Transplantation of frozen-thawed late-gestational-age human fetal ovaries into immunodeficient mice

Fertil Steril. 2009 Aug;92(2):770-7. doi: 10.1016/j.fertnstert.2008.06.032. Epub 2008 Aug 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cryopreservation / methods*
  • Female
  • Fetus / cytology*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, SCID
  • Ovary / embryology*
  • Ovary / transplantation*