Granulocyte colony-stimulating factor (G-CSF) promotes spermatogenic regeneration from surviving spermatogonia after high-dose alkylating chemotherapy

粒细胞集落刺激因子(G-CSF)促进高剂量烷基化化疗后存活的精原细胞的生精再生

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作者:Travis Kotzur, Roberto Benavides-Garcia, Jennifer Mecklenburg, Jamila R Sanchez, Matthew Reilly, Brian P Hermann

Background

The lifesaving chemotherapy and radiation treatments that allow patients to survive cancer can also result in a lifetime of side-effects, including male infertility. Infertility in male cancer survivors is thought to primarily result from killing of the spermatogonial stem cells (SSCs) responsible for producing spermatozoa since SSCs turn over slowly and are thereby sensitive to antineoplastic therapies. We previously demonstrated that the cytokine granulocyte colony-stimulating factor (G-CSF) can preserve spermatogenesis after alkylating chemotherapy (busulfan).

Conclusions

Together, these results clarify that G-CSF protects spermatogenesis after alkylating chemotherapy by stimulating proliferation of surviving spermatogonia, and indicate it may be useful as a retrospective fertility-restoring treatment.

Methods

Male mice were treated with G-CSF or controls before and/or after sterilizing busulfan treatment and evaluated immediately or 10-19 weeks later for effects on spermatogenesis.

Results

We demonstrated that the protective effect of G-CSF on spermatogenesis was stable for at least 19 weeks after chemotherapy, nearly twice as long as previously shown. Further, G-CSF treatment enhanced spermatogenic measures 10 weeks after treatment in the absence of a cytotoxic insult, suggesting G-CSF acts as a mitogen in steady-state spermatogenesis. In agreement with this

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