Gamete Biology

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

Abstract
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 non-hormonal male contraceptives, a comprehensive examination of their effects on male reproduction is necessary. To this end we have 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 also 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. While the deformed spermatozoa from the testis were able to activate oocytes very efficiently, those from the cauda epididymis often failed to do so. This problem was overcome when the sperm-injected oocytes were treated with a parthenogenic agent, Sr²⁺. Oocytes, injected with the misshapen spermatozoa from NB-DNJ- and NB-DGJ-treated mice, developed (with or without Sr²⁺-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.

Key words: Gamete Biology • Assisted Reproductive Technology • Calcium • Fertilization • Sperm maturation

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