Regulation and characterization of the ATP-binding cassette transporter-B1 in the epididymis and epididymal spermatozoa of the rat

Abstract

It has been reported that following administration, alkylphenols, such as octylphenol, reach the testis and epididymis but fail to accumulate in these tissues, suggesting the rapid expulsion of these chemicals by transporters. Specialized transporters that function to restrict compounds that enter target cells have been identified. ABCB1 is a member of the ATP-binding cassette family of proteins capable of transporting a broad range of drugs and xenobiotics out of tissues. The objective of this study was to characterize the expression profile and functional role of ABCB1a and ABCB1b along the different regions (initial segment, caput, corpus [CS], and cauda [CA]) of the adult rat epididymis. ABCB1a and ABCB1b transcripts were detected in all four regions of the epididymis. Immunolocalization revealed minimal ABCB1 staining in epithelial cells or spermatozoa of proximal regions of the epididymis; however, this progressively increased in the CS and CA epididymis. This expression gradient was confirmed by Western blot, suggesting that spermatozoa acquire ABCB1 during epididymal maturation. Multidrug resistance (MDR) assays revealed that rat epididymal cells and epididymal spermatozoa display an MDR phenotype that can be inhibited under control conditions. To assess whether or not the system was inducible by alkylphenols, cells from an immortalized epididymal cell line (RCE) were exposed to different concentrations of nonylphenol. Results revealed a significant induction of both ABCB1a and ABCB1b messenger RNA and ABCB1 protein in RCE cells. Our findings demonstrate a role for ABCB1 in protecting both epididymal principal cells and spermatozoa from xenobiotics. © The Author 2010. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.