Défense de thèse de Jules BINDELS
Sciences biomédicales et pharmaceutiques
Infos
Le mardi 18 novembre, Monsieur Jules BINDELS, titulaire d'un Master of biomedical sciences (UMaastricht) et d'un certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, sous la direction de Madame Carine MUNAUT.
Cette épreuve consistera en la défense publique d'une thèse intitulée : "Female fertility restoration: Modulation of follicle activation linked to ovarian cryopreservation and transplantation".
Le jury sera composé de :
Michael HERFS (Président), Laurie HENRY (Secrétaire), Frédéric CHANTRAINE, Christophe DEROANNE, Marie-Madeleine DOLMANS, Stine Gry KRISTENSEN et Carine MUNAUT.
Résumé de la thèse
Cancer therapies such as chemotherapy can severely impair ovarian fuction, leading to premature ovarian failure and infertility. Ovarian tissue cryopreservation and transpnatation (OTCTP) is currently the only fertility preservation option for prepubertal girls and women requiring urgent treatment. Despite its clinical success, OTCTP is limited by post-grafting follicle loss due to ischemia, apoptosis, and primordial follicle (PMF) hyperactivation.
To address this, we developed a novel, minimally invasive ear transplantation model allowing localized post-grafting drug delivery. Compared to the conventional kidney capsule model, PI3K inhibition with LY294002 produced similar effects on follicle activation, validating the new model’s utility for testing pharmacological interventions.
We then assessed whether adding the mTOR inhibitor rapamycin during cryopreservation could improve OTCTP outcomes. Rapamycin preserved follicle quiescence and improved fertility restoration in vivo, but triggered compensatory Akt activation. Therefore, we tested BEZ235, a dual PI3K/mTOR inhibitor. BEZ235 preserved the PMF pool and reduced follicle activation more effectively than single inhibitors, both in vitro and in vivo.
Thus, dual PI3K/mTOR inhibition with BEZ235 offers a promising strategy to reduce follicle loss after OTCTP. As fertility preservation is becoming increasingly important for young cancer patients, such strategies may help extend their reproductive lifespan and quality of life post-treatment.
