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Reprod Biol. 2019 May 9. pii: S1642-431X(18)30398-X. doi: 10.1016/j.repbio.2019.03.003. [Epub ahead of print]

Imatinib mesylate does not counteract ovarian tissue fibrosis in postnatal rat ovary.

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VID Specialized University, Faculty of Health studies, Oslo, Norway. Electronic address:
Faculty of Veterinary Medicine, IRAS, Utrecht University, Utrecht, the Netherlands.
Department of Environment and Health, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
New Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Women's and Children´s Health, NORDFERTIL Research Lab, Stockholm, Sweden.
Laboratory of Wild Animal Biology and Medicine, Federal University of Pará, Castanhal, Pará, Brazil; Schothorst Feed Research, Lelystad, the Netherlands.
The production animal experimental research centre (SHF), Norwegian University of Life Sciences, Oslo, Norway.


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.


FOXO1; FOXO3; Imatinib; Ovary; Tissue fibrosis

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