| Alkylated imino sugars, reversible male infertility-inducing agents, do not affect the genetic integrity of male mouse germ cells during short-term treatment despite induction of sperm deformities. | |
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MedLine Citation:
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PMID: 15576825 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Reversible infertility can be induced in male mice by oral administration of the alkylated imino sugars N-butyldeoxynojirimycin (NB-DNJ) and N-butyldeoxygalactonojirimycin (NB-DGJ). Spermatozoa of these mice have grossly misshapen heads and reduced motility. Because NB-DNJ and related compounds may hold promise as nonhormonal male contraceptives, a comprehensive examination of their effects on male reproduction is necessary. To this end, we further examined reproductive properties of the dysmorphic spermatozoa that are produced after short-term imino sugar administration at the minimal dose that completely abolishes the ability of male C57BL/6 mice to produce offspring by natural mating. Here, we report that, in vitro, the abnormal spermatozoa from the NB-DNJ- and NB-DGJ-treated mice were unable to fertilize oocytes. In addition, we investigated whether the imino sugars damage the genetic integrity of spermatozoa. To test this, we microsurgically injected deformed spermatozoa from imino sugar-treated males into oocytes. The deformed spermatozoa from the testis were able to activate oocytes very efficiently, but those from the cauda epididymis often failed to do so. This problem was overcome when the sperm-injected oocytes were treated with a parthenogenetic agent, Sr(2+). Oocytes injected with the misshapen spermatozoa from NB-DNJ- and NB-DGJ-treated mice developed (with or without Sr(2+) treatment) into live offspring that grew normally and were normally fertile. This indicates that during short-term administration, alkylated imino sugars alter sperm morphology and physiology but do not diminish the genetic potential of spermatozoa. |
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Authors:
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Ryota Suganuma; Charlotte M Walden; Terry D Butters; Frances M Platt; Raymond A Dwek; Ryuzo Yanagimachi; Aarnoud C van der Spoel |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2004-12-01 |
Journal Detail:
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Title: Biology of reproduction Volume: 72 ISSN: 0006-3363 ISO Abbreviation: Biol. Reprod. Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-03-22 Completed Date: 2005-08-30 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0207224 Medline TA: Biol Reprod Country: United States |
Other Details:
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Languages: eng Pagination: 805-13 Citation Subset: IM |
Affiliation:
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Institute for Biogenesis Research, University of Hawaii School of Medicine, Honolulu, Hawaii 96822, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Deoxynojirimycin
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analogs & derivatives*,
pharmacology Alkylation Animals Carbohydrates Contraceptive Agents, Male / pharmacology* Disulfides / metabolism Female Fertility / drug effects, genetics Fertilization in Vitro Imines Infertility, Male / chemically induced, genetics*, pathology Male Mice Mice, Inbred C57BL Mice, Inbred DBA Pregnancy Pregnancy Outcome Protamines / metabolism Spermatozoa / drug effects*, pathology*, physiology Sphingolipids / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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1 U01 HD45861/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carbohydrates; 0/Contraceptive Agents, Male; 0/Disulfides; 0/Imines; 0/N-butyldeoxygalactonojirimycin; 0/Protamines; 0/Sphingolipids; 0/miglustat; 19130-96-2/1-Deoxynojirimycin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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