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Connexines testiculaires: marqueurs physiopathologiques et cibles potentielles aux toxiques environnementaux

Testicular connexins: pathophysiological markers and potential targets for environmental toxins

Résumé

Les jonctions communicantes et leurs protéines constitutives, les connexines (Cxs), sont des constituants nécessaires à la cohésion tissulaire et reconnus comme suppresseurs de tumeurs. Le but de la présente revue est de faire le point sur l’organisation et le rôle des Cxs au sein du testicule et d’analyser leur expression en physiopathologie testiculaire. Organisées en structures hexamèriques formant un canal reliant directement les cytoplasmes des cellules adjacentes, les Cxs sont impliquées dans de nombreux processus physiologiques tels que la prolifération et la différenciation cellulaires. Le maintien d’une balance entre prolifération, différenciation et apoptose est un équilibre primordial évitant une prolifération cellulaire anarchique, risque de cancer. La spermatogenèse est un modèle sophistiqué de prolifération et de différenciation des cellules germinales dans lequel les Cxs jouent un rôle essentiel. Il est acquis qu’une altération de l’expression membranaire des Cxs est l’un des signes avant-coureurs de la cinétique tumorale germinale, et il a été suggéré que les toxiques environnementaux qui, dans leur grande majorité, affectent l’expression de ces protéines, puissent être impliqués dans le développement de cette pathologie. La recherche de molécules capables de freiner les effets délétères de toxiques carcinogènes sur les Cxs semble être à l’heure actuelle une voie intéressante ouvrant de nouvelles perspectives en santé humaine.

Abstract

Gap junctions and their constitutive proteins, connexins, are essential in cell homeostasis and are considered as tumour suppressors. The purpose of the present review is to discuss the role of connexins in the testis and their expression in testis physiopathology. Organized in an hexameric arrangement forming a channel that connects cytoplasms of adjacent cells, connexins are implicated in numerous physiological processes such as cell proliferation and differentiation. The balance between cell proliferation/differentiation/apoptosis is prerequisite for limiting anarchic cell proliferation, a major risk of cancer development. Spermatogenesis is a sophisticated model of germ cell proliferation and differentiation in which connexins play an essential role. It is well recognized that alteration of membranous expression of connexins is an early event of germ cell tumoral kinetics and it has been suggested that environmental toxicants such as non-genomic carcinogens, which in most cases impair connexin expression, could be associated with testis tumoral development. The identification of agents capable of regulating the deleterious effects of carcinogens on connexin expression could be today of interest for opening new therapeutic perspectives.

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Correspondence to D. Segretain.

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Mots clés

  • Communication jonctionnelle intercellulaire par gap
  • Connexines
  • Pathologies testiculaires
  • Séminome
  • Toxiques environnementaux

Keywords

  • Intercellular gap junction communication
  • Gap junction
  • Connexin
  • Testis pathologies
  • Seminoma
  • Environmental toxicants