Adjudin, a potential male contraceptive, exerts its effects locally in the seminiferous epithelium of mammalian testes
Open Access
- 1 May 2011
- journal article
- review article
- Published by Bioscientifica in Reproduction
- Vol. 141 (5), 571-580
- https://doi.org/10.1530/rep-10-0464
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.Keywords
This publication has 85 references indexed in Scilit:
- Restricted Arp3 expression in the testis prevents blood–testis barrier disruption during junction restructuring at spermatogenesisProceedings of the National Academy of Sciences of the United States of America, 2010
- A nucleator arms race: cellular control of actin assemblyNature Reviews Molecular Cell Biology, 2010
- Cytokines and junction restructuring events during spermatogenesis in the testis: An emerging concept of regulationCytokine & Growth Factor Reviews, 2009
- Cadmium-induced testicular injuryToxicology and Applied Pharmacology, 2009
- Coordinating cellular events during spermatogenesis: a biochemical modelTrends in Biochemical Sciences, 2009
- An intracellular trafficking pathway in the seminiferous epithelium regulating spermatogenesis: a biochemical and molecular perspectiveCritical Reviews in Biochemistry and Molecular Biology, 2009
- Epidermal growth factor receptor pathway substrate 8 (Eps8) is a novel regulator of cell adhesion and the blood‐testis barrier integrity in the seminiferous epitheliumThe FASEB Journal, 2009
- Biology and regulation of ectoplasmic specialization, an atypical adherens junction type, in the testisBiochimica et Biophysica Acta (BBA) - Biomembranes, 2008
- Ectoplasmic specialization: a friend or a foe of spermatogenesis?BioEssays, 2006
- The ARP2/3 complex: an actin nucleator comes of ageNature Reviews Molecular Cell Biology, 2006