It has been suggested that germline stem cells maintain oogenesis in postnatal mouse ovaries. Here we show that adult mouse ovaries rapidly generate hundreds of oocytes, despite a small premeiotic germ cell pool. In considering the possibility of an extragonadal source of germ cells, we show expression of germline markers in bone marrow (BM). Further, BM transplantation restores oocyte production in wild-type mice sterilized by chemotherapy, as well as in ataxia telangiectasia-mutated gene-deficient mice, which are otherwise incapable of making oocytes. Donor-derived oocytes are also observed in female mice following peripheral blood transplantation. Although the fertilizability and developmental competency of the BM and peripheral blood-derived oocytes remain to be established, their morphology, enclosure within follicles, and expression of germ-cell- and oocyte-specific markers collectively support that these cells are bona fide oocytes. These results identify BM as a potential source of germ cells that could sustain oocyte production in adulthood.

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IMPORTANCEDuring hospitalization for hematopoietic stem cell transplantation (HCT), patients receive high-dose chemotherapy before transplantation and experience significant physical and psychological symptoms and poor quality of life (QOL).OBJECTIVE To assess the effect of inpatient palliative care on patient-and caregiver-reported outcomes during hospitalization for HCT and 3 months after transplantation.DESIGN, SETTING, AND PARTICIPANTS Nonblinded randomized clinical trial among 160 adults with hematologic malignancies undergoing autologous/allogeneic HCT and their caregivers (n = 94). The study was conducted from August 2014 to January 2016 in a Boston hospital; follow-up was completed in May 2016.INTERVENTIONS Patients assigned to the intervention (n=81) were seen by palliative care clinicians at least twice a week during HCT hospitalization; the palliative intervention was focused on management of physical and psychological symptoms. Patients assigned to standard transplant care (n=79) could be seen by palliative care clinicians on request.MAIN OUTCOMES AND MEASURES Primary: change in patient QOL from baseline to week 2; secondary: patient-assessed mood, fatigue, and symptom burden scores at baseline, 2 weeks, and 3 months after HCT and caregiver-assessed QOL and mood at baseline and 2 weeks after HCT. RESULTS Among 160 patients (mean age, 60 [SD, 13.3] years; 91 women [56.9%]; median hospital stay, 21 days) and 94 caregivers, 157 (98.1%) and 89 (94.7%), respectively, completed 2-week followup, and 149 patients (93.1%) completed 3-month follow-up. Intervention patients reported a smaller decrease in QOL from baseline to week 2 vs controls. Intervention patients had less increase in depression,loweranxiety,nodifferenceinfatigue,andlessincreaseinsymptomburden.At3months, intervention patients had higher QOL and less depression but no significant differences in anxiety, fatigue, or symptom burden. From baseline to week 2 after HCT, caregivers of intervention patients vs controls reported no significant differences in QOL or anxiety but had a smaller increase in depression (mean, 0.25 vs 1.80; mean difference, 1.55; 95% CI, 0.14-2.96; P = .03). Patient Outcomes Mean Score at Week 2 Mean Difference Between Groups (95% CI) P Value Standard Care Palliative Care Quality of life (change from baseline) −21.54 −14.72 −6.82 (−13.48 to −0.16) .045 Fatigue −13.65 −10.30 −3.34 (−7.25 to 0.56) .09 Symptom burden 23.14 17.35 5.80 (0.49 to 11.10) .03 Depression 3.92 2.43 1.49 (0.20 to 2.78) .02 Anxiety 1.12 −0.80 1.92 (0.83 to 3.01) <.001CONCLUSIONS AND RELEVANCE Among adults at a single institution undergoing HCT for hematologic malignancy, the use of inpatient palliative care compared with standard transplant care resulted in a smaller decrease in QOL 2 weeks after transplantation. Further research is needed for replication and to assess longer-term outcomes and cost implications.