Early life stage trimethyltin exposure induces ADP-ribosylation factor expression and perturbs the vascular system in zebrafish.

TitleEarly life stage trimethyltin exposure induces ADP-ribosylation factor expression and perturbs the vascular system in zebrafish.
Publication TypeJournal Article
Year of Publication2012
AuthorsChen, J, Huang, C, Truong, L, La Du, J, Tilton, SC, Waters, KM, Lin, K, Tanguay, RL, Dong, Q
Date Published2012 Dec 16
KeywordsADP-Ribosylation Factors, Animals, Animals, Genetically Modified, Cardiovascular System, Embryo, Nonmammalian, Gene Expression Profiling, Gene Expression Regulation, Developmental, Lethal Dose 50, Microarray Analysis, Morpholinos, Reproducibility of Results, Trimethyltin Compounds, Zebrafish, Zebrafish Proteins

Trimethyltin chloride (TMT) is an organotin contaminant, widely detected in aqueous environments, posing potential human and environmental risks. In this study, we utilized the zebrafish model to investigate the impact of transient TMT exposure on developmental progression, angiogenesis, and cardiovascular development. Embryos were waterborne exposed to a wide TMT concentration range from 8 to 96 h post fertilization (hpf). The TMT concentration that led to mortality in 50% of the embryos (LC(50)) at 96 hpf was 8.2 μM; malformations in 50% of the embryos (EC(50)) was 2.8 μM. The predominant response observed in surviving embryos was pericardial edema. Additionally, using the Tg (fli1a: EGFP) y1 transgenic zebrafish line to non-invasively monitor vascular development, TMT exposure led to distinct disarrangements in the vascular system. The most susceptible developmental stage to TMT exposure was between 48 and 72 hpf. High density whole genome microarrays were used to identify the early transcriptional changes following TMT exposure from 48 to 60 hpf or 72 hpf. In total, 459 transcripts were differentially expressed at least 2-fold (P<0.05) by TMT compared to control. Using Ingenuity Pathway Analysis (IPA) tools, it was revealed that the transcripts misregulated by TMT exposure were clustered in numerous categories including metabolic and cardiovascular disease, cellular function, cell death, molecular transport, and physiological development. In situ localization of highly elevated transcripts revealed intense staining of ADP-ribosylation factors arf3 and arf5 in the head, trunk, and tail regions. When arf5 expression was blocked by morpholinos, the zebrafish did not display the prototypical TMT-induced vascular deficits, indicating that the induction of arf5 was necessary for TMT-induced vascular toxicity.

Alternate JournalToxicology
PubMed ID23000284
PubMed Central IDPMC3511642
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
P42ES 016465 / ES / NIEHS NIH HHS / United States