Infertility is a devastating adverse effect of systemic chemotherapy. Hematopoietic cell transplantation (HCT) is now a treatment for chemotherapy-induced ovarian failure. HCT is the treatment of choice for many malignancies and non-cancerous conditions. Full donor chimerism is frequently seen in the hematopoietic system. Recent experimental models and studies in HCT recipients have documented donor cells in vascular endothelium, various organs, and even in the recipient’s fingernails. This recent report from Lee, et al. adds another twist to these observations. We have known that the preparatory regimens for HCT are associated with near absolute ovarian failure and infertility due to the ablative regimens utilized (although, there have been reports of pregnancies especially in younger women). The current dogma is that women are born with a fixed number of oocytes that are not replenished and that the chemotherapy with or without radiation destroys the oocytes. This dogma was challenged in 2005 when investigators reported in a controversial manuscript that adult mice continued to produce new eggs and that these eggs could have arisen from bone marrow cells.1 In this current study, Lee, et al. tested if and how HCT (in this case using murine marrow cells) could restore fertility in mice treated with chemotherapy. Females administered nonlethal doses of chemotherapy (12 mg/kg of busulfan and 120 mg/kg of cyclophosphamide) without HCT became infertile, with the majority (10 of 13 mice) achieving three or fewer live-birth pregnancies and none achieving six live-birth pregnancies. On the other hand, 90 percent of the mice that received HCT one week after the same chemotherapy achieved at least four live-birth pregnancies, 80 percent (eight of 10 mice) achieved five pregnancies, and 70 percent (seven of 10 mice) achieved six pregnancies. It is important to note that in this preclinical model, the mice were six to 10 weeks old. (They were quite young.)
In Brief
The data demonstrate that if HCT is performed within one week of the chemotherapy, the procedure leads to restoration of long-term fertility. To the investigators’ surprise, while they were able to track a few donor-derived oocytes in the ovaries, the pups were of recipient origin (none were of donor origin). What happened in these studies? Is the ovary similar to the testes where the germ cells continuously generate new gametes? The data suggest that the infusion of donor bone marrow cells led to the rescue of a significant number of recipient follicles. These data are reminiscent of effects of other cell populations, such as mesenchymal stem cells, where the effect is that of repair or recruitment of endogenous host cells that allow for repair of the cell of interest or of the stromal support cells. The data raise many questions. Is the infusion of bone marrow cells simply enhancing clearance of damaged cells, decreasing inflammation, re-establishing stromal/nurse cells, enhancing overall health, recruiting important host cells to help with fertility, or restarting the production of oocytes? Regardless of the answers that will come with further research, if bone-marrow-derived cells can help preserve fertility, this could go a long way in mitigating one of the most devastating adverse events for young women receiving systemic chemotherapy.
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Competing Interests
Dr. Chao indicated no relevant conflicts of interest.
