Article
Lab Invest 2003, 83:449–456
Impaired Gap Junction Connexin43 in Sertoli Cells of Patients with Secretory Azoospermia: A Marker of Undifferentiated Sertoli Cells
The two first authors contributed equally to this work. This research was supported in part by the Ligue Nationale contre le Cancer and by Association pour la Recherche contre le Cancer (Grant 98-80). ND was supported by grants from the Agence de l'Environnement et de la Maîtrise de l'Energie and BM was supported by grants from the Fondation Fertilité Stérilité and Organon.
Norah Defamie1, Isabelle Berthaut3, Baharia Mograbi1, Daniel Chevallier1, Jean-Pierre Dadoune3, Patrick Fénichel1, Dominique Segretain2 and Georges Pointis1
- 1INSERM EMI 00-09, IFR 50, Faculté de Médecine, Nice Cedex, France
- 2Université Paris V, Paris, France
- 3Groupe d'Etude de la Formation et de la Maturation du gamète mâle, Laboratoire de Cytologie et d'Histologie, UFR Biomédicale, Paris, France
Correspondence: Dr. G. Pointis, INSERM EMI 00-09, IFR 50, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 2, France. E-mail: pointis@unice.fr
Received 28 October 2002.
Abstract
Gap junctions are intercellular channels formed of connexins (Cx) at appositional plasma membranes between adjacent cells that have been involved in the control of cell proliferation and differentiation. Altered Cx expression is implicated consistently in several human diseases and in tumorigenesis. Although Cx43 plays a critical role in Sertoli cell control of spermatogenesis, there is no evidence of its altered expression in human testicular pathologies. We show here that Cx43 mRNA expression was significantly reduced in testes of infertile patients with secretory azoospermia (p < 0.05) compared with testes displaying normal spermatogenesis (excretory azoospermic patients). In Sertoli cell-only syndrome, in situ hybridization and immunohistochemistry analyses indicated that Cx43 mRNA and protein were undetectable in Sertoli cells but were still present in the interstitial compartment. In a rat model of Sertoli cell-only syndrome, the lack of Cx43 in Sertoli cells was associated with an impairment of gap junction intercellular communication between adjacent Sertoli cells. These results reveal that Cx43 mRNA and protein expression are markedly impaired in Sertoli cells of infertile patients. This defect could be a new functional marker of undifferentiated Sertoli cells and could be related to the increased risk of testicular cancer recently described in the population of infertile men.
