Source, catabolism and role of the tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro within the testis

Copyright © 2000 by Company of BiologistsThe tetrapeptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (AcSDKP) is a natural regulator of hematopoietic stem cell proliferation. The present study was aimed at investigating the presence and the role of AcSDKP in rat testis. Specific immunoreactivity was always observed in the interstitial tissue at all stages of testicular development and in elongated spermatids at 45 days of age and in adults. In accordance with the interstitial labeling, high AcSDKP levels were detected in Leydig cell and testicular macrophage culture media and cell extracts, as well as in the testicular interstitial fluid (TIF). Much lower concentrations were found in peritubular cells and Sertoli cells cultures, whereas very low concentrations were present in cultured spermatocytes and spermatids. In contrast to the slight degradation rate of AcSDKP observed in the spermatocyte and spermatid culture media, no catabolism of the peptide was seen in testicular somatic cell culture medium. Furthermore, the degradation rate of AcSDKP was much lower in TIF than in peripheral blood plasma. Despite the very strong evidence indicating that Leydig cells and testicular macrophages produce AcSDKP, the selective destruction of these cells did not result in any change in AcSDKP levels in TIF or in plasma. This suggests a compensatory mechanism ensuring constant levels of the peptide in TIF when interstitial cells are absent. Finally, in vitro, in the presence of AcSDKP, significantly more [(3)H]thymidine incorporation was found in A spermatogonia. In conclusion, this study establishes the presence of very high concentrations of AcSDKP in rat testis and demonstrates its Leydig cell and testicular macrophage origin. The presence of AcSDKP in the TIF and its stimulatory effect on thymidine incorporation in spermatogonia very strongly suggest its implication in the paracrine control of spermatogenesis.Jean-Philippe Stéphan, Nathalie Melaine, Eric Ézan, Harri Hakovirta, Simon Maddocks, Jorma Toppari, Danielle-Hélène Garnier, Joanna Wdzieczak-Bakala and Bernard Jégo

Etude moléculaire de la défense antivirale et antixénobiotique testiculaire

RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Identification and characterization of novel anti-infectious peptides from the male genital tract.

International audienceAntimicrobial resistance has become aggravated over the last 20 years. During this period pharmaceutical industries have focused on making incremental improvements on long-established antibiotics and, to an extent, sidelined the search for new drugs to overcome pharmaco-resistance strategies currently employed by pathogens. As a consequence bacterial infections are, to date, the most morbid and resistant among infectious diseases. This is, in particular, true for: diarrheic or respiratory infections, meningitis, sexually transmitted diseases and nosocomial infections. The time has come to discover innovative molecules for anti-infection therapies. Among new molecules with potential interest are antimicrobial peptides, an important component of the natural defenses of most living organisms. These are welcomed as serious candidates considering: their rapid microbicidal action, their broad spectrum of activity (bacteria, fungi, parasites, enveloped virus) and their original mechanism of action; the latter being difficult to evade by the resistance strategies employed by bacteria. Over the past decade, more than 700 microbicidal peptides have been inferred from various species including vertebrates. In the latter it is known that organs of the male genital tract express a potent and sophisticated anti-infectious defense system based partly on antimicrobial peptides. It follows that major reproductive organs such as the testis and epididymis are an ideal source for novel, highly specific microbicidal peptides. Using state-of-the-art proteomics and innovative syntactical biocomputing approaches, we identified numerous peptides with antimicrobial properties. This establishes the male genital tract as a veritable gold-mine for new anti-infectious agents to be exploited for future medicine

Identification and characterization of novel anti-infectious peptides from the male genital tract.

International audienceAntimicrobial resistance has become aggravated over the last 20 years. During this period pharmaceutical industries have focused on making incremental improvements on long-established antibiotics and, to an extent, sidelined the search for new drugs to overcome pharmaco-resistance strategies currently employed by pathogens. As a consequence bacterial infections are, to date, the most morbid and resistant among infectious diseases. This is, in particular, true for: diarrheic or respiratory infections, meningitis, sexually transmitted diseases and nosocomial infections. The time has come to discover innovative molecules for anti-infection therapies. Among new molecules with potential interest are antimicrobial peptides, an important component of the natural defenses of most living organisms. These are welcomed as serious candidates considering: their rapid microbicidal action, their broad spectrum of activity (bacteria, fungi, parasites, enveloped virus) and their original mechanism of action; the latter being difficult to evade by the resistance strategies employed by bacteria. Over the past decade, more than 700 microbicidal peptides have been inferred from various species including vertebrates. In the latter it is known that organs of the male genital tract express a potent and sophisticated anti-infectious defense system based partly on antimicrobial peptides. It follows that major reproductive organs such as the testis and epididymis are an ideal source for novel, highly specific microbicidal peptides. Using state-of-the-art proteomics and innovative syntactical biocomputing approaches, we identified numerous peptides with antimicrobial properties. This establishes the male genital tract as a veritable gold-mine for new anti-infectious agents to be exploited for future medicine

