Transgenerational and epigenetic effects of developmental exposure to atrazine on medaka (Oryzias latipes)

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Jacob Alexander Cleary (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Ramji Bhandari

Abstract: Exposure to environmental chemicals can cause epigenetic transgenerational inheritance of altered phenotypes. Chemicals such as the plasticizer bisphenol-A (BPA), the fungicidal vinclozolin, and the oral contraceptive component 17?-ethinylestradiol (EE2) induce epigenetic changes in various species. Each of these chemicals is an environmentally pervasive endocrine disrupting compound, as is the case with the abundantly used herbicide atrazine, whose endocrine disrupting mechanisms still remain unclear. Atrazine (ATZ) is presently one of the most abundantly used herbicides in the United States, and a common contaminant of natural water bodies and drinking waters in high-use areas. ATZ belongs to the triazine herbicides which specifically target photosynthetic tissues, yet ATZ can affect animal health. Fish exposed to ATZ and EE2 display dysregulation of reproductive processes, which include alterations to the hypothalamic-pituitary-gonadal (HPG) axis pathways. However, the potential for ATZ-induced transgenerational inheritance of reproductive dysfunction has not been investigated in fish. The transgenerational reproductive consequences of ATZ exposure have been explored in rats, but fish are among the species at greatest risk from ATZ exposure, therefore, I chose a model species to represent this environmentally relevant scenario. In the present study I analyzed the effects of ATZ and EE2 exposures during early development on transgenerational reproductive dysregulation in Japanese medaka (Oryzias latipes). F0 medaka were exposed to ATZ, EE2, and a solvent during the first twelve days of development with no exposure over the subsequent three generations. These early developmental exposures overlap with the critical windows of embryonic germ cell development, gonadogenesis, and sex determination when gonadal DNA methylation is being reprogrammed. Exposed males and females of the F0 treatment lineages were bred to produce the F1 generation, the F1 offspring were bred to produce the F2 generation, and the F2 offspring were bred to produce the F3 generation. Neither ATZ nor EE2 altered sperm parameters, gonadosomatic, or hepatosomatic indices in the treated F0 generation. However, the hepatosomatic index was reduced in F2 females derived from F0 fish treated with either ATZ or EE2. Hepatosomatic and gonadosomatic indices are ratios of liver and gonad weights to the total weight of the fish, which are cursory metrics for evaluating energetic and reproductive health. The fecundity of F0 and F2 fish was unaffected by exposure to ATZ or EE2; however, the fertilization rate was decreased among the F2 fish derived from the low ATZ and low EE2 treated F0 generation. Moreover, there were significant transgenerational differences in the expression of reproductive regulatory genes and genes required for DNA methylation. Genomic methylation patterns are catalyzed by DNA methyltransferase enzymes (dnmts) that regulate the heritable transcriptional activity of specific regions of DNA essential to development. Present results suggest that early life exposure to ATZ and EE2 cause no significant effects in the immediate generation, but that future generations of fish are at greater risk of reproductive dysfunction.

Additional Information

Language: English
Date: 2018
Epigenetics, HPG axis, Molecular Biology, Reproductive Disease, Transgenerational Inheritance
Molecular biology
Endocrine disrupting chemicals
Atrazine $x Physiological effect
Reproductive toxicology

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