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Hum. Reprod. Advance Access published online on January 5, 2006
Human Reproduction, doi:10.1093/humrep/dei463
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received October 13, 2005
Revised November 14, 2005
Accepted November 17, 2005

Article

Long-term non-hormonal male contraception in mice using N-butyldeoxynojirimycin

Charlotte M. Walden 1, Terry D. Butters 1, Raymond A. Dwek 1, Frances M. Platt 1, and Aarnoud C. van der Spoel 1 *

1 The Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, UK

* To whom correspondence should be addressed.
Aarnoud C. van der Spoel, E-mail: aarnoud.vanderspoel{at}bioch.ox.ac.uk


  Abstract

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. CONCLUSION: 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.

Keywords: acrosome/behaviour/imino sugar/male contraception/sperm morphology.
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