The Heat-Induced Reversible Change in the Blood-Testis Barrier (BTB) Is Regulated by the Androgen Receptor (AR) via the Partitioning-Defective Protein (Par) Polarity Complex in the Mouse

ABSTRACT Scrotal hypothermia is essential for normal spermatogenesis, and temporal heat stress causes a reversible disruption of the blood-testis barrier (BTB). Previous studies have shown that androgen receptor (AR) expression in primary monkey Sertoli cells (SCs) was dramatically reduced after temporary heat treatment. However, the mechanisms underlying the heat-induced reversible disruption of the BTB, including whether it is directly regulated by the AR, remain largely unknown. In this study, we demonstrated that the AR acts upstream to regulate the heat-induced reversible change in the BTB in mice. When the AR was overexpressed in SCs using an adenovirus, the heat stress-induced down-regulation of BTB-associated proteins (zonula occludens-1, N-cadherin, E-cadherin, alpha-catenin, and beta-catenin) was partially rescued. AR knockdown by RNA interference or treatment with flutamide (an AR antagonist) in SCs inhibited the recovery of BTB-associated protein expression after 43°C heat treatment for 30 min...