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Recent mammalian studies have revealed that some endocrine disrupting chemicals (EDCs) can modify the epigenome by DNA methylation, histone modification or miRNAs interference, resulting in adverse transgenerational effects on subsequent generations (e.g. deformities, reproductive impairments and infertility), even though these offspring have never been exposed to EDCs throughout their whole life. In vitro studies carried out by our group showed that certain EDCs could modify the epigenome and potentially transmit the epigenetic changes through the human female and male germ lines. Using the marine medaka (Oryzias melastigma) as a fish model, this project set out to test the hypothesis that F0 exposed to environmental realistic concentration of certain EDCs can cause epigenetic alterations, leading to transgenerational reproductive impairment in both males and females in the subsequent generations (F1 to F3). Four EDCs commonly found in elevated concentrations in coastal waters of PRD and China were selected, and their transgenerational effects in association with Darwinian fitness traits (including gametogenesis, sperm number and motility, ovarian atresia, reproductive hormones and expression of related genes along the HPG axis, fecundity, onset of puberty, fertilization success, sex ratio, apoptosis and cell proliferation) are being studied. In parallel, high-throughput massively parallel sequencing will be used to reveal the epigenetic mechanism (i.e. miRNA profile, global and gene specific DNA methylation patterns) underlying the observed reproductive impairments. This research will enable us to coin a new class of pollutant with epigenetic and transgenerational effects, which is likely to attract global concern. The transgenerational effects revealed will compel a re-evaluation on the environmental and public health risks of these EDCs. Since endocrine and epigenetic regulations are highly conserved in vertebrates, our novel discoveries in this study will also shed light on epigenetic and transgenerational effects of epigenetic modifiers on higher vertebrates, including humans.
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