N -Butyldeoxygalactonojirimycin Induces Reversible Infertility in Male CD Rats.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
    • Abstract:
      This study shows for the first time that an iminosugar exerts anti-spermiogenic effect, inducing reversible infertility in a species that is not related to C57BL/6 male mice. In CD rats, N-butyldeoxygalactonojirimycin ( N B-DGJ) caused reversible infertility at 150 mg/kg/day when administered daily as single oral dose. N B-DGJ inhibited CD rat-derived testicular β-glucosidase 2 (GBA2) activity at 10 µM but did not inhibit CD rat-derived testicular ceramide-specific glucosyltransferase (CGT) at doses up to 1000 µM. Pharmacokinetic studies revealed that sufficient plasma levels of N B-DGJ (50 µM) were achieved to inhibit the enzyme. Fertility was blocked after 35 days of treatment and reversed one week after termination of treatment. The rapid return of fertility indicates that the major effect of N B-DGJ may be epididymal rather than testicular. Collectively, our in vitro and in vivo studies in rats suggest that iminosugars should continue to be pursued as potential lead compounds for development of oral, non-hormonal male contraceptives. The study also adds evidence that GBA2, and not CGT, is the major target for the contraceptive effect of iminosugars.
      Competing Interests: The authors declare no conflict of interest. The research for this article was conducted while Dr. Hild was employed at Bioqual Inc. Her current affiliation is Office of Research Infrastructure Programs, Office of the Director, National Institutes of Health (NIH), Bethesda, MD. The opinions expressed in this article are the author’s own and do not reflect the views of NIH or the Department of Health and Human Services.
    • References:
      Biol Reprod. 2008 Jun;78(6):1139-52. (PMID: 18218611)
      J Biol Chem. 2007 Nov 9;282(45):32655-64. (PMID: 17848577)
      J Clin Invest. 2006 Nov;116(11):2985-94. (PMID: 17080196)
      J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jan 15;877(3):149-54. (PMID: 19095507)
      Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4227-32. (PMID: 11917099)
      J Biol Chem. 1994 Mar 18;269(11):8362-5. (PMID: 8132559)
      Hum Reprod. 2007 Mar;22(3):702-7. (PMID: 17067996)
      J Biol Chem. 2013 Sep 6;288(36):26052-66. (PMID: 23880767)
      Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12147-52. (PMID: 9770454)
      J Acquir Immune Defic Syndr. 1994 Feb;7(2):139-47. (PMID: 7905523)
      Nat Rev Drug Discov. 2002 Jan;1(1):65-75. (PMID: 12119611)
      Endocr Rev. 2008 Jun;29(4):465-93. (PMID: 18436704)
      Reprod Biol Endocrinol. 2007 Jan 22;5:1. (PMID: 17241468)
      J Biol Chem. 2000 Jul 28;275(30):22623-6. (PMID: 10801776)
      Lancet. 2000 Apr 29;355(9214):1481-5. (PMID: 10801168)
      Biol Reprod. 2005 Apr;72(4):805-13. (PMID: 15576825)
      Fertil Steril. 1987 Sep;48(3):459-61. (PMID: 3305087)
      PLoS Genet. 2015 Mar 24;11(3):e1005063. (PMID: 25803043)
      Glycobiology. 2005 Oct;15(10):43R-52R. (PMID: 15901676)
      Reproduction. 2016 Mar;151(3):R29-41. (PMID: 26628556)
      Aust J Biol Sci. 1983;36(4):333-50. (PMID: 6362633)
      Asian J Androl. 2000 Dec;2(4):283-7. (PMID: 11202417)
      Xenobiotica. 2007 Mar;37(3):298-314. (PMID: 17624027)
      Bioorg Med Chem Lett. 2014 Jan 15;24(2):419-24. (PMID: 24368213)
      Biochem Biophys Res Commun. 1998 Oct 20;251(2):557-63. (PMID: 9792812)
      Urol Clin North Am. 2014 Feb;41(1):145-61. (PMID: 24286773)
      Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17173-8. (PMID: 12477936)
      J Org Chem. 2012 Apr 6;77(7):3082-98. (PMID: 22432895)
      J Med Chem. 2010 Jan 28;53(2):689-98. (PMID: 20000679)
      Biol Reprod. 2004 Jul;71(1):348-58. (PMID: 15044265)
      Contraception. 2013 Mar;87(3):296-9. (PMID: 22995542)
      Arch Biochem Biophys. 1987 Sep;257(2):370-8. (PMID: 3662530)
      Biochem Pharmacol. 2000 Apr 1;59(7):821-9. (PMID: 10718340)
      Biol Reprod. 2008 Jun;78(6):1127-38. (PMID: 18218612)
      Biol Reprod. 2001 Dec;65(6):1771-9. (PMID: 11717140)
    • Grant Information:
      HHSN275200503400C and HHSN275201300017C International Eunice Kennedy Shriver National Institute of Child Health and Human Development
    • Contributed Indexing:
      Keywords: NB-DGJ; NB-DNJ; contraceptive; iminosugar
    • Accession Number:
      19130-96-2 (1-Deoxynojirimycin)
      C4XNY919FW (migalastat)
      EC 2.4.1.- (Glucosyltransferases)
      EC 2.4.1.80 (ceramide glucosyltransferase)
      EC 3.2.1.21 (beta-Glucosidase)
    • Publication Date:
      Date Created: 20200108 Date Completed: 20200513 Latest Revision: 20200513
    • Publication Date:
      20240829
    • Accession Number:
      PMC6982022
    • Accession Number:
      10.3390/ijms21010301
    • Accession Number:
      31906257