Persistent immunological consequences of gestation zinc deprivation

Recent work has shown that offspring of outbred mice deprived of adequate dietary zinc during the latter two-thirds of gestation exhibited a defective direct plaque-forming cell response to immunization with heterologous erythrocytes, as well as impaired ontogenesis of serm IgM. Moreover, such aberrant immunological measurements continued to be observed, although to a lesser degree, in F₂ and F₃ progeny. We now demonstrate that offspring of mice moderately deprived of zinc (5 ppm zinc diet) between days 7 and 20 of gestation also show an aberrant pattern of development of serum levels of IgG(2a), and IgA, despite complete nutritional rehabilitation beginning at birth. Only by 6 months of age were concentrations of these serum immunoglobulins similar to those in offspring of control dams. In contrast, levels of IgG₁ and IgG(2b) were within normal ranges by 6 weeks of age. Cross-fostering of zinc-deprived offspring to dams adequately nourished during pregnancy did little to ameliorate their aberrant pattern of serum immunoglobulin development. Defective maturation of serum IgG(2a) and IgA did not persist in F₂ and F₃ progeny. Nonetheless such 2nd and 3rd generation offspring continued to have higher than normal perinatal mortality. The alterations of immune ontogenesis in these mice could not be attributed to the persistence of abnormal plasma zinc levels, as these were within normal ranges. It would appear that zinc deficiency during gestation may alter the basic mechanism of development of immunological competence.