期刊
SCIENCE OF THE TOTAL ENVIRONMENT
卷 783, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.scitotenv.2021.147038
关键词
Whole transcriptome sequencing; Dibutyl phthalate; Circadian rhythm; Drosophila and human genetics; MCF10A cells
资金
- Formas
- Swedish Research Council
- CancerFonden
- IDUB 'Excellence InitiativeResearch University' program [DEC1/2020/IDUB/I.3.2]
The study shows that phthalates disrupt the circadian rhythm in both adult fruit flies and human cells, affecting the expression of genes related to circadian rhythm regulation and potentially promoting cell proliferation and migration ability.
People are constantly exposed to phthalates, due to their common use in the production of plastics, pharmaceuticals, cosmetics and skin care products. The ability of phthalates to disrupt endocrine signaling, leading to developmental, reproductive and metabolic defects, has been studied, yet how phthalates interfere with these biological functions is still unclear. To uncover DBP interacting molecular pathways, we raised Drosophila melanogaster on food containing dibutyl phthalate (DBP) at various concentrations. Whole transcriptome analysis of adult Drosophila reveals that DBP exposure throughout development disrupts the expression of genes central to circadian rhythm regulation, including increased expression of vrille (vri, human NFIL3), timeless (tim, human TIMELESS) and period (per, human PER3), with decreased expression of Pigment-dispersing factor (Pdf). DBP exposure also alters the expression of the evolutionarily conserved nuclear receptor Hormone receptor-like in 38 (Hr38, human NR4A2), which is known to regulate Pdf expression. Furthermore, behavioral assays determined that exposing Drosophila to DBP throughout development modifies the circadian rhythm of adults. Although DBP inhibits the expression of signaling systems regulating vision, including Rh5 and Rh6, two lightsensing G-protein coupled receptors involved in the daily resetting of circadian rhythm, it does not influence eye development. Circadian rhythm genes are well conserved from flies to humans; therefore, we tested the effect of DBP exposure on human breast cells (MCF10A) and demonstrate that, similar to the fruit fly model, this exposure disrupts circadian rhythm (BMAL1 expression) at doses that promote the proliferation and migration ability of MCF10A cells. Our results are the first to provide comprehensive evidence that DBP interferes with cir-cadian rhythm in both adult Drosophila , human cells, which may help to explain the broad physiological ac-tion of phthalates. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据