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Ovarian Tissue Culture to Visualize Phenomena in Mouse Ovary
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Imatinib mesylate does not counteract ovarian tissue fibrosis in postnatal rat ovary

Babak Asadi-Azarbaijani1, Saskia Braber2, Majorie van Duursen3

  • 1VID Specialized University, Faculty of Health studies, Oslo, Norway.

Reproductive Biology
|May 14, 2019
PubMed

Insights

Imatinib mesylate, an anticancer drug, unexpectedly increased ovarian fibrosis in young rats. This study suggests a potential role for FOXO3 in this fibrotic response, highlighting a concerning side effect of this medication.

Area of Science:

  • Reproductive biology
  • Pharmacology
  • Oncology

Background:

  • Chemotherapy can cause ovarian atrophy and fibrosis.
  • Imatinib mesylate is an anticancer drug that inhibits receptor tyrosine kinases (RTKs) and is known for anti-fibrotic properties.

Purpose of the Study:

  • To investigate the impact of imatinib mesylate on ovarian tissue fibrosis in postnatal rats.
  • To assess the effects of short-term imatinib exposure on ovarian histology and molecular markers.

Main Methods:

  • Postnatal rats were administered imatinib or a placebo for three days.
  • Ovarian tissue fibrosis was evaluated using Masson's trichrome and Picrosirius staining.
  • Protein expression of vimentin and alpha-smooth muscle actin (α-SMA) was measured.
  • mRNA expression of Forkhead box transcription factor O1 and O3 (FOXO1 and FOXO3) was quantified.

Main Results:

  • Short-term imatinib exposure led to increased ovarian tissue fibrosis, confirmed by Masson's trichrome staining.
  • Imatinib treatment resulted in decreased vimentin protein expression.
  • A significant up-regulation of FOXO3 mRNA expression was observed.

Conclusions:

  • Imatinib mesylate can induce fibrosis in the ovaries of young rats, contrary to its known anti-fibrotic effects in other contexts.
  • The up-regulation of FOXO3 suggests its potential involvement in imatinib-induced ovarian fibrosis.
Keywords:
FOXO1FOXO3ImatinibOvaryTissue fibrosis

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