Circulating levels of genistein in the neonate, apart from dose and route, predict future adverse female reproductive outcomes

Developmental exposure to estrogenic compounds can disrupt sexual differentiation and adult reproductive function in many animals including humans. Phytoestrogens (plant estrogens) in the diet comprise a significant source of estrogenic exposure to humans, particularly in infants who are fed soy-based infant formula. Animal models have been developed to test the effects of phytoestrogen exposure on the developing fetus and neonate. Here we review studies quantifying the amount of phytoestrogen exposure in human adults and infants and discuss the few available epidemiological studies that have addressed long-term consequences of developmental phytoestrogen exposure. We then describe in detail rodent models of developmental exposure to the most prevalent phytoestrogen in soy products, genistein, and the effects of this exposure on female reproductive function. These models have used various dosing strategies to mimic the phytoestrogen levels in human populations. Serum circulating levels of genistein following each of the models and their correlation to reproductive outcomes are also discussed. Taken together, the studies clearly demonstrate that environmentally relevant doses of genistein have significant negative impacts on ovarian differentiation, estrous cyclicity, and fertility in the rodent model. Additional studies of reproductive function in human populations exposed to high levels of phytoestrogens during development are warranted.