Anchoring junctions as drug targets: role in contraceptive development.
In multicellular organisms, cell-cell interactions are mediated in part by cell junctions, which underlie tissue architecture. Throughout spermatogenesis, for instance, preleptotene leptotene spermatocytes residing in the basal compartment of the seminiferous epithelium must traverse the blood-testis barrier to enter the adluminal compartment for continued development. At the same time, germ cells must also remain attached to Sertoli cells, and numerous studies have reported extensive restructuring at the Sertoli-Sertoli and Sertoli-germ cell interface during germ cell movement across the seminiferous epithelium. Furthermore, the proteins and signaling cascades that regulate adhesion between testicular cells have been largely delineated. These findings have unveiled a number of potential "druggable" targets that can be used to induce premature release of germ cells from the seminiferous epithelium, resulting in transient infertility. Herein, we discuss a novel approach with the aim of developing a nonhormonal male contraceptive for future human use, one that involves perturbing adhesion between Sertoli and germ cells in the testis.
Mruk
Dolores D
DD
Population Council, Center for Biomedical Research, The Mary M Wohlford Laboratory for Male Contraceptive Research, 1230 York Avenue, New York, NY 10065, USA. d-mruk@popcbr.rockefeller.edu
Silvestrini
Bruno
B
Cheng
C Yan
CY
D022005:Adherens Junctions / Q000502:physiology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology*; D008297:Male; D012708:Sertoli Cells / Q000502:physiology / Q000648:ultrastructure; D013090:Spermatocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000378:metabolism* / Q000648:ultrastructure
D003272:Contraceptive Agents, Male