Description du projet
Un nouveau protocole de fertilité pour le syndrome des ovaires polykystiques
Près d’une femme sur cinq souffre du syndrome des ovaires polykystiques (SOPK) et présente une morphologie ovarienne polykystique, un dysfonctionnement ovulatoire et une infertilité. La maturation et la compétence des ovocytes dépendent en grande partie des cellules cumulus environnantes qui fournissent des signaux paracrines via une communication de cellule à cellule. Pour déterminer le potentiel facteur causal de l’infertilité dans le SOPK, les scientifiques du projet POMOLIM, financé par l’UE, étudient le profil d’expression génique et les changements épigénétiques rencontrés dans les cellules cumulus chez ces femmes. Les résultats du projet devraient améliorer les protocoles de traitement de la fertilité pour les femmes atteintes de SOPK et faire progresser la maturation in vitro (IVM) des ovocytes SOPK comme approche alternative.
Objectif
Polycystic ovarian syndrome (PCOS) is the leading endocrine and metabolic disorder in women, with a prevalence of 5-20%. It is characterized by hyperandrogenism, ovulatory dysfunction, polycystic ovarian morphology and infertility. Epigenetic factors have garnered attention in the pathogenesis of PCOS since changes in DNA methylation and gene expression have been reported in various tissues. Whether these alterations are also found in PCOS oocytes remains unknown. Cumulus cells (CCs) are specialized cells that maintain paracrine signals and cell-to-cell communications with the oocyte to support the acquisition of competence to derive an embryo. This crosstalk is important in PCOS since the reduced oocyte competence is considered the potential causative factor of infertility. PCOS women seeking in vitro fertilization (IVF) treatments suffer greater sensitivity to hormonal treatments, which can lead to a high risk of ovarian hyperstimulation. In vitro maturation (IVM) of oocytes has been introduced in the human fertility clinic as a mild-approach alternative to conventional IVF as it requires minimal stimulation of the ovaries. However, there is a need to further develop a better protocol that curtails the 30% gap efficiency existing between IVM and IVF. This project aims to 1) generate DNA methylation and gene expression profiles of PCOS oocytes and paired CCs using single-cell and low-cell parallel sequencing, 2) create an improved, safe and robust IVM system that can increase oocyte competence for these patients and 3) define the molecular pathways that are differentially regulated in oocytes and CCs after in vitro maturation. The project will benefit from the experience in fertility treatments and safety assessment of the host supervisors, Profs. Smitz and Anckaert. The access to human material will be granted by the home institution. In addition, a secondment in Dr. Kelsey’s laboratory (Cambridge, UK) will provide pioneering single-cell technologies.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
1050 Bruxelles / Brussel
Belgique