2. Academic Validation
  3. Non-muscle myosin II-dependent cumulus cell migration at ovulation is required for sperm to reach the egg in mice

Non-muscle myosin II-dependent cumulus cell migration at ovulation is required for sperm to reach the egg in mice

  • Commun Biol. 2025 Sep 24;8(1):1357. doi: 10.1038/s42003-025-08736-y.
Karen Freire Carvalho 1 2 3,  Hugh J Clarke 4 5 6
Affiliations

Affiliations

  • 1 Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
  • 2 Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
  • 3 Azrieli Centre for Research, CHU Sainte-Justine Research Institute, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
  • 4 Division of Experimental Medicine, McGill University, Montreal, QC, Canada. Hugh.clarke@mcgill.ca.
  • 5 Research Institute of the McGill University Health Centre, Montreal, QC, Canada. Hugh.clarke@mcgill.ca.
  • 6 Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada. Hugh.clarke@mcgill.ca.
PMID: 40993317 DOI: 10.1038/s42003-025-08736-y
Abstract

At ovulation in mammals, epidermal growth factor (EGFR) signaling in the cumulus granulosa cells that enclose the egg causes them to generate an extracellular matrix and become dispersed within it. This process, termed expansion, is required for sperm to reach the egg. The extracellular signal-related kinase (ERK) pathway mediates matrix production, but the mechanism responsible for cell dispersion is poorly understood. We show that EGFR signaling activates non-muscle Myosin II (NMII) in the cumulus cells and that NMII activity is required for full expansion. NMII activation does not require ERK signaling, but instead depends on the Rho-associated coiled-coil containing kinases (ROCK) and the myotonic dystrophy kinase-related CDC42-binding kinases (MRCK). Blocking ROCK or MRCK impairs the ability of the cumulus cells to migrate and reduces the number of sperm that penetrate through the cumulus layer to reach the oocyte. EGFR thus promotes cumulus layer expansion by integrating ERK-dependent production of the matrix with NMII-dependent migration of the cumulus cells within it.

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