Transplantation of frozen-thawed late-gestational-age human fetal ovaries into immunodeficient mice
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Published on: September 7, 2016
Ronit Abir1, Tal Biron-Shental, Raoul Orvieto
1Infertility and IVF Unit, Helen Schneider Hospital for Women, Rabin Medical Center, Beilinson Hospital, Petach Tikva 49100, Israel.
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.
