A Three-generation Study on Male-mediated Developmental Toxicity in Mice Exposed to Bisphenol A and Bisphenol A–Irradiation Combination

Abstract

This chapter summarizes our long-term research on the effects of preconceptional exposure covering a full spermatogenesis cycle of pubescent or adult male mice to BPA or to a combination of BPA and irradiation on the male gametes and the development of two generations of their offspring. There were some differences in the response of male germ cells to bisphenol A exposure between adult and pubescent males. The harmful effect induced in the gametes of pubescent males by bisphenol A was more clear, suggesting the higher susceptibility of germ cells of adolescent mammals. Exposure of males to BPA alone or in combination with irradiation for a full cycle of spermatogenesis may cause heritable changes transferable to subsequent generations, which lead to unsuccessful fertilization or preimplantation losses as well as to death of pups after birth. Such exposure may also diminish the sperm quality of the males of the F1 generation leading to unsuccessful fertilization and induce obesity in the F1 offspring of exposed males. Combined treatment mainly intensified the harmful effect induced by BPA in male germ cells. Transgenerational effects on subsequent generations might involve genetic and epigenetic mechanisms.