Projektbeschreibung
Neue Fruchtbarkeitsbehandlung bei polyzystischem Ovar-Syndrom
Etwa eine von fünf Frauen leidet am polyzystischen Ovar-Syndrom, das mit Zysten in den Eierstöcken, Störungen des Eisprungs sowie Unfruchtbarkeit einhergeht. Reifung und Funktionsfähigkeit einer Eizelle hängen vor allem von den umliegenden Cumuluszellen ab, die durch Zelle-zu-Zelle-Kommunikation parakrine Signale aussenden. Um den möglichen ursächlichen Faktor für Unfruchtbarkeit bei polyzystischem Ovar-Syndrom zu finden, untersucht das Forschungsteam des EU-finanzierten Projekts POMOLIM bei betroffenen Frauen das Profil der Genexpression sowie epigenetische Veränderungen in den Cumuluszellen. Die Projektergebnisse werden das Vorgehen bei Fruchtbarkeitsbehandlungen von Frauen mit polyzystischem Ovar-Syndrom verbessern und die In-vitro-Maturation von Eizellen als alternative Option weiterentwickeln.
Ziel
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.
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordinator
1050 Bruxelles / Brussel
Belgien