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Abstract

Unraveling the molecular targets pertinent to junction restructuring events during spermatogenesis using the Adjudin-induced germ cell depletion model (PDF) (HTML
Xia,Weiliang; Mruk,Dolores D.; Lee,Will M.; Cheng,Chuen-yan
Journal of Endocrinology 192(3): 563-583
Publication date: 2007



During spermatogenesis, extensive restructuring takes placeat the Sertoli-Sertoli and Sertoli-germ cell interface,which is regulated via intriguing interactions among cytokines,proteases, protease inhibitors, kinases, phosphatases, and transcriptionfactors. This in turn determines the steady-state levels ofintegral membrane proteins at the cell junctions. We soughtto further expand these observations using the Adjudin model.Adjudin is a potential male contraceptive that targets Sertoli-germcell adhesion, causing exfoliation of spermatids and spermatocytes,but not spermatogonia, from the seminiferous epithelium. Thismodel thus provides the means to identify crucial regulatorymolecules and signaling pathways pertinent to junction restructuringevents during spermatogenesis. In this study, genome-wide expressionprofiling of rat testes after treatment with Adjudin at thetime of extensive junction restructuring was performed. Differentiallyregulated genes, such as cytokines, proteases, protease inhibitors,cell junction-associated proteins, and transcription factorspertinent to junction restructuring were identified. These datawere consistent with earlier findings; however, much new informationwas obtained which has been deposited at the Gene ExpressionOmnibus data repository website: http://www.ncbi.nih.gov/geo/with Accession number: GSE5131 [NCBI GEO] . The primary signaling eventspertinent to junction restructuring in the testis induced byAdjudin were also delineated using bioinformatics. These findingswere also consistent with recently published reports. The identifiedmolecular signatures or targets pertinent to junction dynamicsin the testis as reported herein, many of which have not beeninvestigated, thus offer a framework upon which the regulationof junction restructuring events at the Sertoli-Sertoliand Sertoli-germ cell interface pertinent to spermatogenesiscan be further studied.




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