title: Impaired gap junction connexin43 in Sertoli cells of patients with secretory azoospermia: a marker of undifferentiated Sertoli cells.
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.
authors.affiliation: INSERM EMI 00-09, IFR 50, Faculté de Médecine, Nice Cedex, France.
authors.forename: Norah
authors.initials: N
authors.lastname: Defamie
authors.forename: Isabelle
authors.initials: I
authors.lastname: Berthaut
authors.forename: Baharia
authors.initials: B
authors.lastname: Mograbi
authors.forename: Daniel
authors.initials: D
authors.lastname: Chevallier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Dadoune
authors.forename: Patrick
authors.initials: P
authors.lastname: Fénichel
authors.forename: Dominique
authors.initials: D
authors.lastname: Segretain
authors.forename: Georges
authors.initials: G
authors.lastname: Pointis
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009845:Oligospermia / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000378:metabolism*; D013194:Staining and Labeling
chemical_list: D015415:Biomarkers; D018031:Connexin 43; D012333:RNA, Messenger