Dolmans, Marie-MadeleineVassart, SarahSarahVassart2025-05-142025-05-142025-05-142022https://hdl.handle.net/2078.2/28834Turner syndrome (TS) is caused by complete or partial absence of one of the two X chromosomes in women, and most commonly results in short stature and malfunctioning ovaries. It is known that most women with TS experience a premature decline or complete loss of fertility due to accelerated gamete loss. Cryopreservation of ovarian tissue is already routinely offered to TS patients (especially to patients with mosaicism and less severe ovarian depletion), but the efficacy of fertility restoration is still unknown, since there are no reports on autotransplantation followed by pregnancy in this population so far. This study aims to determine if frozen-thawed ovarian tissue from a TS patient is viable after transplantation and able to produce mature eggs. The case series includes 18 females diagnosed with numerical X chromosome aberrations (45,X or mosaic karyotype) and 13 age-matched controls. For each patient, two thawed ovarian cortex fragments were analyzed (i) directly after thawing and (ii) after xenografting for five months. The analyses performed included (i) follicle density and abnormal morphology rates by histology; (ii) follicle morphology by transmission electron microscopy; (iii) expression of proliferating cell nuclear antigen (PCNA) and anti-Müllerian hormone (AMH) and, two key oocyte-derived growth factors, GDF9 and BMP15, by immunohistochemistry; (iv) expression of a ligand- receptor system involved in oocyte survival, kit ligand and c-Kit, by immunofluorescence; (v) X chromosome content in oocytes and granulosa cells (GCs) by fluorescent in situ hybridization; and (vi) predictive factors establishment for development of ovarian follicles to mature stages (antral follicles). The results of this study showed that the development of follicles up to the antral stage was detected in the transplanted tissues of some TS patients. However, the follicle density of cryopreserved ovarian tissue from TS patients was significantly lower than in controls, in thawed tissue and after transplant. Although GDF9 secretion from the oocyte remained unchanged in Turner patients, BMP15 secretion in small follicles were impaired and did not recover after xenotransplantation. High GC proliferation within primordial follicles in Turner patients was also noted after transplantation. Nevertheless, the xenografted TS tissues analyzed showed better parameters too; reduced abnormal follicle levels, restored GC functions, and reduced aneuploidy rates within GCs among the mature follicles. Results showed that TS patients with peri-/post-pubertal status had the poorest outcomes in terms of existing follicle density and survival rates after transplantation. Then, although the sooner the better, this study suggested using the age below 12 years to predict the possibility of small follicles from TS frozen ovarian tissue reaching normal development to the ovulatory stage after autotransplantation. In short, this study showed that even after transplantation, outcomes were still poorer in Turner patients. Moreover, some of them (4 out of 16) already showed a total loss of follicles after 5 months of transplantation. It would thus seem that a small percentage of this patient population could actually benefit from this cryopreserved ovarian tissue autotransplantation.Turner syndromeCryopreservationTransplantationOvaryFertilitytext::thesis::master thesisthesis:38333