Adjudin disrupts spermatogenesis via the action of some unlikely partners: Eps8, Arp2/3 complex, drebrin E, PAR6 and 14-3-3.

Spermatogenesis
C Yan ChengBruno Silvestrini

Abstract

Adjudin, 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (formerly called AF-2364), is a potent analog of lonidamine [1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid] known to disrupt germ cell adhesion, most notably elongating and elongated spermatids, in the seminiferous epithelium of adult rat testes and thus, leads to infertility in rats. Since the population of spermatogonia and spermatogonial stem cells (SSCs) in the seminiferous tubules is not significantly reduced by the treatment of rats with adjudin, adjudin-induced infertility is highly reversible, which enables reinitiation of spermatogenesis and germ cell re-population of the voided seminiferous epithelium. Furthermore, adjudin appears to exert its effects at the testis-specific atypical adherens junction (AJ) type known as ectoplasmic specialization (ES), most notably the apical ES at the Sertoli cell-spermatid interface. Thus, the hypothalamic-pituitary-gonadal axis is not unaffected and systemic side-effects are minimal. This also makes adjudin a potential candidate for male contraceptive development. Herein, we critically evaluate recent findings in the field and provide an updated model regarding the mechanism underlying adjudin-induced apical ES disr...Continue Reading

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Citations

Sep 22, 2012·Contraception·Regine Sitruk-WareDaniel R Mishell
May 7, 2013·Trends in Molecular Medicine·Hin-Ting WanC Yan Cheng
May 15, 2013·Asian Journal of Andrology·Xiaojing QianC Yan Cheng
Mar 2, 2013·The Journal of Endocrinology·Elizabeth I TangC Yan Cheng
Jan 24, 2013·Critical Reviews in Biochemistry and Molecular Biology·Wenhui SuC Yan Cheng
Jan 23, 2016·Seminars in Cell & Developmental Biology·Elizabeth I TangC Yan Cheng
May 21, 2013·Spermatogenesis·Xiaojing QianC Yan Cheng
Dec 26, 2013·Bioorganic & Medicinal Chemistry Letters·Fern E Murdoch, Erwin Goldberg
Oct 25, 2016·Autoimmunity Reviews·Darja Kanduc, Yehuda Shoenfeld
May 23, 2013·The Journal of Biological Chemistry·Mouna A MikatiEmil Reisler
Aug 28, 2014·American Journal of Physiology. Endocrinology and Metabolism·N Ece Gungor-OrdueriC Yan Cheng
Oct 18, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Elissa W P WongC Yan Cheng

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