Mmp2 Deficiency Leads to Defective Parturition and High Dystocia Rates in Mice

Rotem Kalev-Altman*, Gal Becker, Tamar Levy, Svetlana Penn, Nahum Y. Shpigel, Efrat Monsonego-Ornan, Dalit Sela-Donenfeld*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Parturition is the final and essential step for mammalian reproduction. While the uterus is quiescent during pregnancy, fundamental changes arise in the myometrial contractility, inducing fetal expulsion. Extracellular matrix (ECM) remodeling is fundamental for these events. The gelatinases subgroup of matrix metalloproteinases (MMPs), MMP2 and MMP9, participate in uterine ECM remodeling throughout pregnancy and parturition. However, their loss-of-function effect is unknown. Here, we determined the result of eliminating Mmp2 and/or Mmp9 on parturition in vivo, using single- and double-knockout (dKO) mice. The dystocia rates were measured in each genotype, and uterine tissue was collected from nulliparous synchronized females at the ages of 2, 4, 9 and 12 months. Very high percentages of dystocia (40–55%) were found in the Mmp2−/− and dKO females, contrary to the Mmp9−/− and wild-type females. The histological analysis of the uterus and cervix revealed that Mmp2−/− tissues undergo marked structural alterations, including highly enlarged myometrial, endometrial and luminal cavity. Increased collagen deposition was also demonstrated, suggesting a mechanism of extensive fibrosis in the Mmp2−/− myometrium, which may result in dystocia. Overall, this study describes a new role for MMP2 in myometrium remodeling during mammalian parturition process, highlighting a novel cause for dystocia due to a loss in MMP2 activity in the uterine tissue.

Original languageAmerican English
Article number16822
JournalInternational Journal of Molecular Sciences
Volume24
Issue number23
DOIs
StatePublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • MMP2
  • MMP9
  • double knockout
  • dystocia
  • fibrosis
  • gelatinase
  • matrix metalloproteinase
  • myometrium
  • uterine

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