Androgen Receptor Regulation of Germ Cell Migration across Sertoli Cell Tight Junctions

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Androgen Receptor Regulation of Germ Cell Migration across Sertoli Cell Tight Junctions

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Title: Androgen Receptor Regulation of Germ Cell Migration across Sertoli Cell Tight Junctions
Author: Smith, Benjamin Evans
Abstract: The blood-testis barrier includes a tight junction barrier between Sertoli cells that restricts solutes of varying size and charge from crossing the paracellular space thus enabling the formation of unique microenvironments within seminiferous tubules and providing immune privilege to meiotic and postmeiotic cells. Remarkably, large syncytial chains of germ cells are able to transit the Sertoli cell tight junctions (SCTJs) without compromising their integrity. We studied how germ cell cysts migrate across the SCTJs using confocal microscopy to visualize the interplay of SCTJ components during the transit event. Consequently, we were able to determine that the germ cells accomplish this remarkable feat by becoming briefly enclosed within a network of transient compartments fully­bounded by old tight junctions on the adluminal side and new tight junctions on the basal side. We also found that claudin-3 (CLDN3), a tight junction protein, is transiently incorporated into new tight junctions and that formation of new tight junctions is disrupted in mice lacking androgen signaling in somatic Sertoli cells. We followed up on these initial discoveries by generating mice that had floxed Cldn3 locus. To our surprise, we found that Cldn3 knockout mice were fertile and had an intact SCTJ barrier. We then further investigated the expression of tight junction components in mice lacking androgen signaling in somatic Sertoli cells, and found that several tight junction components we down-regulated in these mice in addition to Cldn3, including Cldn13, Cldn20, Tjp1 and Tjp2 isoform C.
Description: Thesis (Ph.D.)--University of Washington, 2012
URI: http://hdl.handle.net/1773/20653
Author requested restriction: No embargo

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