Lyche Jan L, Grześ Irena M, Karlsson Camilla, Nourizadeh-Lillabadi Rasoul, Aleström Peter, Ropstad Erik
a Department of Food Safety and Infection Biology , Norwegian University of Life Science , Oslo , Norway.
b Institute of Environmental Sciences , Jagiellonian Uniwersity , Kraków , Poland.
J Toxicol Environ Health A. 2016;79(13-15):602-11. doi: 10.1080/15287394.2016.1171991.
Apoptosis is an integral element of development that may also be initiated by environmental contaminants. The aim of the present study was to assess potential changes in the regulation of apoptotic genes in zebrafish embryos following parental exposure to two natural mixtures of persistent organic pollutants (POP). The mixture from Lake Mjøsa contained exceptionally high concentrations of polybrominated diphenyl ethers (PBDE), as well as relatively high levels of polychlorinated biphenyls (PCB) and dichlorodiphenyltrichloroethane (DDT). The mixture from Lake Losna contained background concentrations of POP. Genes involved in the apoptotic machinery were screened for their expression profile at four time points during embryonic development. Thirteen and 15 genes involved in apoptosis were found to be significantly upregulated in the high-exposure and background exposure groups, respectively, compared with controls. Modulation of apoptotic genes was restricted only to the first time point, which corresponds with the blastula stage. Although there were substantial differences in POP concentrations between mixtures, genes underlying the apoptosis process showed almost similar responses to the two mixtures. In both exposure groups the main executors of apoptosis p53, casp 2, casp 6, cassp 8, and BAX displayed upregulation compared to controls, suggesting that these POP induce apoptosis via a p53-dependent mechanism. Upregulation of genes that play a critical role in apoptosis suggests that disturbance of normal apoptotic signaling during gametogenesis and embryogenesis may be one of the central mechanisms involved in adverse reproductive effects produced by POP in zebrafish.
细胞凋亡是发育过程中不可或缺的一部分，环境污染物也可能引发细胞凋亡。本研究的目的是评估亲代暴露于两种持久性有机污染物（POP）天然混合物后，斑马鱼胚胎中凋亡基因调控的潜在变化。米约萨湖的混合物含有极高浓度的多溴二苯醚（PBDE），以及相对较高水平的多氯联苯（PCB）和二氯二苯三氯乙烷（DDT）。洛斯纳湖的混合物含有POP的背景浓度。在胚胎发育的四个时间点筛选参与凋亡机制的基因的表达谱。与对照组相比，在高暴露组和背景暴露组中分别发现13个和15个参与凋亡的基因显著上调。凋亡基因的调节仅局限于第一个时间点，该时间点与囊胚期相对应。尽管两种混合物中POP浓度存在显著差异，但凋亡过程的相关基因对两种混合物的反应几乎相似。在两个暴露组中，凋亡的主要执行者p53、casp 2、casp 6、casp 8和BAX与对照组相比均上调，表明这些POP通过p53依赖性机制诱导细胞凋亡。在凋亡中起关键作用的基因上调表明，配子发生和胚胎发生过程中正常凋亡信号的紊乱可能是POP对斑马鱼产生不良生殖影响的核心机制之一。
