Descripción del proyecto
Nuevo protocolo de fertilidad para el síndrome de ovario poliquístico
Casi una de cada cinco mujeres padece del síndrome de ovario poliquístico (SOPQ) y presenta una morfología ovárica poliquística, disfunción ovulatoria e infertilidad. La maduración y la capacidad del ovocito dependen en gran medida de las células del cúmulo que lo rodean, que proporcionan señalización paracrina a través de la comunicación intercelular. Para determinar el posible factor causal de la infertilidad en el SOPQ, los científicos del proyecto financiado con fondos europeos POMOLIM están investigando el perfil de expresión génica y los cambios epigenéticos en las células del cúmulo de estas mujeres. Se espera que los resultados del proyecto mejoren los protocolos de los tratamientos de fertilidad para las mujeres con SOPQ y hagan avanzar la maduración «in vitro» (MIV) de ovocitos de mujeres con SOPQ como método alternativo.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
1050 Bruxelles / Brussel
Bélgica