Neonatal Genistein Exposure Causes Implantation Failure by Disrupting Uterine Developmental Patterning and Endometrial Gland Formation

Female mice exposed neonatally to the phytoestrogen genistein (GEN) at doses similar to those in infants consuming soy-based infant formulas are infertile due in part to uterine implantation defects. To determine the mechanisms by which neonatal GEN exposure causes implantation defects, female mice were exposed to vehicle (corn oil) or GEN in corn oil (50 mg/kg/day) on postnatal days (PND) 1-5. Uterine tissues were collected during early gestation for microarray analysis; gestation day 1.5 (GD1.5), GD3.5, GD4.5 and GD5.5. We conclude that neonatal GEN exposure disrupts expression of genes important for uterine development, causing posteriorization and diminished gland function during pregnancy that together cause implantation failure. CD-1 mice were exposed to corn oil as controls (CON) or genistein (GEN) at a dose of 50 mg/kg/day on postnatal days 1-5. Uteri were collected on gestation day 1.5 (GD1.5), GD3.5, GD4.5 or GD5.5