Long-term imatinib diminishes ovarian reserve and impacts embryo quality.
Embryo
Fertility preservation
Imatinib
Oocyte
Ovary
Journal
Journal of assisted reproduction and genetics
ISSN: 1573-7330
Titre abrégé: J Assist Reprod Genet
Pays: Netherlands
ID NLM: 9206495
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
21
01
2020
accepted:
08
04
2020
pubmed:
7
5
2020
medline:
4
2
2021
entrez:
7
5
2020
Statut:
ppublish
Résumé
Tyrosine kinase inhibitors (TKIs) such as imatinib are commonly used chemotherapeutics, but the effects of long-term treatments on reproductive outlook for cancer survivors are unknown. The purpose of this study was to examine the effects of long-term imatinib treatments on follicle development and embryo quality. Since prospective studies are not possible in healthy humans, we have incorporated a commonly used mouse model. Adult female mice were treated with daily IP injections of imatinib for 4-6 weeks. Liquid chromatography-mass spectrometry was used to measure imatinib in serum and ovarian tissues. At the end of treatments, females were superovulated and mated to yield fertilized embryos. Oocytes and embryos were collected from oviducts, assessed for development by microscopy, and fertilized embryos were cultured in vitro. Blastocysts were fixed and stained for differential cell counts. Long-term imatinib treatments caused a shift in follicle development, with imatinib-treated females having fewer primordial follicles, but an increase in primary and secondary follicles (P < 0.05). There was no effect on ovulation or fertilization rates. However, blastocysts from imatinib-treated females had fewer total cells (P < 0.05) and a significant shift from inner cell mass to increased trophectoderm cells. This pilot study indicates that long-term TKI treatments may have significant impact on ovarian reserve and embryo developmental capacity. More studies are needed in other model systems to determine the long-term impact of TKIs in patients. Knowing the potential effects of chemotherapeutics on reproductive outlook is critical for quality of life and more research is needed.
Identifiants
pubmed: 32372302
doi: 10.1007/s10815-020-01778-7
pii: 10.1007/s10815-020-01778-7
pmc: PMC7311628
doi:
Substances chimiques
Imatinib Mesylate
8A1O1M485B
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1459-1466Subventions
Organisme : American Cancer Society
ID : IRG-58-007-54
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