Observations on Offspring of Mice Made Diabetic With Streptozocin

My objective was to determine the effect of streptozocin (STZ)-induced diabetes in male inbred mice on nonfasting blood glucose levels and body weights of offspring. Hyperglycemia was induced in CBA/H male mice by either multiple subdiabetogenic doses (MD) of STZ (5 doses/day of 50 mg STZ/kg body wt) or by a single high sublethal (SD) dose (200 mg STZ/kg body wt). Females were made diabetic by the multiple low-dose procedure. The following matings were set up: SD males with normal (NOR) females; MD males with NOR females; NOR males with MD females; MD males with MD females. Controls were matings of NOR males with NOR females. Among the first cohort of litters was born one female from the cross of an SD male with an NOR female who became spontaneously hyperglycemic at 5 wk of age; the female progeny of this cross had significantly lower body weights. All other progeny groups were normoglycemic (up to 5 wk) and had normal body weights. Test progeny weaned in the second and subsequent cohorts of litters were also normoglycemic. The major effect in this progeny group was on body weight; diabetic fathers (particularly MD males) mated with NOR females produced offspring with significantly higher juvenile body weights than the controls (increase of ∼0.5 g). These body-weight distributions also appeared more homogeneous than the more variable body-weight distribution of the controls. In contrast, MD mothers (mated with NOR males) produced second-cohort offspring with significantly lower average body weights (decrease of ∼1–2 g) than the controls. However, if MD females were mated with MD males, the second-cohort offspring had body-weight distributions that approached those observed in control progeny or in progeny where the father alone was diabetic. The mechanism and biological significance of this complex STZ-induced paternal transmission effect is unknown, although general possibilities are discussed.