The herbicide linuron inhibits cholesterol biosynthesis and induces cellular stress responses in brown trout.

Tamsyn M Uren Webster,Mandy H Perry,Eduarda M Santos

doi:10.1021/es505498u

Tamsyn M Uren Webster, Mandy H Perry + Show 1 more

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https://doi.org/10.1021/es505498u

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Abstract

The herbicide linuron is used worldwide, and has been detected in surface waters as well as in food and drinking water. Toxicological studies have reported that linuron acts as an antiandrogen in vitro and in vivo and disrupts mammalian male reproductive function. However, global mechanisms of linuron toxicity are poorly documented. We used RNA-seq to characterize the hepatic transcriptional response of mature male brown trout exposed for 4 days to 1.7, 15.3, and 225.9 μg/L linuron. We identified a striking decrease in the expression of transcripts encoding the majority of enzymes forming the cholesterol biosynthesis pathway. We also measured a very significant decrease in total hepatic cholesterol in fish exposed to 225.9 μg/L linuron and a negative correlation between total cholesterol and linuron treatment concentration. We hypothesize that inhibition of cholesterol biosynthesis may result from the disruption of androgen signaling by linuron. Additionally, there was increased expression of a number of transcripts involved in cellular stress responses, including cyp1a (up to 560-fold), molecular chaperones, and antioxidant enzymes. We found some evidence of similar patterns of transcriptional change in fish exposed to an environmentally relevant concentration of linuron, and further research should investigate the potential for adverse effects to occur following chronic environmental exposure.

Highlights

Linuron is a substituted phenylurea herbicide that disrupts photosynthesis by targeting protein D1, a central component of photosystem II, and inhibiting photodependent electron transport, leading to accumulation of reactive oxygen species (ROS) in plant cells.[1]
There were no significant differences between treatment groups in size and condition factor, HSI, or GSI of mature males, and we observed no alteration in the general health or behavior of the exposed fish during the experiment
Sequencing of the liver samples of fish exposed to linuron and associated controls generated a total of 137.9 million reads, averaging 9.2 million reads per sample, and 83.3% of these remapped against the assembled transcriptome

Summary

Introduction

Linuron is a substituted phenylurea herbicide that disrupts photosynthesis by targeting protein D1, a central component of photosystem II, and inhibiting photodependent electron transport, leading to accumulation of reactive oxygen species (ROS) in plant cells.[1]. Linuron is known to enter surface waters in agricultural runoff, in association with sediment, where it is moderately persistent.[2] Despite the widespread usage of this herbicide, measurements of surface water concentrations are very scarce but have been reported to occur in the nanogram to low microgram per liter range. Concentrations detected include 1.05 μg/L in a Canadian river within an agricultural catchment[3] and 4.42 μg/L in a Florida stream receiving agricultural runoff.[4] Modeling approaches have predicted peak concentrations of 31.3 μg/L in surface waters associated with application on a nearby carrot crop, highlighting the potential for short-term peaks in contamination.[2] Linuron has been detected in drinking water and in food residues.[5,6] The potential for environmental exposure to this chemical, raises concerns about the risk linuron may pose to both human and wildlife health

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