Follicular growth after xenotransplantation of cryopreserved/thawed human ovarian tissue in SCID mice: dynamics and molecular aspects

Abstract

PurposeTo study the influence of xenotransplantation on follicular recruitment and growth in cryopreserved/thawed human ovarian tissue.MethodTwo 3-mm pieces of cryopreserved/thawed human ovarian tissue obtained from female cancer patients (n = 11) were xenotransplanted into a subcutaneous neck pouch of 6-week-old ovarectomized SCID mice (n = 33) for 4 (n = 18) and 12 (n = 15) weeks.ResultThirty-two out of 33 mice survived the entire observation periods. Graft recovery rate was 95.58 % (65 of 68 grafts). The percentages of primordial follicles after 4 weeks (P < 0.001) and 12 weeks (P = 0.009) of grafting were significantly lower in comparison to pregraft controls. The percentage of secondary follicle was significantly higher after 4 weeks of grafting (P = 0.018) and after 12 weeks (P = 0.001) of grafting in comparison to pregraft controls. Ki67 immunohistochemistry showed that proliferative follicles were significantly higher after 4 and 12 weeks of grafting compared to pregraft controls (P < 0.001). All follicles analyzed by TUNEL staining appeared healthy after xenotransplantation. The expression level of PTEN was reduced by 2.47-fold after 4 weeks of xenotransplantation, and this result was significant when 2−ΔCt were analyzed (P = 0.042).ConclusionThe higher proportion of growing follicles compared to resting follicles observed after xenotransplantation is most likely due to downregulation of PTEN gene expression followed by acceleration of follicular recruitment.Electronic supplementary materialThe online version of this article (doi:10.1007/s10815-016-0769-2) contains supplementary material, which is available to authorized users.

FERTILITY PRESERVATION: Follicle reserve loss in ovarian tissue transplantation

“…The significant primordial follicles loss that occurs shortly after transplantation has been shown to be simultaneously accompanied by a significant increase in early growing follicles populations and increased proliferation of granulosa cells in transitional and early growing follicles (Oktay et al 2000b, Dolmans et al 2007, Dath et al 2010, Amorim et al 2011, Ayuandari et al 2016, Gavish et al 2018 (Fig. 2).…”

Ovarian tissue transportation: a systematic review

“…Some studies have used in vitro culture of ovarian fragments, but this system is not very well established for many species, yielding low rates of follicle survival in both short-and long-term culture (Isachenko et al 2006, Smitz et al 2010, Vilela et al 2016. Since ovarian tissue transplantation has already been validated for cryopreservation assessment (Nottola et al 2008, Amorim et al 2011, Luyckx et al 2013, Ayuandari et al 2016, Ruan et al 2019, Vilela et al 2019, it might be a valuable technique to evaluate tissue transport. Indeed, transplantation of mouse ovarian tissue was used to assess ovarian tissue storage and revealed a significant reduction in both implantation and live birth rates, even though the morphology before transplantation did not show any difference in the percentage of morphologically normal follicles (Kamoshita et al 2016).…”

State of the Art in Fertility Preservation for Female Patients Prior to Oncologic Therapies

“…It has been described as a 'burn out effect', and there is still debate around the implicated mechanisms. One study concluded that the increased number of growing follicles versus resting follicles might be due to the downregulation of PTEN gene expression and subsequent augmentation of follicular recruitment [57]. A Japanese team led by Kawamura [58] recently proposed a premature ovarian insufficiency treatment by Hippo signaling dysregulation, realized by fragmenting ovarian tissue followed by Akt application and autografting.…”