Exposure of human fetal kidneys to mild analgesics interferes with early nephrogenesis

Sabrina Leverrier-Penna, Alain Michel, Laetitia L. Lecante, Nathalie Costet, Antonio Suglia, Christele Desdoits-Lethimonier, Hugoline Boulay, Roselyne Viel, Jonathan M. Chemouny, Emmanuelle Becker, Vincent Lavoue, Antoine D. Rolland, Nathalie Dejucq-Rainsford, Cecile Vigneau* (Corresponding Author), Séverine Mazaud Guittot* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Acetaminophen, aspirin, and ibuprofen are mild analgesics commonly used by pregnant women, the sole current recommendation being to avoid ibuprofen from the fifth month of gestation. The nephrotoxicity of these three analgesics is well documented in adults, as is their interference with prostaglandins biosynthesis. Here we investigated the effect of these analgesics on human first trimester kidneys ex vivo. We first evaluated prostaglandins biosynthesis functionality by performing a wide screening of prostaglandin expression patterns in first trimester human kidneys. We demonstrated that prostaglandins biosynthesis machinery is functional during early nephrogenesis. Human fetal kidney explants aged 7-12 developmental weeks were exposed ex vivo to ibuprofen, aspirin or acetaminophen for 7 days, and analyzed by histology, immunohistochemistry, and flow cytometry. This study has revealed that these analgesics induced a spectrum of abnormalities within early developing structures, ranging from cell death to a decline in differentiating glomeruli density. These results warrant caution for the use of these medicines during the first trimester of pregnancy.
Original languageEnglish
Article numbere21718
Number of pages19
JournalThe FASEB Journal
Volume35
Issue number7
Early online date9 Jun 2021
DOIs
Publication statusPublished - 1 Jul 2021

Keywords

  • acetaminophen
  • fetal kidney
  • nephrogenesis
  • NSAIDs
  • prostaglandins

Fingerprint

Dive into the research topics of 'Exposure of human fetal kidneys to mild analgesics interferes with early nephrogenesis'. Together they form a unique fingerprint.

Cite this