Chromatin modifiers: A new class of pollutants with potential epigenetic effects revealed by in vitro assays and transcriptomic analyses

Abstract

<p>A great variety of endocrine-disrupting chemicals (EDCs) have been used extensively and become widespread in the environment nowadays. Limited mammalian studies have shown that certain EDCs may target chromosome and epigenome of the germline, leading to adverse effects in subsequent generations, despite these progenies having never been exposed to the EDC before. However, the underlying mechanisms of chromosomal changes induced by these pollutants remain poorly known. Using the human ovarian granulosa tumor cell line COV434 as a model, we investigated and compared the transcriptomic changes induced by nine EDCs with diverse chemical structures (i.e. BDE-47, BPA, BP-3, DEHP, DHP, EE2, TCS, TDCPP and NP), to inquire if there is any common epigenetic modification associated with reproductive functions induced by these EDCs. Our results showed that COV434 cells were more responsive to BP-3, NP, DEHP and EE2, and more importantly, these four EDCs altered the expression of gene clusters related to DNA damage response, cell cycle, proliferation, and chromatin remodeling, which can potentially lead to epigenetic modifications and transgenerational inheritance. Furthermore, dysregulation of similar gene clusters was common in DEHP and NP treatments. Bioinformatics analysis further revealed that BP-3 disturbed signaling pathways associated with reproductive functions, whereas alterations in telomere-related pathways were highlighted upon EE2 exposure. Overall, this study highlighted chromatin modifications caused by a class of chemicals which that may potentially lead to epigenetic changes and transgenerational reproductive impairments.<br></p>