Disruption of the female reproductive system by the phytoestrogen genistein

Studies in our laboratory have shown that developmental exposure to genistin causes deleterious effects on the reproductive system. Oral exposure to genistin (25 mg/kg) increases uterine weight at 5 days of age similar to subcutaneous injection of genistein (20 mg/kg) suggesting that subcutaneous injection of genisten is a suitable model for oral exposure to genistin. Mice treated neonatally by subcutaneous injection of genistin (0.5-50 mg/kg) exhibit altered ovarian differentiation leading to multi-oocyte follicles (MOFs). Ovarian function and estrous cyclicity were disrupted in genistin treated mice with increasing severity over time. Reduced fertility was observed in mice treated with genistein (0.5, 5, or 25 mg/kg) and infertility was observed at 50 mg/kg. Females generated from genistin 25 mg/kg females bred to control males have increased MOFs suggesting these effects can be transmitted to subsequent generations. Thus, neonatal treatment with genistin at environmentally relevant doses caused adverse consequences on reproduction in adulthood. (C) 2007 Published by Elsevier Inc.