期刊
REPRODUCTIVE BIOLOGY
卷 17, 期 1, 页码 25-33出版社
INST ANIMAL REPRODUCTION FOOD RESEARCH
DOI: 10.1016/j.repbio.2016.11.003
关键词
Imatinib; Folliculogenesis; Oogenesis; Rat; Ovary
资金
- Norwegian National Advisory Unit
- Oslo University Hospital, Norway
- Turku University
- The Academy of Finland
- The Sigrid juselius Foundation, Finland
Imatinib mesylate is an anti-cancer agent that competitively inhibits several receptor tyrosine kinases (RTKs). RTKs play important roles in the regulation of primordial follicle formation, the recruitment of primordial follicles into the pool of growing follicles and maturation of the follicles. In the present study, we investigated the effects of the tyrosine kinase inhibitor imatinib on primordial follicle assembly and early folliculogenesis in postnatal rats. Female Sprague-Dawley rats were treated with either imatinib (150 mg/kg) or placebo (water) on postnatal days 2-4. Bilateral ovariectomy was performed on postnatal day 2 and 5. Histology, immunohistochemistry, and mRNA analysis were performed. Imatinib treatment was associated with increased density of the multi-oocyte follicles (P < 0.01), oogonia (p < 0.01) and germline clusters (P < 0.05), decreased activation of primordial follicles, increased expression of c-Kit and AMH, and decreased protein expression of Kit-ligand and GDF9 when compared to age-matched controls. In conclusion, imatinib affects folliculogenesis in postnatal rat ovaries by delaying the cluster breakdown, follicular assembly and early activation of the primordial follicle pool. (C) 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Sp. z o.o. All rights reserved.
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