The sensitivity of murine spermiogenesis to miglustat is a quantitative trait: a pharmacogenetic study

摘要: A major event in the post-meiotic development of male germ cells is formation acrosome. This process can be perturbed C57BL/6 mice by administration small molecule miglustat (N-butyldeoxynojirimycin, NB-DNJ). The miglustat-treated produce morphologically abnormal spermatozoa that lack acrosomes and are poorly motile. In mice, used to maintain long-term reversible infertility. contrast, when was evaluated normal men, it did not affect spermatogenesis. To gain more insight into this species difference we have now reproductive effects rabbits, multiple mouse strains interstrain hybrid mice. Male 18 inbred were administered orally or via miniosmotic pumps. Rabbits given compound their food. Fourth-generation bred from FVB/N (which differ response miglustat), also received drug. Data on fertility (natural mating), sperm motility morphology, acrosome status, serum drug levels collected. rabbits induce aberrations shape motility, although level far exceeded (8.4 μM 0.5 μM, respectively). some Swiss Castle lineages cause infertility, severe morphological reduced motility. these only had milder effects. However, strongly disturbed nucleus AKR/J BALB/c a number C57BL/6-related strains. consequences highly variable. Judging grossly spermatozoa, genetically heterogeneous displayed continuous range intermediate responses, distinct either parental spermatogenesis strain-dependent, while ineffective. Evaluation indicated sensitivity quantitative trait. These studies pave way for identifying genetic factors underlying strain/species differences effect miglustat.