Transcriptomic Profiling Reveals Urokinase-Type Plasminogen Activator-Mediated Regulation of Metabolic Competence and Cumulus Expansion During Mouse Oocyte In Vitro Maturation

TL;DR

This study shows that a protein called PLAU helps mouse oocytes mature in the lab by regulating metabolism and cumulus cell expansion.

Contribution

The study identifies PLAU as a key regulator of metabolic competence and cumulus expansion during mouse oocyte in vitro maturation.

Findings

Serum and PLAU enhance cumulus expansion and oocyte maturation, while their absence or inhibition hinders these processes.

PLAU inhibition reduces genes related to glycolysis and metabolism but increases those involved in vesicle transport.

Adding PLAU to serum-free conditions partially rescues maturation and expansion defects.

Abstract

In vitro maturation (IVM) of mammalian oocytes is an essential fertility option for patients at risk of ovarian hyperstimulation syndrome or needing urgent fertility preservation. However, poor outcomes indicate a limited understanding of the molecular mechanisms behind cumulus cell expansion and extracellular matrix (ECM) remodeling. This study investigated the role of serum-derived urokinase-type plasminogen activator (PLAU) in mouse oocyte IVM. Immature cumulus–oocyte complexes from CD-1 mice were cultured with or without serum, and PLAU activity was blocked using 4-chlorophenylguanidine hydrochloride. Cumulus expansion, oocyte maturation, and cumulus cell transcriptomes were analyzed. Serum supplementation enhanced cumulus expansion and maturation, while absence of serum or PLAU inhibition hindered both processes. External PLAU partially rescued these issues under serum-free conditions. Transcriptome analysis demonstrated that inhibiting PLAU activity reduces the expression of ovulation- and metabolism-related genes, such as those involved in glycolysis and carbohydrate metabolism, while increasing genes related to vesicle-mediated transport. PLAU is crucial for cumulus expansion and metabolic regulation during IVM, affecting ECM remodeling and oocyte quality. Supporting IVM culture media with proteolytic and metabolic factors could improve outcomes in assisted reproduction.

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