Early antral follicles (EAfs) offer oocyte potential in Assisted Reproductive Technology (ART), but most fail to mature under current in vitro maturation (IVM) protocols. This study examines transcriptomic profiles of the follicular wall (FW) compartment during IVM in ovine EAfs using a 3D follicle-enclosed oocyte (FEO) culture to identify somatic gene markers predicting oocyte maturation success. Differentially expressed genes (DEGs) were identified across three comparisons: pre- vs. post-hCG in FW enclosing mature/fertilizable (1) or immature (2) oocytes, and post-hCG between FW supporting successful vs. failed maturation (3). Network analysis highlighted key modulated and HUB genes. Two DEG categories emerged: genes regulating meiosis resumption and genes defining follicular signatures linked to oocyte competence. Meiosis resumption involved ECM remodeling, hypoxia, and relaxin signaling activation, while proliferative and metabolic pathways were downregulated. MMP13 and EGFR regulated the ECM pathway, working for meiosis resumption, while TGFB1 predicted failure. Oocyte competence involves ECM activation and the suppression of stress and cell cycle pathways, with ITIH4 being conducive to central HUB tuning inflammation and angiogenesis-dependent maturation. This study reveals molecular mechanisms behind follicle maturation, identifying transcriptomic signatures for FW releasing mature/fertilizable and incompetent oocytes. It confirms known biomarkers and uncovers new regulators, offering tools to assess follicle quality, improve IVF–oocyte selection, and enhance fertility preservation.

Transcriptomic Profile of Early Antral Follicles: Predictive Somatic Gene Markers of Oocyte Maturation Outcome

Konstantinidou F.;Stuppia L.;Gatta V.
Ultimo
2025-01-01

Abstract

Early antral follicles (EAfs) offer oocyte potential in Assisted Reproductive Technology (ART), but most fail to mature under current in vitro maturation (IVM) protocols. This study examines transcriptomic profiles of the follicular wall (FW) compartment during IVM in ovine EAfs using a 3D follicle-enclosed oocyte (FEO) culture to identify somatic gene markers predicting oocyte maturation success. Differentially expressed genes (DEGs) were identified across three comparisons: pre- vs. post-hCG in FW enclosing mature/fertilizable (1) or immature (2) oocytes, and post-hCG between FW supporting successful vs. failed maturation (3). Network analysis highlighted key modulated and HUB genes. Two DEG categories emerged: genes regulating meiosis resumption and genes defining follicular signatures linked to oocyte competence. Meiosis resumption involved ECM remodeling, hypoxia, and relaxin signaling activation, while proliferative and metabolic pathways were downregulated. MMP13 and EGFR regulated the ECM pathway, working for meiosis resumption, while TGFB1 predicted failure. Oocyte competence involves ECM activation and the suppression of stress and cell cycle pathways, with ITIH4 being conducive to central HUB tuning inflammation and angiogenesis-dependent maturation. This study reveals molecular mechanisms behind follicle maturation, identifying transcriptomic signatures for FW releasing mature/fertilizable and incompetent oocytes. It confirms known biomarkers and uncovers new regulators, offering tools to assess follicle quality, improve IVF–oocyte selection, and enhance fertility preservation.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/873058
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