Progesterone and Gravidity Differentially Regulate Expression of Extracellular Matrix Components in the Pregnant Rat Myometrium1

Dec 3, 2003Biology of reproduction

Progesterone and pregnancy history differently influence support tissue proteins in the pregnant rat uterus

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Abstract

Expression of fibronectin, laminin beta2, and collagen IV mRNA significantly increased on Day 23 during labor.

Myometrial tissue showed low levels of fibronectin, laminin beta2, and collagen IV mRNA during early gestation, which rose dramatically at labor onset.
Fibrillar collagens (type I and III) peaked in expression on Day 19 and declined as pregnancy approached term.
Elastin mRNA levels remained elevated from midgestation through labor.
Maintaining elevated progesterone levels delayed labor and reduced fibronectin and laminin mRNA levels while preventing the drop in collagen III mRNA on Day 23.
Administering a progesterone receptor antagonist induced preterm labor and prematurely increased mRNA levels of collagen IV, fibronectin, and laminin.
Changes in extracellular matrix gene expression were primarily localized to the gravid horn of unilaterally pregnant rats.

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Myometrial growth and remodeling during pregnancy depends on increased synthesis of interstitial matrix proteins. We hypothesize that the presence of mechanical tension in a specific hormonal environment regulates the expression of extracellular matrix (ECM) components in the uterus. Myometrial tissue was collected from pregnant rats on Gestational Days 0, 12, 15, 17, 19, 21, 22, 23 (labor), and 1 day postpartum and ECM expression was analyzed by Northern blotting. Expression of fibronectin, laminin beta2, and collagen IV mRNA was low during early gestation but increased dramatically on Day 23 during labor. Expression of fibrillar collagens (type I and III) peaked Day 19 and decreased near term. In contrast, elastin mRNA remained elevated from midgestation onward. Injection of progesterone (P4) on Days 20-23 (to maintain elevated plasma P4 levels) delayed the onset of labor, caused dramatic reductions in the levels of fibronectin and laminin mRNA, and prevented the fall of collagen III mRNA levels on Day 23. Treatment of pregnant rats with the progesterone receptor antagonist RU486 on Day 19 induced preterm labor on Day 20 and a premature increase in mRNA levels of collagen IV, fibronectin, and laminin. Analysis of the uterine tissue from unilaterally pregnant rats revealed that most of the changes in ECM gene expression occurred specifically in the gravid horn. Our results show a decrease in expression of fibrillar collagens and a coordinated temporal increase in expression of components of the basement membrane near term associated with decreased P4 and increased mechanical tension. These ECM changes contribute to myometrial growth and remodeling during late pregnancy and the preparation for the synchronized contractions of labor.

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Progesterone and Gravidity Differentially Regulate Expression of Extracellular Matrix Components in the Pregnant Rat Myometrium1

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