Developmental phenotypic and transcriptomic effects of exposure to nanomolar levels of metformin in zebrafish

Environ Toxicol Pharmacol. 2021 Oct:87:103716. doi: 10.1016/j.etap.2021.103716. Epub 2021 Jul 24.

Abstract

Metformin is found in the majority of lakes and streams in the United States, leading to widespread environmental exposure. Results of the present study indicate that extended duration metformin exposure at critical developmental periods leads to decreased survival rates in zebrafish (danio rerio), an NIH approved human model. Significant abnormalities are seen with extended duration metformin exposure from 4 h post fertilization up to 5 days post fertilization, although short term metformin exposure for 24 h at 4-5 days post fertilization did not lead to any significant abnormalities. Both extended and short term duration did however have an impact on locomotor activity of zebrafish, and several genes involved in neurological and cardiovascular development were differentially expressed after exposure to metformin. The changes seen in behavior, gene expression and morphological abnormalities caused by metformin exposure should be examined further in future studies in order to assess their potential human health implications as metformin prescriptions continue to increase worldwide.

Keywords: Aquatic environment; Danio rerio; Environmental toxicity; Ground water chemicals; Metformin; Zebrafish.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Bone and Bones / abnormalities
  • Edema, Cardiac
  • Embryo, Nonmammalian / abnormalities
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / physiology
  • Embryonic Development / drug effects*
  • Female
  • Locomotion / drug effects
  • Male
  • Metformin / toxicity*
  • Phenotype
  • Teratogens / toxicity*
  • Transcriptome / drug effects*
  • Water Pollutants, Chemical / toxicity*
  • Zebrafish* / abnormalities
  • Zebrafish* / genetics
  • Zebrafish* / physiology

Substances

  • Teratogens
  • Water Pollutants, Chemical
  • Metformin