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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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Submitted August 30, 2004
Returned for revision September 22, 2004
Accepted December 23, 2004

Pregnancy


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

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

* To whom correspondence should be addressed. E-mail: dmacphee{at}mun.ca.

Abstract
The underlying mechanisms controlling uterine contractions during labour are still poorly understood. Integrins are heterodimeric, transmembrane receptors composed of {alpha} and {beta} subunits that can be found in focal adhesions. Since 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 labour. Itga5 mRNA expression was significantly increased (p<0.05) from day(d) 17 - labour, noticeably decreasing 1 day post -partum (PP). Immunoblot analysis illustrated a continual increase in ITGA5 levels during pregnancy, labour and PP with levels reaching significance at labour (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 on non-pregnant-d6 and in both the longitudinal and circular muscle layers on d15 - PP. Treatment of late pregnant rats with progesterone blocked labour and resulted in sustained expression of Itga5 mRNA expression to d24. In addition, immunocytochemistry experiments showed ITGA5 was detectable at higher levels in cell membranes of both myometrial layers in progesterone-treated animals on d23 and d24, compared to vehicle controls. We propose that ITGA5, with its sole known partner ITGB1, may be important during late pregnancy in promoting cellular cohesion. This process may aid the development of a mechanical syncytium for efficient force transduction during the sustained, coordinated and powerful contractions of labour.

Key words: Female Reproductive Tract • Pregnancy • Parturition • Uterus


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