Basal membrane remodeling during follicle histogenesis in the rat ovary: contribution of proteinases of the MMP and PA families.
In mammalian females, follicular units arise from the fragmentation of ovigerous cords, which spread over the first three postnatal days in the rat. The mechanisms underlying such a process of epithelial remodeling involve a specific balance between basal membrane (BM) deposition and degradation that has as yet not been precisely described. We have investigated the contribution of proteases in BM remodeling by localization of transcripts, protein, or enzymatic activity. In addition, we have analyzed BM deposition at the ultrastructural level and by immunofluorescence detection of BM components. At birth, when fragmentation occurred, epithelial cells displayed an upregulation of membrane type 1-matrix metalloproteinase (MT1-MMP) and urokinase-type plasminogen activator (uPA), as well as laminin alpha1 mRNAs. Although MMP2 expression was restricted to mesenchymal cells throughout development, in situ zymography showed that gelatinase-MMP2 activity colocalized with BM deposition inside deepening clefts in the areas of ovigerous cord fragmentation. In the days following birth, gelatin and plasminogen-casein zymography showed an increased enzymatic activity of MMP2 and uPA, respectively. In organotypic cultures of 21-day postconception ovaries, serine protease inhibitors like aprotinin could efficiently block follicle histogenesis. In addition, our results show that the well described and great wave of oocyte attrition characteristic of the days following birth closely correlates with BM remodeling. Altogether, our data show that during follicle histogenesis, ovigerous cord fragmentation results from an acute BM component deposition in deepening clefts and that BM homeostasy involves proteinases of the MMP2/MT1-MMP/TIMP3 and plasminogen/uPA families.
Mazaud
Séverine
S
Laboratoire de Physiologie et Physiopathologie, CNRS-UMR 7079, Université Paris VI, Paris, France.
Guyot
Romain
R
Guigon
Céline J
CJ
Coudouel
Noëlline
N
Le Magueresse-Battistoni
Brigitte
B
Magre
Solange
S
D000818:Animals; D001485:Basement Membrane / Q000196:embryology; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007797:Laminin / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008854:Microscopy, Electron; D009024:Morphogenesis; D006080:Ovarian Follicle / Q000196:embryology* / Q000201:enzymology / Q000648:ultrastructure; D010960:Plasminogen Activators / Q000378:metabolism*; D051381:Rats / Q000196:embryology*
D007797:Laminin; C084098:laminin A; D010960:Plasminogen Activators; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1