A male contraceptive targeting germ cell adhesion.
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.
Mruk
Dolores D
DD
Population Council, Center for Biomedical Research, 1230 York Avenue, New York, New York 10021, USA. d-mruk@popcbr.rockefeller.edu
Wong
Ching-Hang
CH
Silvestrini
Bruno
B
Cheng
C Yan
CY
D000818:Animals; D002448:Cell Adhesion; D003272:Contraceptive Agents, Male; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage / Q000737:chemistry; D005854:Germ Cells / Q000166:cytology*; D006834:Hydrazines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007191:Indazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects
C432482:1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide; D003272:Contraceptive Agents, Male; D006834:Hydrazines; D007191:Indazoles; D005640:Follicle Stimulating Hormone