Endocrine disrupters, chemicals that mimic or block the actions of endogenous hormones, have been implicated in the increased incidence of birth defects associated with androgen-dependent development. Phytoestrogens (i.e., plant-derived endocrine disrupters) are an increasingly popular source of protein in human diets, although their effects on androgen-dependent development are not as well characterized as those of synthetic endocrine disrupting compounds. Congenital abnormalities of the human male reproductive system are increasing in incidence in the U.S., as is the consumption of soy products. This correlation has lead to speculation that phytoestrogen exposure in utero or during early life contributes to common birth defects in boys. The studies proposed in this application will provide a better understanding of the impact of phytoestrogen consumption on male-typic development during critical periods of masculinization of both the reproductive system, and sexually dimorphic, non-reproductive behaviors such as learning, memory and anxiety. Female rats will be randomly assigned to one of the following groups; (1) no genistein treatment during gestation or lactation (control group), (2) genistein treatment during gestation only (gestation group), (3) genistein treatment during lactation only (lactation group), and (4) genistein treatment during both gestation and lactation (perinatal group). Male rat pups exposed to genistein in utero and/or via nursing from their treated mothers as well as control animals will be followed into adulthood and observed for potential problems associated with androgen-dependent development. Mission of NCCAM. The proposed studies fit well with NCCAM's mission at several levels. First, they are designed to test the safety of genistein, a commonly used dietary supplement in humans, on multiple physiologic systems. Second, the proposed studies are constructed to train undergraduate students to conduct scientific research on health-related topics that are associated with dietary supplements. This is in agreement with NCCAM's mission to train new scientists in the science of alternative medicine. Birth defects of the male reproductive system are increasing in incidence in the U.S., as is the consumption of soy products. We propose to identify critical periods during male development when exposure to soy results in abnormalities in development. This knowledge will prove useful in advising pregnant women to limit their intake of soy during pregnancy, if gestational exposure is most deleterious, versus avoiding soy-based infant formulas if lactational exposure results in more ill effects. [unreadable] [unreadable] [unreadable]