Descrizione del progetto
Nuovo protocollo di fertilità per la sindrome dell’ovaio policistico
Quasi una donna su cinque soffre di sindrome dell’ovaio policistico (PCOS, Polycystic Ovary Syndrome) e presenta morfologia policistica dell’ovaio, disfunzione ovulatoria e infertilità. La maturazione e la competenza degli ovociti dipendono in gran parte dalle cellule del cumulo ooforo circostanti che forniscono segnali paracrini attraverso la comunicazione cellula-cellula. Per determinare il potenziale fattore causale di infertilità nella sindrome dell’ovaio policistico, gli scienziati del progetto POMOLIM, finanziato dall’UE, stanno studiando il profilo di espressione genica e i cambiamenti epigenetici riscontrati nelle cellule del cumulo ooforo in queste donne. I risultati del progetto dovrebbero migliorare i protocolli di trattamento della fertilità per le donne affette da sindrome dell’ovaio policistico e far progredire la maturazione in vitro (MIV) degli ovociti PCOS come approccio alternativo.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
1050 Bruxelles / Brussel
Belgio