Embryotoxic and Teratogenic Effects of the Combination of Bisphenol A and Genistein on In Vitro Cultured Postimplantation Rat Embryos

The potential teratogenic effects and fetal toxicity of environmental estrogenic endocrine disruptors have become a great concern in recent years, and they have yet to be fully characterized. In the present study, the teratogenic effects of bisphenol A (BPA) and genistein (GEN) on rat embryos during their critical period of organogenesis were investigated using a whole-embryo culture experiment. The combined exposure effects of BPA and GEN were explored using a 4 x 4 full factorial design. Both BPA and GEN produced concentration-dependent inhibition of embryonic development, beginning at 32.0 and 10.0 mu g/ml, respectively. Full factorial and isobologram analyses revealed a significant synergistic interaction between BPA and GEN for most end points (12 out of 20 tested), as indicated by the enhanced developmental toxicity of BPA after coexposure with different dose levels of GEN. In particular, serious malformations and a higher abnormal frequency of the central nervous system were induced by the combination of BPA and GEN. Our findings suggest that GEN may be embryotoxic and teratogenic to humans. BPA alone may not be a potential teratogen, but these two estrogenic chemicals have a synergistic effect on embryonic development when present together during the critical period of major organ formation. The current findings suggest that pregnant women should not take soy supplements, but more studies are necessary to provide a conclusive recommendation.