Adjudin, a potential male contraceptive, exerts its effects locally in the seminiferous epithelium of mammalian testes

Reproduction. 2011 May;141(5):571-80. doi: 10.1530/REP-10-0464. Epub 2011 Feb 9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Contraceptive Agents, Male / pharmacology*
  • Contraceptive Agents, Male / toxicity
  • Humans
  • Hydrazines / pharmacology*
  • Hydrazines / toxicity
  • Indazoles / pharmacology*
  • Indazoles / toxicity
  • Indenes / pharmacology
  • Male
  • Piperidines / pharmacology
  • Seminiferous Epithelium / drug effects*
  • Sertoli Cells / drug effects
  • Spermatogenesis / drug effects*
  • Spermatozoa / drug effects*

Substances

  • 1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide
  • CDB 4022
  • Contraceptive Agents, Male
  • Hydrazines
  • Indazoles
  • Indenes
  • Piperidines
  • gamendazole