Study Pinpoints HOXA10–TWIST2 Switch That Enables Embryo Implantation

Overview

• Researchers from IISc, ICMR–NIRRCH, and BHU report the findings in Cell Death Discovery, detailing a regulatory program for uterine receptivity.
• HOXA10 maintains a stable epithelial lining by controlling more than 1,200 genes, while a localized decline permits TWIST2 activation and a controlled hybrid EMT.
• Computational analyses show the HOXA10–TWIST2 interplay functions as a bistable genetic circuit that can switch uterine states in a reversible manner.
• Experiments in mice, hamsters, monkeys, and human cells validate the mechanism, with TWIST2 blockade preventing uterine remodeling and implantation.
• The work offers a mechanistic explanation for some implantation failures and suggests paths for IVF-focused research, with broader relevance to wound healing, fibrosis, and cancer.