Prevention of premature ovarian failure and osteoporosis induced by irradiation using allogeneic ovarian/bone marrow transplantation.
BACKGROUND
Two side effects of irradiation are premature ovarian failure (POF) and osteoporosis, both of which are concerns not only clinically, for patients, but also experimentally, for animals. We examine whether bone marrow transplantation (BMT) can correct the POF induced by radiation and also address whether allogeneic ovarian transplantation (OT) can modulate the adverse effects of radiotherapy.


METHODS
Eight-week-old female C57BL/6 mice were lethally irradiated with 6 Gy x2, and then injected with allogeneic bone marrow cells into their bone marrow cavity using our previously described intrabone marrow (IBM)-BMT technique. Allogeneic ovaries were simultaneously transplanted under the renal capsules of the mice.


RESULTS
Three months after the transplantation, we noted that hematopoietic and lymphoid cells had been successfully reconstituted. The ovaries transplanted under the renal capsules demonstrated signs of development with a large number of differentiating follicles at different stages of development. Importantly, the total bone mineral density of the tibia in the "IBM-BMT+OT" (BMT/OT) group remained normal. However, the reproductive function of the recipient mice was not restored, despite the presence of many immature oocytes in the host ovaries in the BMT/OT group. In the BMT group, no oocytes were found in the host ovaries.


CONCLUSIONS
These findings suggest that IBM-BMT with ovarian allografts can be advantageous for young women with POF and osteopenia or osteoporosis that is due to chemotherapy and radiotherapy for malignant diseases.
Feng
Wei
W
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
Cui
Yunze
Y
Zhan
Hongsheng
H
Shi
Ming
M
Cui
Wenhao
W
Guo
Kequan
K
Li
Qing
Q
Song
Changye
C
Zhang
Yuming
Y
Mori
Takahide
T
Gershwin
M Eric
ME
Abraham
Nader G
NG
Ikehara
Susumu
S
D000135:Acid Phosphatase / Q000097:blood; D000818:Animals; D001854:Bone Marrow Cells / Q000528:radiation effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D004958:Estradiol / Q000097:blood; D005260:Female; D007527:Isoenzymes / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D010053:Ovary / Q000637:transplantation*; D016649:Primary Ovarian Insufficiency / Q000209:etiology / Q000517:prevention & control*; D011878:Radiotherapy / Q000009:adverse effects*; D000071681:Tartrate-Resistant Acid Phosphatase; D014184:Transplantation, Homologous
D007527:Isoenzymes; D004958:Estradiol; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase