Influence of graft size, histocompatibility,and cryopreservation on reproductive outcome following ovary transplantation in mice

T Kolbe,I Walter,T Rülicke

doi:10.1007/s10815-019-01620-9

Abstract

PurposeTransplantation of ovarian tissue is a valuable method to rescue mouse strains with fertility problems and to revitalize archived strains. The purpose of this study was to investigate the effect of (i) different sizes of transplanted ovary pieces on reproductive outcome, (ii) use of immunodeficient recipients to overcome the limitation of histocompatibility, and (iii) to compare different protocols for cryopreservation of ovarian tissue.MethodsHalves, quarters, and eights of mouse ovaries were transplanted. Half ovaries from B6 donors were transferred into immunodeficient mice. Halves of ovaries were frozen according to four different protocols, thawed and transferred.ResultsPregnancy rate after transplantation of ovarian tissue was high (90–100%) independent of the transplant size. Although, the average litter size was significantly lower for recipients of quarters and eights (4.4 and 4.6 vs. 6.5), the total number of offspring produced per donor ovary was higher compared with recipients of halves. Pregnancy rate of immunodeficient recipients was 40% (mean 4.7 offspring per litter). All four cryopreservation protocols used were able to preserve functionality of the ovarian tissue.ConclusionsTransplantation of ovarian tissue smaller than halves resulted in reduced litter sizes. The distribution of ovarian tissue of one donor female to 4 or 8 recipients will therefore yield in a higher total number of offspring in a certain time period. The use of immunodeficient recipients is an option for non-histocompatible donors. Cryopreservation of ovarian tissue is generally feasible but the function of frozen-thawed ovary halves after transplantation differs depending on the freezing protocol used.

Highlights

Ovary transfer in mice has been used since the last century for experimental reasons [1]
A prerequisite for engraftment of transplanted tissue is the histocompatibility between donor and recipient determined by the genes of the major histocompatibility complex (MHC)
Thawing: Vials were held for 40 s at room temperature (RT) were placed into 30–37 °C warm water until thawed

Summary

Introduction

Ovary transfer in mice has been used since the last century for experimental reasons [1]. There is no systematic comparison of the transfer of different sized ovary pieces in mice. Donors of outbred strains with undefined mixed genetic background are not suitable because of the absence of appropriate histocompatible recipients. A possible strategy to overcome this incompatibility problem is to use very young recipients without a fully developed immune system [9]. This approach induces technical problems due to the small size of the very young recipients. Immunodeficient mice have frequently been used for xenotransplantation as recipients for ovary pieces from the rat [15], human [16,17,18,19,20,21], sheep [22, 23], cat [24, 25], cattle [26, 27], wombat [28], elephant [29], dog [30, 31], and lion [32]

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