Neonatal exposure to genistein reduces expression of estrogen receptor alpha and androgen receptor in testes of adult mice

We investigated the long-term estrogenic influence of genistein on the male reproductive system in mice. Newborn ICR male mice were treated with genistein (10, 100, or 1000 mug/mouse) for neonatal 5 days. As positive control, administration of diethylstilbestrol (0.5-50 mug/mouse) was carried out. In mice exposed to genistein,we examined weight of testes, sperm counts, sperm motility, and mRNA expression levels of estrogen receptor alpha (ER alpha) and androgen receptor (AR) at 4, 8 or 12 weeks after birth. Moreover, at 12 weeks of age, we evaluated protein level of ER alpha. In our conventional reproductive-toxicological study (weight of testes, sperm counts and sperm motility), neonatal transient exposure to genistein did not show adverse effects on the male reproductive system in 4, 8 or 12 week old mice. However, in mice treated with genistein mRNA expression levels of ER alpha and AR were reduced at 8 weeks. This reduction was recovered at 12 weeks in mice treated with a lower dose (10 mug) of genistein but not in those with higher doses (100 mug and 1000 mug). In addition, ER alpha protein levels tended to decrease in 12 weeks of adulthood. Our results exhibited that the disruption of gene expression continued for long term such as 3 months after administration of genistein, even if no effect was found at conventional reproductive-toxicological level. We have shown that neonatal administration of weak estrogenic compound (genistein) affects male reproductive organs at molecular levels in adulthood.