Studies of the effects of neonatal exposure to genistein on the developing female reproductive system.

Studies have shown that developmental exposure to genistein alters murine reproductive differentiation, resulting in abnormal ovarian development (multioocyte follicles) and uterine neoplasia later in life. Further, reproductive function was altered. Prolonged estrous cyclicity was observed following neonatal genistein treatment (0.5-50 mg/kg) on Days 1-5 with dose- and age-related increase in severity. Fertility, determined at 2, 4, and 6 months, showed decreased numbers of genistein-treated females (0.5 or 5 mg/kg) delivering live pups and reduced numbers of pups. At 6 months, 60% of 0.5 mg/kg and 40% of 5 mg/kg groups delivered live pups compared to 100% of controls. At 2 months, half the mice treated with 25 mg/kg of genistein and none treated with 50 mg/kg delivered live pups, although half of the latter group showed signs of pregnancy with few small implantation sites. Ovarian function was disrupted in the low genistein-dosed mice with increased numbers of corpora lutea (CLs) compared to controls and increased ovulated oocytes following exogenous gonadotropins treatment. In contrast, mice treated with high genistein doses had decreased numbers of CLs; ovulation could be restored with exogenous gonadotropins. Thus, neonatal treatment with genistein at environmentally relevant doses caused adverse consequences on ovarian development and reproductive function.