Disruption of blood-testis barrier dynamics in ether-lipid-deficient mice |
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Authors: | Dorde Komljenovic Roger Sandhoff Andre Teigler Hans Heid Wilhelm W Just Karin Gorgas |
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Institution: | (1) Department of Anatomy and Medical Cell Biology, University of Heidelberg, Heidelberg, Germany;(2) Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany;(3) Heidelberg Center of Biochemistry (BZH), University of Heidelberg, Heidelberg, Germany;(4) Department of Cell Biology, German Cancer Research Center, Heidelberg, Germany;(5) Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany |
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Abstract: | One of the major roles of Sertoli cells is to establish the blood-testis (Sertoli cell) barrier (BTB), which is permanently
assembled and disassembled to accommodate the translocation of leptotene spermatocytes from the basal into the adluminal compartment
of the seminiferous epithelium and to guarantee completion of meiosis and spermiogenesis. Recently, we have demonstrated spermatogenesis
to be arrested before spermatid elongation in Gnpat-null mice with selective deficiency of ether lipids (ELs) whose functions are poorly understood. In this study, we have focused
on the spatio-temporal expression of several BTB tight-junctional proteins in the first wave of spermatogenesis to obtain
insights into the physiological role of ELs during BTB establishment and dynamics. Our data confirm the transient existence
of Russell’s intermediate or translocation compartment delineated by two separate claudin-3-positive luminal and basal tight
junctions and reveal that EL deficiency blocks BTB remodeling. This block is associated with (1) downregulation and mistargeting
of claudin-3 and (2) impaired BTB disassembly resulting in deficient sealing of the intermediate compartment as shown by increased
BTB permeability to biotin. These results suggest that ELs are essential for cyclic BTB dynamics ensuring the sluice mechanism
for leptotene translocation into the adluminal compartment.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
This work was supported by the German Research Foundation (grants Go 432/2-1, Ju 166/3-1, and Sa 172/1-1). |
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Keywords: | Ether lipids Blood-testis (Sertoli cell) barrier Claudins Intermediate compartment Spermatogenic arrest Mouse knockout (Gupat-null) |
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