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RO-3306 prevents postovulatory aging-mediated spontaneous exit from M-II arrest in rat eggs cultured in vitro

BACKGROUND:

Postovulatory aging-mediated spontaneous exit from metaphase-II (M-II) arrest deteriorates egg quality and limits assisted reproductive technologies outcome (ART) outcome. Present study was aimed to find out whether RO-3306, specific cyclin dependent kinase 1 (Cdk1) inhibitor could protect against postovulatory aging-mediated spontaneous exit from M-II arrest in rat eggs cultured in vitro.

METHODS:

Freshly ovulated M-II arrested eggs were exposed to various concentrations of RO-3306 for 3h in vitro. The morphological changes, percentage of spontaneous exit from M-II arrest, total and specific phosphorylation status of Cdk1, cyclin B1 level and Cdk1 activity were analyzed.

RESULTS:

Data suggest that RO-3306 protected postovulatory aging-mediated spontaneous exit from M-II arrest in a concentration-dependent manner. Postovulatory aging increased Thr14/Tyr15 phosphorylated Cdk1 level, decreased Thr161 phosphorylated Cdk1 as well as cyclin B1 levels and increased Cdk1 activity in aged eggs cultured in vitro. On the other hand, RO-3306 protected postovulatory aging-induced changes in specific phosphorylation of Cdk1, cyclin B1 level, inhibited the kinase activity and prevented spontaneous exit from M-II arrest.

CONCLUSIONS:

Our results suggest that postovulatory aging destabilizes MPF by modulating specific phosphorylation of Cdk1 and cyclin B1 level. RO-3306 prevented these changes and maintained M-II arrest in rat eggs cultured in vitro. Hence, maintenance of M-II arrest in ovulated eggs using RO-3306 could be beneficial to increase the number of eggs available for various ART programs.

Related Products

Cat.No. Product Name Information
S7747 Ro-3306 RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with Ki of 20 nM, >15-fold selectivity against a diverse panel of human kinases. RO-3306 enhances p53-mediated Bax activation and mitochondrial apoptosis.

Related Targets

CDK