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The objective of the present study was to determine if exposure to the phytoestrogen genistein (GEN) during immune development had any effects on the production of IgE by adult mice following dermal treatment with trimellitic anhydride (TMA), a respiratory allergen. B6C3F1 mice were exposed to GEN either by feeding at 500 ppm or by gavage (20 mg/kg) for varied periods from gestation day (GD) 14 to postnatal day (PND) 84. In utero exposure to GEN by feeding increased the production of IgE at PND 84 in male mice but not in female mice. In male mice, continuous exposure to GEN postnatally diminished the in utero exposure-induced enhancement in serum total IgE production. However, continuous exposure to GEN from GD 14 to PND 84 was required to increase serum total IgE production in female mice. In utero exposure to GEN by gavage increased the production of IgE at PND 84 in female mice but not in male mice when the mice were maintained on the NIH-07 rodent diet in which a medium level of phytoestrogens was present. The enhancement in IgE production after GEN exposure in females but not in males was associated with decreases in the percentages of CD4(+)CD25(+) T suppressor cells, and increases in the natural killer (NK) cell activity, the basal splenocyte proliferation, the expression of CD86 by B cells, and the production of IL-2 and IL-4. Overall, the results demonstrated that GEN differentially modulated the developing immune system in male and female mice, and that more IgE was produced upon exposure to TMA in the adult.

toxicological sciences

Genistein Enhancement of Respiratory Allergen Trimellitic Anhydride-induced IgE Production by Adult B6C3F1 Mice Following In Utero and Postnatal Exposure