ESA-SRB-AOTA 2019

Determining the impact of environmental toxins on the germline epigenome and offspring development (#681)

Elyse OK Swindells 1 , Jessica M Stringer 1 , Karla J Hutt 1
  1. Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia

Atrazine is one of the most widely used pesticides worldwide, with annual use exceeding 35,000 tonnes in the USA (1) and 3,000 tonnes in Australia (2). Atrazine is a common ground and surface water contaminant, with up to 1.65ng/ml detected in southeast Australia(3), and up to 7.6ng/ml in Queensland (4). Accumulating evidence suggests atrazine may act as an endocrine disruptor, interfering with reproductive health and function (5-7). Additionally, atrazine is shown to alter male germline epigenetic programming (8, 9). These studies, however, utilise short term, high dose exposures, focusing on male health and reproductive outcomes. Comprehensive analyses of environmentally-relevant doses and of chronic, multi-generational exposure on ovarian function and female fertility are lacking.

We aim to characterise the impacts of atrazine on female germline development, epigenetic programming, DNA damage, and fertility, using low (0.02ng/ml), medium (0.02ug/ml), and high (0.02mg/ml) exposure levels. To characterise embryonic exposure, pregnant dams will receive atrazine via drinking water from E9.5-17.5, encompassing sex-specific epigenetic reprogramming of the embryonic germline. Additionally, to assess direct insult to the ovaries, we will supplement ovary cultures with atrazine. To characterise adult exposure, female mice will receive atrazine for three weeks, a period encompassing follicle growth from activation to pre-ovulatory stage. Finally, to assess long term atrazine exposure, we will supplement drinking water of female mice for at least 3 generations.

This study will generate data to guide atrazine legislation and regulation. Elucidating the impacts of exposure may aid fertility management not only in humans, but also in agricultural cattle and native wildlife breeding programs.

  1. Agency UEP. Decision Documents for Atrazine. 2006.
  2. Radcliffe JC. Pesticide use in Australia. Victoria, Australia: Aust Acad of Tech Sci Eng.; 2002
  3. Allinson G, Allinson M, Bui A, Zhang P, Croatto G, Wightwick A, et al. Pesticide and trace metals in surface waters and sediments of rivers entering the Corner Inlet Marine National Park, Victoria, Australia. Environmental science and pollution research international. 2016;23(6):5881-91.
  4. Magnusson M, Heimann K, Ridd M, Negri AP. Pesticide contamination and phytotoxicity of sediment interstitial water to tropical benthic microalgae. Water Research. 2013;47(14):5211-21.
  5. Cooper RL, Laws SC, Das PC, Narotsky MG, Goldman JM, Lee Tyrey E, et al. Atrazine and reproductive function: mode and mechanism of action studies. Birth defects research Part B, Developmental and reproductive toxicology. 2007;80(2):98-112.
  6. Rayner JL, Wood C, Fenton SE. Exposure parameters necessary for delayed puberty and mammary gland development in Long–Evans rats exposed in utero to atrazine. Toxicology and Applied Pharmacology. 2004;195(1):23-34.
  7. Hayes TB, Khoury V, Narayan A, Nazir M, Park A, Brown T, et al. Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis). Proceedings of the National Academy of Sciences of the United States of America. 2010;107(10):4612-7.
  8. Gely-Pernot A, Saci S, Kernanec PY, Hao C, Giton F, Kervarrec C, et al. Embryonic exposure to the widely-used herbicide atrazine disrupts meiosis and normal follicle formation in female mice. Scientific reports. 2017;7(1):3526.
  9. Hao C, Gely-Pernot A, Kervarrec C, Boudjema M, Becker E, Khil P, et al. Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice. Nucleic acids research. 2016;44(20):9784-802.