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BOR - Papers in Press, published online ahead of print January 5, 2005.
Biol Reprod 2005, 10.1095/biolreprod.104.035626
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BIOLOGY OF REPRODUCTION 72, 1114–1124 (2005)
DOI: 10.1095/biolreprod.104.035626
© 2005 by the Society for the Study of Reproduction, Inc.

Expression of {alpha}5 Integrin (Itga5) Is Elevated in the Rat Myometrium During Late Pregnancy and Labor: Implications for Development of a Mechanical Syncytium1

S.J. Williams , B.G. White , and D.J. MacPhee 2 

Division of Basic Medical Sciences, Health Sciences Centre, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3V6

The underlying mechanisms controlling uterine contractions during labor are still poorly understood. Integrins are heterodimeric, transmembrane receptors composed of {alpha} and ß subunits that can be found in focal adhesions. Because these structures play an important role in the regulation of smooth muscle contractility and cell adhesion, we hypothesized that {alpha}5 integrin mRNA (Itga5) and protein (ITGA5) expression would be induced in the rat myometrium during late pregnancy and labor. Itga5 mRNA expression was significantly increased (P < 0.05) from Day 17 to labor, noticeably decreasing 1 day postpartum (PP). Immunoblot analysis illustrated a continual increase in ITGA5 levels during pregnancy, labor, and PP, with levels reaching significance at labor (P < 0.05). Analysis of ITGA5 expression by immunocytochemistry demonstrated that it is primarily localized to myometrial cell membranes in the longitudinal muscle layer of the myometrium from before pregnancy to Day 6, and in both the longitudinal and circular muscle layers from Day 15 to PP. Treatment of late-pregnant rats with progesterone blocked labor and resulted in sustained expression of Itga5 mRNA expression to Day 24. In addition, immunocytochemistry experiments showed ITGA5 was detectable at higher levels in cell membranes of both myometrial layers in progesterone-treated animals on Days 23 and 24, compared with vehicle controls. We propose that ITGA5, with its sole known partner, ITGB1, may be important in promoting cellular cohesion during late pregnancy. This process may aid the development of a mechanical syncytium for efficient force transduction during the sustained, coordinated, and powerful contractions of labor.

female reproductive tract, gene regulation, parturition, pregnancy, uterus


1 Supported by grant 250218-02 from the Natural Sciences and Engineering Research Council of Canada. The experiments described in this manuscript were aided by a New Opportunities Fund infrastructure grant from the Canada Foundation for Innovation (project 74119).

2 Correspondence: Daniel MacPhee, Division of Basic Medical Sciences, Health Sciences Centre, Room 5335, 300 Prince Philip Drive, St. John's, NL, Canada A1B 3V6. FAX: 709 777 7010; dmacphee{at}mun.ca




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