Long-term non-hormonal male contraception in mice using N-butyldeoxynojirimycin.
BACKGROUND
The imino sugar N-butyldeoxynojirimycin (NB-DNJ) causes reversible infertility in male mice. This compound may have promise as a male contraceptive, because it is already in clinical use, for a non-reproductive condition. As contraceptives need to be taken for extended periods of time, it was essential to evaluate NB-DNJ for its reproductive effects over a long period of administration.


METHODS
We have assessed the imino sugar for its long-term effects on the fertility of male C57BL/6 mice, reversibility and potential cumulative toxicity by monitoring various reproductive and systemic parameters over 12 months.


RESULTS
Long-term low-dose (15 mg/kg/day) administration of NB-DNJ was sufficient to maintain infertility in male mice. In contrast to short-term drug treatment, imino sugar exposure for more than 3 months resulted in reduced sperm counts. Male mice that had been administered imino sugar for 6, 10 or 12 months and were then maintained without drug administration regained their fertility within 9 weeks after withdrawal of the drug. Prolonged NB-DNJ intake did not affect reproductive hormone levels, serum biochemistry or animal behaviour.


CONCLUSIONS
Low-dose treatment with NB-DNJ over a long period is an effective approach for the regulation of fertility in a male mammal by non-hormonal means, without causing overt adverse effects.
Walden
Charlotte M
CM
The Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, UK.
Butters
Terry D
TD
Dwek
Raymond A
RA
Platt
Frances M
FM
van der Spoel
Aarnoud C
AC
D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003267:Contraception / Q000379:methods*; D003272:Contraceptive Agents, Male / Q000008:administration & dosage*; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D050111:Imino Sugars / Q000008:administration & dosage*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects; D013737:Testis / Q000166:cytology / Q000187:drug effects; D013739:Testosterone / Q000097:blood
D003272:Contraceptive Agents, Male; D050111:Imino Sugars; D017485:1-Deoxynojirimycin; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C059896:miglustat