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Chemotherapy and ovarian tissue : From damage characterization, to novel protection strategies

van der Plancke, Graziella
(2025)

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vanderPlancke_Graziella_9318-23-00_2025.pdf
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Details

Supervisors
Dolmans, Marie-Madeleine
Faculty
Faculté de pharmacie et des sciences biomédicales
Degree label
Master [120] en sciences biomédicales, à finalité approfondie
Abstract
Advances in early diagnosis and treatment of cancer have significantly improved survival rates, bringing fertility preservation to the forefront of cancer care. Among available fertility preservation strategies, ovarian tissue cryopreservation (OTC) offers a unique option for prepubertal girls and women who cannot postpone chemotherapy. Nevertheless, OTC is generally contraindicated in patients who have undergone prior chemotherapy, despite recent clinical studies indicating that low-dose chemotherapy before OTC does not significantly impact outcomes after transplantation. Meanwhile, new research is focusing on protecting the ovaries during chemotherapy through innovative gonadoprotective approaches. This study aimed to (i) investigate the histological effects of low-dose chemotherapy on human ovarian tissue to refine selection criteria for OTC, and (ii) assess the efficacy of two gonadoprotective agents in a murine model of chemotherapy-induced ovarian damage. (i) Effects of low-dose alkylating agents on human ovarian tissue The effects of low-dose alkylating agents on human ovarian tissue were assessed through a retrospective study comparing biopsy samples from patients who had undergone OTC after low-dose chemotherapy and from chemotherapy-free patients. Ovarian damage was evaluated by investigating the ovarian reserve (hematoxylin and eosin [H&E] staining), follicle apoptosis (cleaved caspase-3 immunohistochemistry [IHC]), follicle activation (p-Akt IHC) and stromal damage (Masson’s trichrome for fibrosis with von Willebrand factor and alpha smooth muscle actin double immunofluorescence for vascularization). Results revealed no significant differences between chemotherapy-exposed and chemotherapy-free tissue, indicating that low-dose chemotherapy does not impair ovarian tissue quality for cryopreservation. (ii) Gonadoprotection by temsirolimus and anti-Müllerian hormone against chemotherapy-induced follicle overactivation The protective effects of temsirolimus and anti-Müllerian hormone were evaluated in a murine model of chemotherapy-induced ovarian damage. Fertility outcomes (embryo count), ovarian reserve (H&E staining), follicle apoptosis (cleaved caspase-3 IHC), activation (p-Akt IHC) and proliferation (Ki67 IHC) were explored. Data pointed to their potential promise as gonadoprotective agents, capable of preserving the ovarian reserve and fertility following chemotherapy.