Resumen
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.
Idioma original | English |
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Páginas (desde-hasta) | 1309-1315 |
Número de páginas | 7 |
Publicación | Human Reproduction |
Volumen | 21 |
N.º | 5 |
DOI | |
Estado | Published - may. 2006 |
Publicado de forma externa | Sí |
Nota bibliográfica
Funding Information:We thank David Smith and Denise Jelfs and co-workers (Department of Biochemistry, University of Oxford, UK) for expert technical assistance, Mohan Masih for excellent histology services, Lee-Anne Tupper for help with morphometric analysis (Department of Human Anatomy and Genetics, University of Oxford, UK), Prof Harry D. Moore (University of Sheffield, Sheffield, UK) for provision of the Mab 18.6 monoclonal antibody, Dr Richard Callaghan (Nuffield Department of Clinical Biochemistry and Cellular Science, University of Oxford, UK) for assistance with histology, and Prof Ilpo Huht-aniemi, Dr Pirjo Pakarinen and Ms Tarja Laiho (University of Turku, Turku, Finland) for analysis of reproductive endocrinology. This study was supported by The Oxford Glycobiology Institute, Oxford GlycoSciences/Celltech UK (C.M.W.) and NIH Grant 1 U01 HD45861 (F.M.P. and A.C.S.).
ASJC Scopus Subject Areas
- Reproductive Medicine
- Obstetrics and Gynaecology