Gender-based differences in rats after chronic dietary exposure to genistein.

Gender-based differences can be observed from pharmacokinetic, behavioral, or anatomical assessments. No single assessment tool will provide a complete answer, but the use of a variety of indices, each with known gender-related outcome differences, can reveal agent-induced gender-based alterations. In a series of initial range-finding studies in rats conducted at the National Center for Toxicological Research (NCTR), the effects of dietary exposure to the weak estrogen, genistein, have been assessed using a number of techniques with validated gender-related outcome measures. The findings indicated that (1) the internal dose of genistein was higher in females than males after equivalent dietary exposure and this was consistent with the faster rate of genistein elimination in males; (2) in behavioral assessments, males and females in the high-dose dietary genistein group consumed more of a sodium-flavored solution; however, no genistein-related changes were observed in open field or running wheel activity, play behavior, or intake of a saccharin-flavored solution; and (3) dose-related alterations of the volume of the sexually dimorphic nucleus of the medial preoptic area were observed in genistein-exposed male rats but not females. These observations describe the utility of a variety of gender-based assessment tools and indicate that dose-related effects of developmental and chronic dietary exposure to genistein can be observed in the rodent. Additional studies, perhaps in nonhuman primates, are necessary to further predict the effect(s) of genistein on human gender-based development.