Objectives: The adverse reproductive effects of phytoestrogens reported for animals are of concern to humans because of the ubiquitous presence of these compounds in food staples. It is possible that phytoestrogens exert similar adverse effects in humans. Previous studies investigating the effects of phytoestrogens have utilized pharmacological doses and parenteral administration. Although these modes of treatment demonstrate the inherent potency of phytoestrogens, they provide little insight into the consequences of chronic low dose exposure that is likely to be characteristic of the natural situation. The objective of this study was to examine reproductive sequelae at critical periods of development in rats following chronic dietary exposure to phytoestrogens at doses relevant to human exposures.Design: Developmental, hormonal and reproductive parameters were evaluated in female rats before and after attainment of puberty following exposure to genistein (G) in utero and throughout life.Materials and Methods: Twelve pregnant rats were fed G diet (50 μg/day) from day 17 of gestation, and eight were fed a control diet without G. Pups were weaned on day 21 and only female rats were used in this study. Four litters/group were euthanized on day 21; hormones and reproductive organs were evaluated. On day 21, four litters of genistein-treated (GT) rats were placed on control diet (Ex-G), and the remaining four continued on G diet. Time of vaginal opening was determined and daily vaginal smears were taken to evaluate estrous cyclicity. All rats were euthanized in proestrus stage around day 70 of age. Blood was collected for hormone measurement by RIA. Weights of ovaries and reproductive tracts were recorded and tissues processed for histopathology.Results: At birth, number of pups/litter and body weights (BW) were not different between GT and control pups. At day 21, BW, ovarian and reproductive tract weights of GT rats were not different from those of controls. However, there was a significant reduction in serum estradiol (E 2 : 39±17 pg/ml) and progesterone (P 4 : 12±6 ng/ml) levels in GT rats compared to controls (E 2 : 366±41 pg/ml; P 4 : 128±15 ng/ml). FSH level was similar between GT and control rats. Vaginal opening occurred around day 35 in all groups. More irregular cycles were observed in GT and Ex-G rats compared to controls. At day 70, serum E 2 , P 4 and FSH were similar in all groups. Atretic follicles and secondary interstitial glands were seen more frequently in GT and Ex-G rats compared to controls. Hypertrophy of the rete ovarii was observed in GT and Ex-G rats; rete ovarii was cystic in some GT rats.Conclusion: Our data suggest that exposure to dietary levels of genistein may adversely affect female reproductive processes particularly if exposure occurs early in life. The long-term effects of this exposure regimen on fertility and fecundity are unknown and require further studies.