Ovarian Antral Follicles Metabolize Imidacloprid In Vitro

Vasiliki E Mourikes, Ramsés Santacruz-Márquez, Ashley Deviney, Mary J Laws, Alexander V Ulanov, Michael R La Frano, Jodi A Flaws

Research output: Contribution to journalArticlepeer-review


Neonicotinoid insecticides are synthetic nicotine derivatives that have high affinity for invertebrate nicotine receptors and low affinity for mammalian nicotine receptors. However, imidacloprid (IMI), the most commonly used neonicotinoid, can be bioactivated by the liver in mammals to desnitro-imidacloprid, an intermediate metabolite that effectively binds and activates mammalian receptors. However, it is not known if other tissues such as the ovaries can metabolize IMI. Thus, the present study tested the hypothesis that ovarian antral follicles metabolize and bioactivate IMI. Antral follicles were dissected from the ovaries of CD-1 mice and cultured in media containing dimethyl sulfoxide or IMI (0.2-200 µg/ml) for 48 and 96 h. Media were subjected to liquid chromatography-mass spectrometry for detection of phase I IMI metabolites. Follicles from the cultures were used for gene expression analysis of metabolic enzymes associated with IMI metabolism. All IMI metabolites were detected at 48 and 96 h. Oxidized IMI intermediates were detected in media from cultured follicles, but not environmental controls. Reduced IMI intermediates were detected in media from cultured follicles and the environmental controls. At 48 h, IMI did not affect expression of any metabolic enzymes compared with control. At 96 h, IMI induced Cyp2e1 and Cyp4f18 compared with control. These data indicate that mouse ovarian follicles metabolize IMI and that IMI induces ovarian Cyp expression over time.

Original languageEnglish (US)
Article numberkfad089
Pages (from-to)229-237
Number of pages9
JournalToxicological Sciences
Issue number2
Early online dateAug 26 2023
StatePublished - Dec 1 2023


  • antral follicles
  • neonicotinoids
  • imidacloprid
  • ovarian metabolism
  • reproductive toxicology
  • ovary

ASJC Scopus subject areas

  • Toxicology


Dive into the research topics of 'Ovarian Antral Follicles Metabolize Imidacloprid In Vitro'. Together they form a unique fingerprint.

Cite this