Graft site and gonadotrophin stimulation influences the number and quality of oocytes from murine ovarian tissue grafts

Abstract

Ovarian tissue cryopreservation and subsequent transplantation can restore fertility in cancer patients. This study used a mouse ovarian grafting model to investigate whether the graft site (bursal cavity, the kidney capsule or subcutaneous) influences the number, fertilization rate and developmental potential of oocytes recovered from grafts and whether using a standard gonadotrophin stimulation protocol would increase oocyte yield from the grafts. Mouse ovarian tissue was grafted into four week old mice and collected three weeks later. Graft recipients were treated either with or without exogenous gonadotrophin stimulation prior to graft collection. Grafted ovaries yielded oocytes that were either at the germinal vesicle (GV) stage or mature metaphase II (MII) stage at collection. These GV oocytes were matured before in vitro fertilization (IVF), while the MII oocytes underwent IVF immediately. Oocytes collected from the oviducts of non-grafted superovulated mice of the same age served as controls. Two-cell embryos were transferred to pseudopregnant recipients and recovered at day 15 of gestation or left to go to term. Graft retrieval and the number of oocytes from each graft were lowest from the subcutaneous graft site. The number of two-cell embryos produced was significantly higher for oocytes from the grafts to the bursa as compared with the other sites. All graft sites gave rise to embryos with comparable implantation rates and developmental potential to fetuses and offspring following transfer. However, the oocytes from grafted ovaries had a significantly lower developmental potential when compared with the control group. Stimulation with exogenous gonadotrophins did not significantly increase oocyte yield from grafted ovaries but did enhance oocyte maturation and development. In conclusion, graft site affects the number and quality of oocytes produced from ovarian grafts.

Follicle growth and oocyte development after ovary transplantation into back muscle of immune-intact adult castrated male mice

“…Renal envelopes were highly preferred in the past, and the transplanted ovaries developed well there (Carroll et al 1990, Waterhouse et al 2004. In recent years, subcutaneous and muscle tissues have become the alternative sites for ovary implants (Oktay et al 2003, Lee et al 2004, Yang et al 2006, Schubert et al 2008, Soleimani et al 2008, Eimani et al 2009). Ovarian transplantation under the kidney capsule requires a more difficult surgical operation, and the development of grafts cannot be observed during the process.…”

Abnormally low expression of connexin 37 and connexin 43 in subcutaneously transplanted cryopreserved mouse ovarian tissue

“…However, there were few good quality embryos, and successful pregnancy did not occur. In mice, graft survival was poorer and the number of oocytes retrieved was lower from subcutaneous compared with other graft sites [18]. Cryopreserved ovarian tissues are subject to freezing, thawing, and ischemic injury throughout the transplantation procedure.…”

Effect of graft site and gonadotrophin treatment on follicular development of canine ovarian grafts transplanted to NOD‐SCID mice

“…Hernandez-Fonseca et al [38] showed that human ovarian cortical grafts transplanted under the KC had significantly higher proportions of growing follicles compared with those recovered from the SC. Furthermore, Yang et al [39] showed that graft recovery rate and oocyte yield were significantly less at the SC graft site with only 56-58% of the grafts recovered compared with the OB and KC which had 98-100% and 93-95% of the grafts retrieved, respectively. The number of two-cell embryos produced was significantly higher with oocytes from grafts to the OB, compared with KC and SC graft sites [39].…”

“…Furthermore, Yang et al [39] showed that graft recovery rate and oocyte yield were significantly less at the SC graft site with only 56-58% of the grafts recovered compared with the OB and KC which had 98-100% and 93-95% of the grafts retrieved, respectively. The number of two-cell embryos produced was significantly higher with oocytes from grafts to the OB, compared with KC and SC graft sites [39]. Our present study also showed that the effect of gonadotrophins on follicular development after xenografting was influenced by the site of transplantation.…”