TY - JOUR
T1 - Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary
AU - Asadi-Azarbaijani, Babak
AU - Santos, Regiane R.
AU - Jahnukainen, Kirsi
AU - Braber, Saskia
AU - van Duursen, Majorie B.M.
AU - Toppari, Jorma
AU - Saugstad, Ola D.
AU - Nurmio, Mirja
AU - Oskam, Irma C.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Folliculogenesis
KW - Imatinib
KW - Oogenesis
KW - Ovary
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=85009347941&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85009347941&partnerID=8YFLogxK
U2 - 10.1016/j.repbio.2016.11.003
DO - 10.1016/j.repbio.2016.11.003
M3 - Article
C2 - 28040471
AN - SCOPUS:85009347941
VL - 17
SP - 25
EP - 33
JO - Reproductive Biology
JF - Reproductive Biology
SN - 1642-431X
IS - 1
ER -