Maternal preconception PFOS exposure of Drosophila melanogaster alters reproductive capacity, development, morphology and nutrient regulation

Ju Hyeon Kim, Belinda Barbagallo, Kate Annunziato, Renalison Farias-Pereira, Jeffery J. Doherty, Jonghwa Lee, Jake Zina, Cole Tindal, Cailin McVey, Racheal Aresco, Megan Johnstone, Karilyn E. Sant, Alicia Timme-Laragy, Yeonhwa Park, John M. Clark

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Perfluorooctanesulfonic acid (PFOS) is a persistent synthetic surfactant widely detected in the environment. Developmental PFOS exposures are associated with low birth weight and chronic exposures increase risk for obesity and type 2 diabetes. As an obesogen, PFOS poses a major public health exposure risk and much remains to be understood about the critical windows of exposure and mechanisms impacted, especially during preconception. Here, we leverage evolutionarily conserved pathways and processes in the fruit fly Drosophila melanogaster (wild-type Canton-S and megalin-UAS RNAi transgenic fly lines) to investigate the window of maternal preconception exposure to PFOS on reproductive and developmental toxicity, and examine receptor (megalin)-mediated endocytosis of nutrients and PFOS into the oocyte as a potential mechanism. Preconception exposure to 2 ng PFOS/female resulted in an internal concentration of 0.081 ng/fly over two days post exposure, no mortality and reduced megalin transcription. The number of eggs laid 1–3 days post exposure was reduced and contained 0.018 ng PFOS/egg. Following heat shock, PFOS was significantly reduced in eggs from megalin-knockdown transgenic females. Cholesterol and triglycerides were increased in eggs laid immediately following PFOS exposure by non-heat shocked transgenic females whereas decreased cholesterol and increased protein levels were found in eggs laid by heat shocked transgenic females. Preconception exposure likewise increased cholesterol in early emerging wildtype F1 adults and also resulted in progeny with a substantial developmental delay, a reduction in adult weights, and altered transcription of Drosophila insulin-like peptide genes. These findings support an interaction between PFOS and megalin that interferes with normal nutrient transport during oocyte maturation and embryogenesis, which may be associated with later in life developmental delay and reduced weight.

Original languageEnglish
Article number112153
JournalFood and Chemical Toxicology
Volume151
DOIs
StatePublished - May 2021

Keywords

  • Development
  • Drosophila melanogaster
  • Nutrient regulation
  • Perfluorooctanesulfonic acid (PFOS)
  • Preconception exposure
  • Reproduction

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