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Journal Article
Research Support, Non-U.S. Gov't
Transplantation of frozen-thawed late-gestational-age human fetal ovaries into immunodeficient mice.
Fertility and Sterility 2009 August
OBJECTIVE: To compare the development of human fetal follicles from late-gestational-age fetuses frozen-thawed gradually and slowly with dimethylsulfoxide (DMSO) or 1,2 propanediol (PROH) and sucrose after renal grafting into follicle stimulating hormone-treated immunodeficient mice.
DESIGN: Controlled histologic study of grafted human fetal ovaries.
SETTING: Major tertiary care academic center.
PATIENT(S): Eleven women undergoing pregnancy termination at 22 to 33 gestational weeks.
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Microscopic morphometric analysis and immunohistochemistry for proliferating cell nuclear antigen (PCNA).
RESULT(S): Only follicles from samples frozen-thawed with PROH developed to secondary and antral stages 4 to 6 months after grafting, with PCNA expression in their granulosa cells. However, the number of surviving/developing follicles per section was very low (4-25 per graft), compared with 71 to 406 follicles in pretransplantation samples. Graft recovery was very high, with similar rates for transplants frozen-thawed with PROH and DMSO. Normal ovarian structure after grafting was identified only in the PROH frozen-thawed grafts. In deteriorated grafts, frozen-thawed with either DMSO or PROH, net-like hollows replaced follicles, whereas tubule-like structures were only identified in DMSO frozen-thawed grafts.
CONCLUSION(S): This is the first report of the development of late-pregnancy-stage human fetal follicles in immunodeficient mice. PROH freezing-thawing supported development and survival better than DMSO. However, the low follicular survival points to the urgent need for efficient methods to enhance vascularization rate and prevent ischemia.
DESIGN: Controlled histologic study of grafted human fetal ovaries.
SETTING: Major tertiary care academic center.
PATIENT(S): Eleven women undergoing pregnancy termination at 22 to 33 gestational weeks.
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Microscopic morphometric analysis and immunohistochemistry for proliferating cell nuclear antigen (PCNA).
RESULT(S): Only follicles from samples frozen-thawed with PROH developed to secondary and antral stages 4 to 6 months after grafting, with PCNA expression in their granulosa cells. However, the number of surviving/developing follicles per section was very low (4-25 per graft), compared with 71 to 406 follicles in pretransplantation samples. Graft recovery was very high, with similar rates for transplants frozen-thawed with PROH and DMSO. Normal ovarian structure after grafting was identified only in the PROH frozen-thawed grafts. In deteriorated grafts, frozen-thawed with either DMSO or PROH, net-like hollows replaced follicles, whereas tubule-like structures were only identified in DMSO frozen-thawed grafts.
CONCLUSION(S): This is the first report of the development of late-pregnancy-stage human fetal follicles in immunodeficient mice. PROH freezing-thawing supported development and survival better than DMSO. However, the low follicular survival points to the urgent need for efficient methods to enhance vascularization rate and prevent ischemia.
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