Tris(4-chlorophenyl)methane and tris(4-chlorophenyl)methanol disrupt pancreatic organogenesis and gene expression in zebrafish embryos.
Tris(4-chlorophenyl)methane and tris(4-chlorophenyl)methanol disrupt pancreatic organogenesis and gene expression in zebrafish embryos.
复制标题
DOI：
10.1002/bdr2.2132
复制
发表时间：
2023-03-01
影响因子：
2.1
通讯作者：
Sant, Karilyn E.
中科院分区：
文献类型：
--
作者：
Wilson, Peyton W.;Cho, Christine;Allsing, Nicholas;Khanum, Saleha;Bose, Pria;Grubschmidt, Ava;Sant, Karilyn E.
三（4-氯苯基）甲烷（TCPM）和三（4-氯苯基）甲醇（TCPMOH）是有机氯农药滴滴涕（DDT）生产过程中产生的环境污染物。TCPM和TCPMOH具有持久性，在环境中具有生物累积性，并在人类母乳和脂肪组织中检测到。由于类似的有机氯的毒性，我们确定了对斑马鱼胰腺生长和基因表达的影响，发育暴露。从受精后24小时（hpf）开始，将斑马鱼胚胎暴露于50 nM TCPM或TCPMOH，并每天更新暴露。在96 hpf时，使用显微镜分别在Tg（ptf 1a：：GFP）和Tg（胰岛素：：GFP）胚胎中直接观察胰腺生长和胰岛面积。在100 hpf下用RNA测序评估基因表达。与对照组相比，暴露于50 nM TCPMOH的胚胎中胰岛和总胰腺面积分别减少了20.8%和13%。TCPM未诱导发育中的胰腺发生显著的形态学变化，表明TCPMOH而非TCPM损害胰腺发育，尽管分子反应相似。TCPM和TCPMOH的转录组反应相关（R2=0.903），通路分析发现包括视黄醇代谢，昼夜节律和类固醇生物合成的过程下调。总的来说，我们的数据表明，TCPM和TCPMOH可能对胚胎生长和发育有害。
Tris(4-chlorophenyl) methane (TCPM) and tris(4-chlorophenyl)methanol (TCPMOH) are anthropogenic environmental contaminants believed to be manufacturing byproducts of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) due to environmental co-occurrence. TCPM and TCPMOH are persistent, bioaccumulate in the environment, and are detected in human breast milk and adipose tissues. Due to the toxicity of similar organochlorines, we determined impacts on zebrafish pancreatic growth and gene expression following developmental exposures. Zebrafish embryos were exposed to 50 nM TCPM or TCPMOH beginning at 24 hours post fertilization (hpf) and exposures were refreshed daily. At 96 hpf, pancreatic growth and islet area were directly visualized in Tg(ptf1a::GFP) and Tg(insulin::GFP) embryos, respectively, using microscopy. Gene expression was assessed at 100 hpf with RNA sequencing. Islet and total pancreas area were reduced by 20.8% and 13% in embryos exposed to 50 nM TCPMOH compared to controls. TCPM did not induce significant morphological changes to the developing pancreas, indicating TCPMOH, but not TCPM, impairs pancreatic development despite similarity in molecular responses. Transcriptomic responses to TCPM and TCPMOH were correlated (R2=0.903), and pathway analysis found downregulation of processes including retinol metabolism, circadian rhythm, and steroid biosynthesis. Overall, our data suggest that TCPM and TCPMOH may be hazardous to embryonic growth and development.
登录
查看更多内容
影响因子：
10.4
作者：
通讯作者：
--
影响因子：
8.8
作者：
Foster, WG;Desaulniers, D;Chu, I
通讯作者：
Chu, I
影响因子：
11.4
作者：
JARMAN, WM;SIMON, M;RISEBROUGH, RW
通讯作者：
RISEBROUGH, RW
影响因子：
3.2
作者：
Jeon, Jongmin;Correa-Medina, Mayrin;Diez, Juan A.
通讯作者：
Diez, Juan A.
影响因子：
2.7
作者：
diIorio, PJ;Moss, JB;Moss, LG
通讯作者：
Moss, LG