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

Abstract

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.

Three‐dimensional analysis of connexin43 gap junction in the ex vivo rat seminiferous tubules: Short‐term effects of hormonal effectors

“…It is noteworthy that the reduced Cx43 expression and coupling during stages IX-X occurs when high levels of IL-1a are released by seminiferous tubules fragments isolated at these stages (Syed et al, 1995) and that this cytokine markedly inhibits Sertoli cell Cx43 gene expression (Fiorini et al, 2006). From these findings, one can speculate that the stage-dependent Cx43 expression results from stage-dependent hormonal control and that the model developed here could be useful for analyzing the in vivo situation.…”

Regulation of cell junction dynamics by cytokines in the testis—A molecular and biochemical perspective

“…During phagocytosis of residual bodies, Cx43 is weakly expressed within the seminiferous epithelium, in contrast, Cx33 displays an enhanced expression. Such differential expression pattern is under the precise control of IL-1α and ERK activation since the exposure of Sertoli cells to IL-1 receptor antagonist was shown to reverse this expression pattern [40].…”

“…Connexin33 (Cx33) and Cx43 display stage-specific expression in the seminiferous epithelium coinciding with the event of residual body phagocytosis by Sertoli cells [40]. During phagocytosis of residual bodies, Cx43 is weakly expressed within the seminiferous epithelium, in contrast, Cx33 displays an enhanced expression.…”

Differential effects of c-Src and c-Yes on the endocytic vesicle-mediated trafficking events at the Sertoli cell blood-testis barrier: an in vitro study

“…Second, we used (26)] served as a negative control. Sertoli cells are known phagocytic cells (10,15,31), serving as scavengers to lyse unwanted or defective germ cells. Thus, when Sertoli cells were exposed to FluoSpheres fluorescent microspheres (an analog representation of apoptotic germ cells) at 35°C, phagocytosis took place, and this process was enhanced and blocked by LPS and BLT-1, respectively (Fig.…”