Anchoring junctions as drug targets: Role in contraceptive development
Mruk,Dolores D.; Silvestrini,Bruno; Cheng,Chuen-yan
Pharmacological Reviews 60(2): 146-180
Publication date: 2008
In multicellular organisms, cell-cell interactions are mediatedin part by cell junctions, which underlie tissue architecture.Throughout spermatogenesis, for instance, preleptotene leptotenespermatocytes residing in the basal compartment of the seminiferousepithelium must traverse the blood-testis barrier to enter theadluminal compartment for continued development. At the sametime, germ cells must also remain attached to Sertoli cells,and numerous studies have reported extensive restructuring atthe Sertoli-Sertoli and Sertoli-germ cell interface during germcell movement across the seminiferous epithelium. Furthermore,the proteins and signaling cascades that regulate adhesion betweentesticular cells have been largely delineated. These findingshave unveiled a number of potential "druggable" targets thatcan be used to induce premature release of germ cells from theseminiferous epithelium, resulting in transient infertility.Herein, we discuss a novel approach with the aim of developinga nonhormonal male contraceptive for future human use, one thatinvolves perturbing adhesion between Sertoli and germ cellsin the testis.