Embryonic atrazine exposure and later in life behavioral and brain transcriptomic, epigenetic, and pathological alterations in adult male zebrafish

• Published in: Cell biology and toxicology 2021-06, Vol.37 (3), p.421-439
• Main Authors: Horzmann, Katharine A., Lin, Li F., Taslakjian, Boghos, Yuan, Chongli, Freeman, Jennifer L.
• Format: Article
• Language: English
• Subjects: Animals; Atrazine; Atrazine - adverse effects; Biochemistry; Biomedical and Life Sciences; Body length; Body weight; Brain; Brain - drug effects; Brain - pathology; Cancer; Cell Biology; Contaminants; Danio rerio; DNA methylation; Embryogenesis; Embryonic Development - drug effects; Embryonic growth stage; Embryos; Endocrine disruptors; Endocrine Disruptors - adverse effects; Environmental protection; Epigenesis, Genetic - drug effects; Epigenetics; Evaluation; Exposure; Fertilization; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation, Developmental - drug effects; Genomes; Herbicides; Humans; Larva - drug effects; Larva - genetics; Larva - growth & development; Life Sciences; Males; Methylation; Neurotoxicity; Original Article; Parameter identification; Pesticides; Pesticides - adverse effects; Pharmacology/Toxicology; Reproductive system; Transcriptome - drug effects; Transcriptome - genetics; Transcriptomes; Water Pollutants, Chemical - adverse effects; Water pollution; Zebrafish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - growth & development
• ISSN: 0742-2091; 1573-6822
• DOI: 10.1007/s10565-020-09548-y

Atrazine (ATZ), a commonly used pesticide linked to endocrine disruption, cancer, and altered neurochemistry, frequently contaminates water sources at levels above the US Environmental Protection Agency’s 3 parts per billion (ppb; μg/L) maximum contaminant level. Adult male zebrafish behavior, brain transcriptome, brain methylation status, and neuropathology were examined to test the hypothesis that embryonic ATZ exposure causes delayed neurotoxicity, according to the developmental origins of health and disease paradigm. Zebrafish ( Danio rerio ) embryos were exposed to 0 ppb, 0.3 ppb, 3 ppb, or 30 ppb ATZ during embryogenesis (1–72 h post fertilization (hpf)), then rinsed and raised to maturity. At 9 months post fertilization (mpf), males had decreased locomotor parameters during a battery of behavioral tests. Transcriptomic analysis identified altered gene expression in organismal development, cancer, and nervous and reproductive system development and function pathways and networks. The brain was evaluated histopathologically for morphometric differences, and decreased numbers of cells were identified in raphe populations. Global methylation levels were evaluated at 12 mpf, and the body length, body weight, and brain weight were measured at 14 mpf to evaluate effects of ATZ on mature brain size. No significant difference in genome methylation or brain size was observed. The results demonstrate that developmental exposure to ATZ does affect neurodevelopment and neural function in adult male zebrafish and raises concern for possible health effects in humans due to ATZ’s environmental presence and persistence. Graphical abstract