Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary

Babak Asadi-Azarbaijani; Regiane R. Santos; Kirsi Jahnukainen; Saskia Braber; Majorie B M van Duursen; Jorma Toppari; Ola D Saugstad; Mirja Nurmio; Irma C Oskam

doi:10.1016/j.repbio.2016.11.003

Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary

Babak Asadi-Azarbaijani, Regiane R. Santos, Kirsi Jahnukainen, Saskia Braber, Majorie B M van Duursen, Jorma Toppari, Ola D Saugstad, Mirja Nurmio, Irma C Oskam

Pharmacology

Women and Children's Division, Oslo University Hospital, Rikshospitalet, Oslo, Norway; University of Oslo, Oslo, Norway. Electronic address: [email protected].
Faculty of Veterinary Medicine, IRAS, Utrecht University, Utrecht, The Netherlands; Laboratory of Wild Animal Biology and Medicine, Federal University of Pará, Castanhal, Pará, Brazil.
Department of Pediatrics, Helsinki University Central Hospital, Helsinki, Finland; Department of Women's and Childreńs Health, Karolinska Institute and University Hospital, Stockholm, Sweden.
Institute of Biomedicine, Department of Physiology, University of Turku, and Department of Pediatrics, Turku University Hospital, Turku, Finland.
University of Oslo, Oslo, Norway; The Pediatric Research Institute, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Norwegian University of Life Sciences, Oslo, Norway.

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 (150mg/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.

Original language	English
Pages (from-to)	25-33
Number of pages	9
Journal	Reproductive Biology
Volume	17
Issue number	1
DOIs	https://doi.org/10.1016/j.repbio.2016.11.003
Publication status	Published - Mar 2017

Keywords

Animals
Animals, Newborn
Anti-Mullerian Hormone
Antineoplastic Agents
Apoptosis
Biomarkers
Female
Gene Expression Regulation, Developmental
Growth Differentiation Factor 9
Imatinib Mesylate
Immunohistochemistry
Oogenesis
Oogonia
Oogonial Stem Cells
Ovarian Follicle
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-kit
RNA, Messenger
Rats, Sprague-Dawley
Stem Cell Factor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.repbio.2016.11.003

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Asadi-Azarbaijani, B., Santos, R. R., Jahnukainen, K., Braber, S., van Duursen, M. B. M., Toppari, J., Saugstad, O. D., Nurmio, M., & Oskam, I. C. (2017). Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary. Reproductive Biology, 17(1), 25-33. https://doi.org/10.1016/j.repbio.2016.11.003

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title = "Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary",

abstract = "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 (150mg/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.",

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author = "Babak Asadi-Azarbaijani and Santos, {Regiane R.} and Kirsi Jahnukainen and Saskia Braber and {van Duursen}, {Majorie B M} and Jorma Toppari and Saugstad, {Ola D} and Mirja Nurmio and Oskam, {Irma C}",

note = "Copyright {\textcopyright} 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.",

year = "2017",

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doi = "10.1016/j.repbio.2016.11.003",

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journal = "Reproductive Biology",

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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

N1 - Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

PY - 2017/3

Y1 - 2017/3

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 (150mg/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 (150mg/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 - Animals

KW - Animals, Newborn

KW - Anti-Mullerian Hormone

KW - Antineoplastic Agents

KW - Apoptosis

KW - Biomarkers

KW - Female

KW - Gene Expression Regulation, Developmental

KW - Growth Differentiation Factor 9

KW - Imatinib Mesylate

KW - Immunohistochemistry

KW - Oogenesis

KW - Oogonia

KW - Oogonial Stem Cells

KW - Ovarian Follicle

KW - Protein Kinase Inhibitors

KW - Proto-Oncogene Proteins c-kit

KW - RNA, Messenger

KW - Rats, Sprague-Dawley

KW - Stem Cell Factor

U2 - 10.1016/j.repbio.2016.11.003

DO - 10.1016/j.repbio.2016.11.003

M3 - Article

C2 - 28040471

SN - 1642-431X

VL - 17

SP - 25

EP - 33

JO - Reproductive Biology

JF - Reproductive Biology

IS - 1

ER -

Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary

Abstract

Keywords

UN SDGs

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