title: Adjudin, a potential male contraceptive, exerts its effects locally in the seminiferous epithelium of mammalian testes.
abstract: Adjudin is a derivative of 1H-indazole-3-carboxylic acid that was shown to have potent anti-spermatogenic activity in rats, rabbits, and dogs. It exerts its effects most notably locally in the apical compartment of the seminiferous epithelium, behind the blood-testis barrier, by disrupting adhesion of germ cells, most notably spermatids to the Sertoli cells, thereby inducing release of immature spermatids from the epithelium that leads to infertility. After adjudin is metabolized, the remaining spermatogonial stem cells and spermatogonia repopulate the seminiferous epithelium gradually via spermatogonial self-renewal and differentiation, to be followed by meiosis and spermiogenesis, and thus fertility rebounds. Recent studies in rats have demonstrated unequivocally that the primary and initial cellular target of adjudin in the testis is the apical ectoplasmic specialization, a testis-specific anchoring junction type restricted to the interface between Sertoli cells and elongating spermatids (from step 8 to 19 spermatids). In this review, we highlight some of the recent advances and obstacles regarding the possible use of adjudin as a male contraceptive.
authors.affiliation: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Ka-Wai
authors.initials: KW
authors.lastname: Mok
authors.forename: Dolores D
authors.initials: DD
authors.lastname: Mruk
authors.forename: Pearl P Y
authors.initials: PP
authors.lastname: Lie
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: Lui
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D003272:Contraceptive Agents, Male / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology* / Q000633:toxicity; D007191:Indazoles / Q000494:pharmacology* / Q000633:toxicity; D007192:Indenes / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D012670:Seminiferous Epithelium / Q000187:drug effects*; D012708:Sertoli Cells / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*
chemical_list: C432482:1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide; C435918:CDB 4022; D003272:Contraceptive Agents, Male; D006834:Hydrazines; D007191:Indazoles; D007192:Indenes; D010880:Piperidines; C530949:gamendazole