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.
We thank the entire staff of the Obstetrics and Gynecology Department of the Rennes Sud Hospital (Rennes, France), along with the participating women, without whom this study would have been impossible. We thank Pauline Le Faouder from the MetaToul-Lipidomique core facility (I2MC, Inserm 1048, Toulouse, France), MetaboHUB-ANR-11-INBS-0010 for prostaglandin measurements. Thanks to the staff at the Biosit histopathology platform (Biogenouest, Université de Rennes 1, Rennes, France). We are grateful to Isabelle Coiffec for help with organ collection, and to Juliana Berland for American editing. This study was funded by Inserm, University of Rennes 1, EHESP—School of Public Health. SLP was a recipient of a stipend from the Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM; HAP-2014-073), LL from the Agence Nationale de la Recherche (ANR-15-CE34-0001-01) and AM from The French Society of Nephrology.
- fetal kidney