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Polycystic ovarian syndrome: novel molecular characterization and personalized in vitro maturation protocol.

Project description

New fertility protocol for polycystic ovary syndrome

Nearly one in five women suffers from polycystic ovary syndrome (PCOS) and presents with polycystic ovarian morphology, ovulatory dysfunction and infertility. Oocyte maturation and competence largely depend on the surrounding cumulus cells which provide paracrine signals through cell-to-cell communication. To determine the potential causative factor of infertility in PCOS, scientists of the EU-funded POMOLIM project are investigating the gene expression profile and epigenetic changes encountered in cumulus cells in these women. The project's results are expected to improve fertility treatment protocols for women with PCOS and advance in vitro maturation (IVM) of PCOS oocytes as an alternative approach.

Objective

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.

Coordinator

VRIJE UNIVERSITEIT BRUSSEL
Net EU contribution
€ 166 320,00
Address
PLEINLAAN 2
1050 Bruxelles / Brussel
Belgium

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Region
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 166 320,00