HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 77/5/880    most recent biolreprod.107.062356v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shynlova, O. Articles by Lye, S. J Search for Related Content PubMed PubMed Citation Articles by Shynlova, O. Articles by Lye, S. J Agricola Articles by Shynlova, O. Articles by Lye, S. J

Uterine Stretch Regulates Temporal and Spatial Expression of Fibronectin Protein and Its Alpha 5 Integrin Receptor in Myometrium of Unilaterally Pregnant Rats¹

Division of BioMedical Sciences,⁷ Health Science Centre, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3V6 Samuel Lunenfeld Research Institute,⁴ Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 Departments of Physiology,⁵ and Obstetrics & Gynecology,⁶ University of Toronto, Toronto, Ontario, Canada M5S 1A1

ABSTRACT

The adaptive growth of the uterus during pregnancy is a critical event that involves increased synthesis of extracellular matrix (ECM) proteins and dynamic remodeling of smooth muscle cell (SMC)-ECM interactions. We have previously found a dramatic increase in the expression of the mRNAs that encode fibronectin (FN) and its alpha5-integrin receptor (ITGA5) in pregnant rat myometrium near to term. Since the myometrium at term is exposed to considerable mechanical stretching of the uterine wall by the growing fetus(es), the objective of the present study was to examine its role in the regulation of FN and ITGA5 expression at late gestation and during labor. Using myometrial tissues from unilaterally pregnant rats, we investigated the temporal changes in Itga5 gene expression in gravid and empty uterine horns by Northern blotting and real-time PCR, in combination with immunoblotting and immunofluorescence analyses of the temporal/spatial distributions of the FN and ITGA5 proteins. In addition, we studied the effects of early progesterone (P4) withdrawal on Itga5 mRNA levels and ITGA5 protein detection. At all time-points examined, the Itga5 mRNA levels were increased in the gravid uterine horn, compared to the empty horn (P < 0.05). Immunoblot analysis confirmed higher ITGA5 and FN protein levels in the myometrium, associated with gravidity (P < 0.05). Immunodetection of ITGA5 was consistently high in the longitudinal muscle layer, increased with gestational age in the circular muscle layer of the gravid horn, and remained low in the empty horn. ITGA5 and FN immunostaining in the gravid horn exhibited a continuous layer of variable thickness associated directly with the surfaces of individual SMCs. In contrast to the effects of stretch, P4 does not appear to regulate ITGA5 expression. We speculate that the reinforcement of the FN-ITGA5 interaction: 1) contributes to myometrial hypertrophy and remodeling during late pregnancy; and 2) facilitates force transduction during the contractions of labor by anchoring hypertrophied SMCs to the uterine ECM.

cellular cohesion, pregnancy, progesterone, uterus

³These authors contributed equally to this work.

¹Supported by CIHR (S.J.L.) and NSERC (D.J.M.).

Correspondence: ²Stephen J. Lye, Samuel Lunenfeld Research Institute at Mount Sinai, 600 University Avenue, Suite 870, Toronto, ON, Canada M5G 1X5. FAX: 416 586 8587; e-mail: lye{at}mshri.on.ca