Figure 4

Quantitation of effects of miglustat on morphology of spermatozoa from inbred mouse strains and interstrain hybrid mice. Effects of miglustat administration on morphological features of cauda epididymal spermatozoa from (A and B) mice of various inbred strains (n = 2–3 per strain) and from (C and D) fourth-generation C57BL/6 × FVB/N hybrid mice. In (A and C) spermatozoa were scored for possession of an acrosome (present/absent), irrespective of acrosomal staining pattern, and for possession of a grossly abnormal non-falciform nucleus. In (B and D) spermatozoa were scored for acrosomal staining pattern (normal/abnormal), and for the normality of their nuclear morphology. Falciform nuclei (flat and curved) that deviated from the typical shape of spermatozoa from untreated mice were score as abnormal. In (C and D) data are presented from the hybrid mice that were most affected by miglustat, and from a representative number of hybrid mice that showed a lesser response. Each datapoint in (A and B) expresses the difference between the average score of drug-treated mice from one inbred strain and the average score of control mice of the same strain. Each datapoint in (C and D) expresses the difference between the score of one drug-treated hybrid mouse and the average score of untreated FVB/N mice. Data points were fitted by linear regression; the corresponding trend lines are displayed in grey (correlation coefficients in A, B, C and D were 0.97, 0.79, 0.98 and 0.84, respectively). Miglustat administration was at 150 mg/kg/day, except SM/J mice (15 mg/kg/day). At least 200 spermatozoa per mouse were scored for nuclear morphology and acrosomal staining.