Abstract
Chemotherapy may result in ovarian atrophy, a depletion of the primordial follicle pool, diminished ovarian weight, cortical and stromal fibrosis. Imatinib mesylate is an anticancer agent that inhibits competitively several receptor tyrosine kinases (RTKs). RTKs play important roles in cell metabolism, proliferation, and apoptosis. In clinic, imatinib mesylate is also known as an anti-fibrotic medicine. In the present study, the impact of imatinib on the ovarian tissue was investigated by assessing ovarian tissue fibrosis in postnatal rat administered with or without imatinib for three days. Fibrosis in the ovarian tissue was determined by histology (Picrosirius and Masson's trichrome staining) and the protein expression of vimentin and alpha-smooth muscle actin (α-SMA). Furthermore, mRNA expression of Forkhead box transcription factor O1 and O3 (FOXO1 and FOXO3), which are markers of cell proliferation was quantified. A short-term exposure to imatinib showed to increase tissue fibrosis in ovaries. This was observed by Masson's trichrome staining. Exposure to imatinib led also to a down-regulation of vimentin protein expression and up-regulation mRNA expression of FOXO3. This may indicate a role of FOXO3 in ovarian tissue fibrosis in postnatal rat ovaries.
Original language | English |
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Pages (from-to) | 133-138 |
Number of pages | 6 |
Journal | Reproductive Biology |
Volume | 19 |
Issue number | 2 |
Early online date | 10 May 2019 |
DOIs | |
Publication status | Published - Jun 2019 |
Funding
This research was supported by grants from the Norwegian National Advisory Unit on Women’s Health, Oslo University Hospital, Norway and Faculty of Veterinary Medicine, IRAS, Utrecht University, Utrecht, the Netherlands .
Funders | Funder number |
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IRAS | |
Norwegian Institute of Public Health | |
Norwegian National Advisory Unit on Women's Health | |
Norwegian National Advisory Unit on Women’s Health | |
Oslo University Hospital | |
Universiteit Utrecht |
Keywords
- FOXO1
- FOXO3
- Imatinib
- Ovary
- Tissue fibrosis