Abstract
The migratory and matrix-invading capacities of the cumulus–oocyte complex have been shown to be important for the ovulatory process. In metastatic cancers, these capacities are due to increased expression of proteases, however, there is limited information on protease expression in the cumulus–oocyte complexes. The present study examined cumulus–oocyte complex expression of plasmins, matrix metalloproteases, and A Disintegrin and Metalloproteinase with Thrombospondin Motifs family members in the rat and human. In the rat, human chorionic gonadotropin (hCG) administration increased cumulus–oocyte complex expression of Mmp2, Mmp9, Mmp13, Mmp14, Mmp16, Adamts1, and the protease inhibitors Timp1, Timp3, and Serpine1 by 8–12 h. This ovulatory induction of proteases in vivo could be mimicked by forskolin and ampiregulin treatment of cultured rat cumulus–oocyte complexes with increases observed in Mmp2, Mmp13, Mmp14, Mmp16, Mmp19, Plat, and the protease inhibitors Timp1, Timp3, and Serpine1. Comparison of expression between rat cumulus–oocyte complexes and granulosa cells at the time of ovulation showed decreased Mmp9 and increased Mmp13, Mmp14, Mmp16, Adamts1, Timp1, and Timp3 expression in the cumulus– oocyte complexes. In human, comparison of expression between cumulus and granulosa cells at the time of in vitro fertilization retrieval showed decreased MMP1, MMP2, MMP9, and ADAMTS1, while expression of MMP16, TIMP1, and TIMP3 were increased. Treatment of expanding rat cumulus–oocyte complexes with a broad spectrum matrix metalloproteases inhibitor, GM6001, significantly reduced the migration of cumulus cells in vitro. These data provide evidence that multiple proteases and their inhibitors are expressed in the cumulus–oocyte complex and play an important role in imparting the migratory phenotype of the cumulus–oocyte complex at the time of ovulation.
Document Type
Article
Publication Date
7-2024
Digital Object Identifier (DOI)
https://doi.org/10.1093/biolre/ioae108
Funding Information
This work was supported by National Institutes of Health Grants HD057446 (TEC), HD071875 (TEC), and by the Lalor Foundation Postdoctoral Fellowship (PRH).
Repository Citation
Shrestha, Ketan; Puttabyatappa, Muraly; Wynn, Michelle Arelia Ann; Hannon, Patrick R.; Al-Alem, Linah; Rosewell, Katherine L.; Akin, James; and Curry, Thomas E., "Protease expression in the human and rat cumulus–oocyte complex during the periovulatory period: a role in cumulus–oocyte complex migration" (2024). UK CARES Faculty Publications. 31.
https://uknowledge.uky.edu/ukcares_facpub/31
Notes/Citation Information
© The Author(s) 2024. Published by Oxford University Press behalf of Society for the Study of Reproduction. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.