Sertoli cells are important in determining fate of spermatogenic cells by providing nutrition and structural support via cell junctions. In this study we sought to examine the effect of 43°C warming on cell junctions in seminiferous epithelium and the expression of junction-associated molecules in Sertoli cells. Electron microscopy showed the appearance of large vacuoles between Sertoli and germ cells, and adjacent Sertoli cells leading to disruption of corresponding cell junctions 24h after terminating the heat treatment. Using primary Sertoli cells isolated from pubertal monkey testes, we demonstrated that expression of adherens junctions (AJs)-associated molecules, such as N-cadherin and -catenin, and tight junctions (TJs)-associated molecule ZO-1 was significantly reduced in 24–48h after heat treatment. In contrast, intermediate filament vimentin expression was upregulated in 6h-48h.

Androgen receptor (AR) and Wilms' tumor gene (WT1) expression dramatically decreased after heat treatment. Both proteins completely disappeared immediately after terminating heat treatment and began to recover after 6h. Treatment of the monkey Sertoli cells with an androgen receptor antagonist, flutamide, could mimic the heat-induced changes in the expression of junction-associated molecules in Sertoli cells. Furthermore, overexpression of AR in the Sertoli cells up-regulated the expression of N-cadherin, -catenin, ZO-1 and down-regulated vimentin expression. Their expression after heat treatment could be rescued by the AR overexpression. These results indicate that the decreased AR expression after heat treatment is involved in heat-induced cell junction disruption.