Functional corpora lutea are formed in matrix metalloproteinase inhibitor-treated plasminogen-deficient mice

Endocrinology. 2007 Mar;148(3):1226-34. doi: 10.1210/en.2006-0669. Epub 2006 Nov 22.

Abstract

Corpus luteum (CL) formation involves dramatic tissue remodeling and angiogenesis. To determine the functional roles of the plasminogen activator and matrix metalloproteinase (MMP) systems in these processes, we have studied CL formation and function in plasminogen (plg)-deficient mice, with or without treatment with the broad-spectrum synthetic MMP inhibitor galardin. Both the adult pseudopregnant CL model and the gonadotropin-primed immature mouse model were used. We found that CL formed normally not only in plasminogen-deficient mice and in galardin-treated wild-type mice, but also in galardin-treated plg-deficient mice, suggesting that neither of the plasminogen activator and MMP systems is essential for CL formation. Nevertheless, in plg-deficient mice, serum progesterone levels were reduced by approximately 50%, and the progesterone levels were not reduced further by galardin treatment. When CL from plg-deficient mice were stained for several molecular markers for CL development and regression, they appeared healthy and vascularized, and were indistinguishable from CL from wild-type mice. This implies that the reduced progesterone levels were not caused by impaired CL formation. Taken together, our data suggest that neither plasmin nor MMPs, alone or in combination, are required for CL formation. Therefore, the tissue remodeling and angiogenesis processes during CL formation may be mediated by redundant protease systems. However, the reduced serum progesterone levels in plg-deficient mice suggest that plasmin, but not MMPs, plays a role in maintenance of luteal function. This role may be performed through proteolytic activation of growth factors and other paracrine factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Luteum / blood supply
  • Corpus Luteum / drug effects*
  • Corpus Luteum / physiology*
  • Dipeptides / pharmacology
  • Female
  • Gonadotropins / pharmacology
  • Male
  • Matrix Metalloproteinase Inhibitors*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasminogen / genetics*
  • Progesterone / blood
  • Pseudopregnancy / blood

Substances

  • Dipeptides
  • Gonadotropins
  • Matrix Metalloproteinase Inhibitors
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Progesterone
  • Plasminogen