Proteomics and integrative genomics for unraveling the mysteries of spermatogenesis: the strategies of a team

International audienceThe strikingly complex structural organization of the mammalian testis in vivo creates particular difficulties for studies of its organization, function and regulation. These difficulties are particularly pronounced for investigations of the molecular communication networks within the seminiferous tubules that govern spermatogenesis. The use of classical molecular and cell biology approaches to unravel this complexity has proved problematic, due to difficulties in maintaining differentiated germ cells in vitro, in particular. The lack of a suitable testing ground has led to a greater reliance on high-quality proteomic and genomic analyses as a prelude to the in vitro antx1d in vivo testing of hypotheses. In this study, we highlight the options currently available for research, as used in our laboratory, in which proteomic and integrative genomic strategies are applied to the study of spermatogenesis in mammals. We will comment on results providing insight into the molecular mechanisms underlying normal and pathological spermatogenesis and new perspectives for the treatment of male infertility in humans. Finally, we will discuss the relevance of our strategies and the unexpected potential and perspectives they offer to teams involved in the study of male reproduction, within the framework of the Human Proteome Project. SIGNIFICANCE: Integrative genomics is becoming a powerful strategy for discovering the biological significance hidden in proteomic datasets. This work introduces some of the integrative genomic concepts and works used by our team to gain new insight into mammalian spermatogenesis, a remarkably sophisticated process. We demonstrate the relevance of these integrative approaches to understand the cellular cross talks established between the somatic Sertoli cells and the germ cell lineage, within the seminiferous epithelium. Our work also contributes to new knowledge on the pathophysiology of testicular function, with promising clinical applications. This article is part of a Special Issue entitled: 20years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez

Quelle stratégie participative pour la gestion locale de l’eau avec les citoyens ? Retours d’expérience et questions à se poser

Dans le cadre du projet « Quelle stratégie participative pour la gestion locale de l’eau avec les citoyens », cinq terrains ont été accompagnés par IRSTEA dans la construction et la mise en œuvre d’une démarche participative avec les citoyens : la Sévenne, les Usses, l’Huveaune, l’Arc et la Drôme. Ces terrains sont représentatifs de différentes zones du bassin Rhône Méditerranée Corse et de différents enjeux auxquels cherchent à répondre les gestionnaires de l’eau: restauration hydromorphologique, partage de l’eau entre différentes usages, inondations et gestion intégrée. Ce document a été construit autour des questions que se sont posées les gestionnaires de l’eau de ces cinq terrains avant, pendant et après leurs démarches participatives. Par exemple : Pourquoi se lancer et dans quel(s) cas ne pas se lancer dans une démarche participative ? La démarche visée respecte-t-elle les obligations règlementaires en termes de participation ? Comment communiquer pour mobiliser les citoyens ? Comment organiser les groupes de participants ? Pourquoi et comment concevoir une charte de la participation ? Comment savoir ce que les participants ont pensé ou appris du processus participatif ? Quels sont les effets des démarches participatives sur les élus ? Nous avons fait l’hypothèse que d’autres gestionnaires se poseraient les mêmes questions et qu’ils seraient donc intéressés par les choix qu’ont fait les cinq terrains pour y répondre et les enseignements qu’ils en ont tiré

Quelle stratégie participative pour la gestion locale de l’eau avec les citoyens ? Retours d’expérience et questions à se poser

Dans le cadre du projet « Quelle stratégie participative pour la gestion locale de l’eau avec les citoyens », cinq terrains ont été accompagnés par IRSTEA dans la construction et la mise en œuvre d’une démarche participative avec les citoyens : la Sévenne, les Usses, l’Huveaune, l’Arc et la Drôme. Ces terrains sont représentatifs de différentes zones du bassin Rhône Méditerranée Corse et de différents enjeux auxquels cherchent à répondre les gestionnaires de l’eau: restauration hydromorphologique, partage de l’eau entre différentes usages, inondations et gestion intégrée. Ce document a été construit autour des questions que se sont posées les gestionnaires de l’eau de ces cinq terrains avant, pendant et après leurs démarches participatives. Par exemple : Pourquoi se lancer et dans quel(s) cas ne pas se lancer dans une démarche participative ? La démarche visée respecte-t-elle les obligations règlementaires en termes de participation ? Comment communiquer pour mobiliser les citoyens ? Comment organiser les groupes de participants ? Pourquoi et comment concevoir une charte de la participation ? Comment savoir ce que les participants ont pensé ou appris du processus participatif ? Quels sont les effets des démarches participatives sur les élus ? Nous avons fait l’hypothèse que d’autres gestionnaires se poseraient les mêmes questions et qu’ils seraient donc intéressés par les choix qu’ont fait les cinq terrains pour y répondre et les enseignements qu’ils en ont tiré