Reproductive and toxicological effects of isoflavones on female offspring of rats exposed during pregnancy

We investigated the actions of isoflavones (daidzin + daidzein 22.7%, daidzein 16.9%, genistin + genistein 16.3%, genistein 13.1%) in pregnant rats, assessing possible repercussions regarding the development of female conceptus. Doses of isoflavones, 10 mg/kg or 100 mg/kg, were administered to pregnant rats by oral gavage, from the sixth day of pregnancy until its completion. The pregnant rats exposed to isoflavones at these doses when laparotomized showed alterations in the number of live fetuses, lysed fetuses, number of resorption sites, and implantation sites. In the pregnant rats, no maternal toxicity was observed, despite presenting a significant anticipation of the offspring birth date. The rats belonging to the isoflavones 10 mg/kg and 100 mg/kg groups also gave birth to a smaller number of offspring. In female offspring, the parameters for presenting pelage, eyes opening, ears unfolding, and age for onset of puberty occurred early. At adult life, despite not observing any difference in the number of estruses, irregularities in estrous cycle including prolongation of the estrus phase in hours were observed in the group exposed to 10 mg/kg of isoflavones. These results indicate that isoflavones, despite presenting weak estrogenic activity, were able to interfere in sexual and bodily development, resulting in reproductive alterations. Extensive studies should be done, aiming to evaluate the possible effects of isoflavones in this critical development period.