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

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. Animal(s) Six- and 8-week-old C57Bl/6 female mice. Intervention(s) 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 dimethyl sulfoxide (DMSO; vehicle control). Main Outcome Measure(s) Follicle counts, microvessel density, cellular response to DNA damage, and litter production. Result(s) G-CSF ± SCF increased microvessel density and decreased follicle loss in CTx-treated female mice compared with 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. Conclusion(s) 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 GnRH analogue treatments.

Granulocyte colony-stimulating factor prevents loss of spermatogenesis after sterilizing busulfan chemotherapy

“…A previous mouse study revealed that G-CSF promoted retention of ovarian reserve in females treated with alkylating chemotherapy (55). To examine the possibility of a similar fertility-preserving G-CSF effect in males, we performed two separate experiments using 5 week-old C57BL/6 mice in conjunction with sterilizing busulfan treatment.…”

“…Since a previous study in female mouse identified a fertility-preserving effect of G-CSF in animals treated with alkylating chemotherapy (55), we tested whether a similar phenomenon might occur in males. Our first experiment demonstrated that mouse spermatogenesis can be protected from busulfan chemotherapy by treatment with the cytokine granulocyte colony-stimulating factor (G-CSF).…”

The effect of DHEA on apoptosis and cohesin levels in oocytes in aged mice

“…This effect was presumably achieved by inhibiting follicular atresia (35). Anti-γH 2 AX staining indicated that atretic follicles were rescued by suppressing DNA double-strand breaks (36). DNA double-strand breaks play a major role in the ovarian aging process and the age-related decline in fertility.…”

“…After incubation with the primary antibodies overnight, the slides were washed with PBS three times and then incubated with biotinylated-conjugated secondary antibody (Zymed Laboratories-Invitrogen, San Francisco, CA, USA) for 15 minutes at room temperature. Follicles were considered γH 2 AX-positive if the oocyte or > 50% of GCs were positive (36). Images were obtained using the Olympus Scanner.…”

Fertility preservation and reproductive health in the pediatric, adolescent, and young adult female cancer patient

“…Likewise, granulocyte colony-stimulating factor has been shown in mice to delay primary ovarian insufficiency POI after cyclophosphamide treatment [48,56,57]. Further research is warranted in this area.…”