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.
Highlights
The numbers of long-term cancer survivors are steadily increasing during the last decades leading to an actual 5-year survival rate for children of 79 % [1]
One of the common and serious long-term side effects related to cancer therapy in female patients is premature ovarian failure (POF)
Data from three fertility preservation centers showed that endocrine ovarian function can be restored in 93 % of patients after autotransplantation [23]
Summary
The numbers of long-term cancer survivors are steadily increasing during the last decades leading to an actual 5-year survival rate for children of 79 % [1]. Chemotherapeutic agents and irradiation are known to induce POF through destruction of ovarian follicular reserve by different mechanisms depending on the age of the patients, as well as on the type and the dose of cytotoxic agents [2,3,4,5,6] To overcome this problem, several multidisciplinary strategies have been established to preserve female fertility [7,8,9,10,11]. Clinical data showed decreased ovarian reserve and low response to ovarian stimulation in patients after ovarian tissue autotransplantation [25, 26] This decreased ovarian reserve after transplantation was proven by the low concentrations of anti-Mullerian hormone (AMH) and inhibin B as well as high levels of folliclestimulating hormone (FSH) [25,26,27]. This indicates that further studies are needed to improve the outcome of ovarian tissue cryopreservation followed by autotransplantation
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