title: 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 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 (ZO-1), N-Cadherin, E-Cadherin, α-Catenin, and β-Catenin) was partially rescued. AR knockdown by RNAi 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. The results of an in vivo AR antagonist injection experiment further showed that the recovery of BTB permeability induced by temporal heat stress was regulated by the AR. Furthermore, we observed that the co-localization and interactions of partitioning-defective protein (Par) 6-Par3-aPKC-Cdc42 polarity complex components were disrupted in both AR-knockdown and heat-induced SCs. AR overexpression in SCs prevented the disruption of these protein-protein interactions after heat treatment. AR knockdown or treatment with flutamide in SCs inhibited the restoration of these protein-protein interactions after heat treatment compared with heat treatment alone. Together, these results demonstrate that the AR plays a crucial role in the heat-induced reversible change in BTB via the Par polarity complex.
authors.forename: Xi-Xia
authors.initials: XX
authors.lastname: Li
authors.forename: Su-Ren
authors.initials: SR
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Yang
authors.forename: Shao-Yang
authors.initials: SY
authors.lastname: Ji
authors.forename: Qing
authors.initials: Q
authors.lastname: Wen
authors.forename: Qiao-Song
authors.initials: QS
authors.lastname: Zheng
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhao-Yuan
authors.initials: ZY
authors.lastname: Hu
authors.forename: Xing-Xu
authors.initials: XX
authors.lastname: Huang
authors.forename: Yi-Xun
authors.initials: YX
authors.lastname: Liu
keywords: Androgens/Androgen receptor; Blood-testis barrier; Heat stress; Sertoli cells; Testis