Opposite regulation of connexin33 and connexin43 by LPS and IL-1alpha in spermatogenesis

Am J Physiol Cell Physiol. 2006 Mar;290(3):C733-40. doi: 10.1152/ajpcell.00106.2005. Epub 2005 Oct 19.


The gap junction proteins, connexins (Cxs), are present in the testis, and among them, Cx43 play an essential role in spermatogenesis. In the present study, we investigated the testicular expression and regulation of another Cx, Cx33, previously described as a negative regulator of gap junction communication. Cx33 mRNA was present in testis and undetectable in heart, liver, ovary, and uterus. In the mature testis, Cx33 was specifically immunolocalized in the basal compartment of the seminiferous tubules, whereas Cx43 was present in both seminiferous tubule and interstitial compartments. During stages IX and X of spermatogenesis, characterized by Sertoli cell phagocytosis of residual bodies, Cx43 was poorly expressed within seminiferous tubules, while Cx33 signal was strong. To evaluate the role of phagocytosis in the control of Cx33 and Cx43 expression, the effect of LPS was analyzed in the Sertoli cell line 42GPA9. We show herein that phagocytosis activation by LPS concomitantly stimulated Cx33 and inhibited Cx43 mRNA levels. These effects appear to have been mediated through IL-1alpha, because the exposure of Sertoli cells to the IL-1 receptor antagonist partly reversed these effects. IL-1alpha enhanced and reduced, respectively, the levels of Cx33 and Cx43 mRNA in a time- and dose-dependent manner. These data reveal that Cx33 and Cx43 genes are controlled differently within the testis and suggest that these two Cxs may exert opposite and complementary effects on spermatogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Line
  • Connexin 43 / genetics
  • Connexin 43 / metabolism*
  • Connexins / genetics
  • Connexins / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Developmental
  • Interleukin-1 / metabolism
  • Interleukin-1 / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Male
  • Organ Specificity
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Spermatogenesis / drug effects*
  • Testis / cytology
  • Testis / drug effects
  • Testis / metabolism


  • Connexin 43
  • Connexins
  • Interleukin-1
  • Lipopolysaccharides
  • RNA, Messenger
  • Gja6 protein, rat
  • Extracellular Signal-Regulated MAP Kinases