A male contraceptive targeting germ cell adhesion.

Abstract

Throughout spermatogenesis, developing germ cells remain attached to Sertoli cells via testis-specific anchoring junctions. If adhesion between these cell types is compromised, germ cells detach from the seminiferous epithelium and infertility often results. Previously, we reported that Adjudin is capable of inducing germ cell loss from the epithelium. In a small subset of animals, however, oral administration of Adjudin (50 mg per kg body weight (b.w.) for 29 d) resulted in adverse effects such as liver inflammation and muscle atrophy. Here, we report a novel approach in which Adjudin is specifically targeted to the testis by conjugating Adjudin to a recombinant follicle-stimulating hormone (FSH) mutant, which serves as its 'carrier'. Using this approach, infertility was induced in adult rats when 0.5 microg Adjudin per kg b.w. was administered intraperitoneally, which was similar to results when 50 mg per kg b.w. was given orally. This represents a substantial increase in Adjudin's selectivity and efficacy as a male contraceptive.

• Authors: Dolores D Mruk, Ching-Hang Wong, Bruno Silvestrini, C Yan Cheng
• Journal: Nature medicine (Nat Med) Vol. 12 Issue 11 Pg. 1323-8 (Nov 2006) ISSN: 1078-8956 [Print] United States
• PMID: 17072312 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide
• Contraceptive Agents, Male
• Hydrazines
• Indazoles
• Follicle Stimulating Hormone

Topics

• Animals
• Cell Adhesion
• Contraceptive Agents, Male
• Follicle Stimulating Hormone (administration & dosage, chemistry)
• Germ Cells (cytology)
• Hydrazines (administration & dosage, chemistry, pharmacokinetics, pharmacology)
• Indazoles (administration & dosage, chemistry, pharmacokinetics, pharmacology)
• Male
• Rats
• Rats, Sprague-Dawley
• Testis (drug effects)