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TGF-ß3 Regulates the Blood-Testis Barrier Dynamics via the p38 Mitogen Activated Protein (MAP) Kinase Pathway: An in Vivo Study

Population Council, New York, New York 10021

Address all correspondence and requests for reprints to: Dr. C. Yan Cheng, The Population Council, 1230 York Avenue, New York, New York 10021. E-mail: Y-Cheng{at}popcbr.rockefeller.edu

Abstract

Recent studies using Sertoli cells cultured in vitro to permit tight junction (TJ) assembly have shown that TJ dynamics are regulated, at least in part, by TGF-ß3 via the p38 mitogen activated protein (MAP) kinase pathway. This in turn regulates the production of occludin, a TJ-integral membrane protein, by Sertoli cells. Yet it is not known if this pathways is used by Sertoli cells to regulate the blood-testis barrier (BTB) function in vivo. Using an in vivo model for studying BTB dynamics, we report herein the CdCl₂-induced BTB damage in rats was associated with a significant reduction in testicular occludin along with a loss of immunoreactive occludin in the seminiferous epithelium at the site of the BTB. Also, this CdCl₂-induced occludin loss from the BTB coincided with a surge in testicular TGF-ß3, as well as p-p38 MAP kinase (the phosphorylated/activated form of p38), but not p38 MAP kinase and neither extracellular signal-regulated kinase nor its phosphorylated form (ERK/p-ERK), consistent with results of in vitro studies. More important, intratesticular administration of SB202190, a specific p38 MAP kinase inhibitor, could block the CdCl₂-induced occludin loss from the BTB. These results illustrate that BTB dynamics in vivo are regulated by the TGF-ß3/p38 MAP kinase pathway, which in turn determines the level of occludin at the site of Sertoli cells TJs.

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