Research Progress in Area 2 方向 ( 二 ) 課題進展 119 Abstract Endocrine Disrupting Chemicals (EDCs), despite occurring at very low concentration, can disturb hormonal balance, leading to reproductive impairment and malformation in animals. Some EDCs may further cause epigenetic changes, leading to adverse effects in subsequent generations. Emerging evidence suggest that ionizing radiation may also cause epigenetic changes. Using four different male and female reproductive cells as models, this study attempts to unravel the transcriptomic changes, and further inquire if there is any common epigenetic modification associated with reproductive impairments induced by radiation and different kinds of EDCs. The in vitro assays we successfully developed can serve as an effective tool to screen potential epigenetic modifiers for regulatory authorities worldwide. Research Activities and Progress • Unraveled and compared induced epigenetic effects in male and female reproductive cells through exposing two ovarian cancer cells (SKOV3 and COV434) and two testicular germ cells (GC-1 and TM4) to 9 EDCs with different chemical structure; • Completed most transcriptomic and bioinformatics analyses; • Published one paper in Frontier in Genetics (doi: 10.3389/fgene.2021.710143); • Presented two papers on two international conference. Key Findings • For the first time, we showed that radiation could alter the epigenome, leading to genderspeci c transgenerational reproductive impairments; • Comparative transcriptomic analysis showed that all the 9 EDCs tested could cause dysregulation of gene expression at different levels, with BP-3 causing the largest number of DEGs, followed by the plasticizers (i.e. DHP, DEHP, and NP). Notably, DEHP and NP shared a very similar effect gene dysregulation; • BP-3, NP, DEHP and EE2 altered the expression of gene clusters related to cell cycle, proliferation, and chromatin remodeling, which can lead to epigenetic modifications and transgenerational inheritance. BP-3 disturbed signaling pathways associated with reproductive functions, whereas EE2 altered telomere-related pathways; • Overall, this study highlighted the potential epigenetic modifications and mechanisms underlying transgenerational reproductive impairments caused by these EDCs and ionized radiation. Research Output Publication 1 Trained personnel 2 Development of a Suite of Novel in vitro Assays for Screening of Epigenetic Modifiers Prof. Rudolf Shiu Sun Wu The Education University of Hong Kong
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