Embryonic atrazine exposure alters zebrafish and human miRNAs associated with angiogenesis, cancer, and neurodevelopment

Abstract

MicroRNAs (miRNAs) are short, single-stranded RNA that regulate post-transcriptional control of mRNA translation. Knowledge on the role of these critical regulators in toxicological responses in increasing, but is still limited. Atrazine is a herbicide used throughout the Midwestern US that is reported to frequently contaminate potable water supplies above the maximum contaminant level of 3 parts per billion. Atrazine is a suspected endocrine disrupting chemical and studies have begun to investigate the genetic mechanisms of toxicity; however, studies investigating epigenetic mechanisms are limited. In this study both zebrafish and human miRNAs were significantly altered in response to an embryonic atrazine exposure of 0.3, 3, or 30 ppb in zebrafish. Altered miRNAs are known to play a role in angiogenesis, cancer, or neuronal development, differentiation, and maturation. Targeted analysis of altered human miRNAs with genes previously identified to be altered by atrazine exposure revealed several targets linked to cell cycle and cell signaling. Further analysis of hsa-miRNA-126-3p, which had altered expression in all three atrazine treatments at 72 hpf, revealed alterations also occurred at 60 hpf in the 30 ppb treatment group. Results from this study indicate miRNA deregulation in zebrafish and human miRNAs following an embryonic atrazine exposure in zebrafish.

Atrazine exposure decreases the activity of DNMTs, global DNA methylation levels, and dnmt expression

“…49–50 In a previous study, we also first began to investigate epigenetic mechanisms behind the observed alterations in larvae and adult zebrafish by evaluating changes in microRNA (miRNA) expression following the same atrazine exposure regimen (i.e., an embryonic atrazine exposure at 0.3, 3, or 30 ppb throughout embryogenesis, 1–72 hpf). 47 Results from that study revealed alterations in miRNAs that were associated with angiogenesis, cancer, and neurodevelopment, but there are still questions on additional epigenetic mechanisms of atrazine toxicity including DNA methylation. 47 …”

“…20, 39–43 However, understanding the epigenetic alterations contributing to atrazine toxicity is still under investigation. 44–47 …”

Water Contaminated With the Herbicide Atrazine: Alteration of Cancer Associated Tumor Protein D52-like 1 (tpd52l1) Gene Using the Zebrafish Model

“…A least significant difference (LSD) post hoc test was performed if significance was met for the ANOVA test to establish when sets of data were different from each other, similar to other studies in our laboratory (Peterson et al, 2010;Wirbisky et al, 2015;Wirbisky et al, 2016). expression (p = 0.3040; see Figure 4C).…”

“…Moreover, the expression changes in tpd52l1 could impact how touch reflexes or blood circulation are affected at 36 hpf or impact the completion of morphogenesis for the 60 hpf alterations. In addition, from previous and ongoing studies, we know that atrazine also changes expression of other genes too and the interactions and relationships between the expression of tpd52l1 with these other gene targets needs further study (Weber et al, 2013;Wirbisky et al, 2015;Wirbisky et al, 2016). Overall, additional experiments need to be performed to better understand how exactly atrazine plays a mechanistic role in changing expression of the transcriptome and how these gene expression changes translate to adverse health effects.…”

“…Zebrafish were maintained and dosed with atrazine following previously established laboratory protocols (see Figure 2; Wirbisky et al, 2016). Adult zebrafish (Danio rerio) of the wild-type AB strain were housed on a 14-hour light-10-hour dark cycle in a Z-Mod alter anything throughout the body that is regulated by hormones.…”