Granulocyte colony stimulating factor with or without stem cell factor extends time to premature ovarian insufficiency in female mice treated with alkylating chemotherapy

Capsule:
Treatment of mice with G-CSF with or without SCF protects ovarian follicle pool and extends time to premature ovarian insufficiency in mice treated with alkylating chemotherapy.

Authors:
Malgorzata E. Skaznik-Wikiel, M.D., Megan M. McGuire, B.S., Meena Sukhwani, Ph.D., Julia Donohue, B.S., Tianjiao Chu, Ph.D., Thomas C. Krivak, M.D., Aleksandar Rajkovic, M.D., Ph.D., Kyle E. Orwig, Ph.D.

Volume 99, Issue 7, Pages 2045-2054.e3, June 2013

Abstract:

Objective:
To examine gonadal protective properties of granulocyte colony stimulating factor (G-CSF) alone or in combination with stem cell factor (SCF) in female mice treated with high-dose alkylating chemotherapy.

Design:
Experimental laboratory animal study.

Setting:
Tertiary care academic hospital and research institute.

Animals:
Six- and 8-week-old C57Bl/6 female mice.

Interventions:
Adult female mice were treated with 1) cyclophosphamide and busulfan (CTx), 2) CTx + G-CSF/SCF, 3) CTx + G-CSF, or 4) normal saline and DMSO (vehicle control).

Main outcome measures:
Follicle counts, microvessel density, cellular response to DNA damage, and litter production.

Results:
G-CSF ± SCF increased microvessel density and decreased follicle loss in CTx-treated female mice compared to CTx-only treated female mice. Mice administered CTx alone exhibited premature ovarian insufficiency, with only 28% of mice producing two litters. However, 100% of mice receiving CTx with G-CSF + SCF, and 80% of mice receiving CTx + G-CSF alone produced at least three litters and 20% of mice in each group produced five litters.

Conclusions:
Treatment of mice with G-CSF decreases chemotherapy-induced ovarian follicle loss and extends time to premature ovarian insufficiency in female mice. Further studies are needed to validate these preclinical results in humans and compare efficacy with the established GnRHa treatments.

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