Pressing environmental and public health concerns in the coming decades: Chemicals causing epigenetic alterations and transgenerational effects

Rapid growing evidence in the last decade showed that certain stress and chemicals in our environment and food may cause epigenetic alterations, including changes in DNA methylation patterns, histone modification and microRNA profile in animals. Laboratory evidence further showed that some of these epigenetic alterations may potentially trigger cancer, obesity, diabetes and reproductive impairments in subsequent generations (F1-F3), despite the latter have never been exposed to these chemicals before. For the first time, we show that F0 of fish exposed to hypoxia can lead to reproductive impairments in F1 and F2, despite these progenies having never been exposed to hypoxia. We further provide evidence that the observed transgenerational reproductive impairments are associated with changes in methylation pattern of specific genes in sperms of both F0 and F2, coupled with transcriptomic and proteomic alterations related to impair spermatogenesis. Because the genes regulating spermatogenesis and epigenetic modifications are highly conserved among vertebrates, these results may also shed light on the potential transgenerational effects of hypoxia on other vertebrates, including humans. It is argued that chemicals that can cause epigenetic changes and transgenerational effects would pose a significant and long lasting threat to natural and human populations, and should therefore receive major attention in the coming decades. To this end, we have developed: (a) two in vitro systems (using testicular and ovarian primary cell cultures of marine medaka) for screening chemicals with epigenetic disrupting potential; and (b) two in vivo systems (using growth, reproduction and development of zebrafish and Daphnia) for screening chemicals with transgenerational effects of environmental contaminants. We also propose to use the QSAR approach to analyze the data with a view to predict the epigenetic alternation and transgenerational potential of chemicals in the future.