent research on apoptosis in male germ cells and in ejaculated spermatozoa, pointing out its regulation and potential role in important sperm functions. The potential role that oxidative-stress and mitochondrial dysfunction could play as inductors of apoptosis in both fresh and frozen-thawed spermatozoa will be also discussed.
    03/2009: pages 165-209;
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    • "), Erkkila et al. (1997), Lee et al. (1997), Creemers et al. (2002), Sofikitis et al. (2005) TRAIL GC,LC,PC,SC Induction of apoptosis O'Donnell et al. (2001), Schlatt et al. (1997), Gotaroli et al. (2004), Tesarik et al. (2000, 2001), Erkkila et al. (1997), Lee et al. (1997), Creemers et al. (2002), Sofikitis et al. (2005) The effect of each factor on the spermatogenesis process and the producing/expressing cells and the target cells are presented in this table. SC—Sertoli cells; PC—peritubular cells; LC Leydig cells; GC— germ cells; R-SPT—round spermatid; SPC—spermatocytes; P-SPC—pachyten spermatocytes; SPG—spermatogonia; GC—germ cells; SPT—spermatid; E-SPT—elongated spermatid. "
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    ABSTRACT: Spermatogenesis is regulated mainly by endocrine factors and also by testicular paracrine/autocrine growth factors. These factors are produced by Sertoli cells, germ cells, peritubular cells and interstitial cells, mainly Leydig cells and macrophages. The interactions and the ratio between Sertoli and germ cells in the seminiferous tubules ensure successful spermatogenesis. In order to culture spermatogonial stem cells (SSCs) in vitro, researchers tried to overcome some of the obstacles -- such as the low number of stem cells in the testis, absence of specific markers to identify SSCs -- in addition to difficulties in keeping the SSCs alive in culture. Recently, some growth factors important for the proliferation and differentiation of SSCs were identified, such as glial cell line derived neurotrophic factor (GDNF), stem cell factor (SCF) and leukemia inhibitory factor (LIF); also, markers for SSCs at different stages were reported. Therefore, some groups succeeded in culturing SSCs (under limitations), or more differentiated cells and even were able to produce in vitro germ cells from embryonic stem cells. Thus, success in culturing SSCs is dependent on understanding the molecular mechanisms behind self-renewal and differentiation. Culture of SSCs should be a good tool for discovering new therapeutic avenue for some infertile men or for patients undergoing chemotherapy/radiotherapy (pre-puberty or post-puberty).
    Growth Factors 09/2007; 25(4):236-52. DOI:10.1080/08977190701783400 · 3.09 Impact Factor
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