In which of the following uterine walls is the powerful muscular layer that contracts during childbirth?

Journal Article

Hector N. Aguilar,

1

Department of Physiology

,

University of Alberta

,

Edmonton, Alberta

,

Canada

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Received:

31 October 2009

Revision received:

29 April 2010

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  Hector N. Aguilar, B.F. Mitchell, Physiological pathways and molecular mechanisms regulating uterine contractility, Human Reproduction Update, Volume 16, Issue 6, November-December 2010, Pages 725–744, //doi.org/10.1093/humupd/dmq016

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Abstract

Introduction

The uterus is a hollow organ with a well-differentiated lining layer [endometrium], a thick muscular coat [myometrium] and a serosal outer layer. There has been remarkable progress towards understanding the physiology and clinical pathophysiology of the endometrium and this has resulted in many important interventions to affect conception and contraception as well as menstrual function. In contrast, although there is growing awareness of the potential importance of abnormal function of the uterine muscle layer, there has been relatively little research concerning the role of the myometrium in common disorders of reproduction. Myometrial function may be of vital importance in physiological processes such as sperm and embryo transport and implantation, and in disorders such as dysmenorrhea and endometriosis. At present there is limited understanding of regulation of uterine contractility in the non-pregnant state. Yet, better understanding of this physiology is essential to design and test interventions that can prevent or treat the important clinical problems noted above. To fill in the gaps in our knowledge of uterine physiology in the non-pregnant state, we shall borrow liberally from knowledge gained from experiments using both human and animal models, whether pregnant or not. The goal of this review is to provide an overview of the molecular mechanisms that might regulate uterine contractility, particularly emphasizing recent findings with potential clinical applicability to improvement of reproductive health.

Methods

The initial search strategy involved searching the United States National Library of Medicine [//www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed] and matching ‘uterus’ or ‘uterine myocyte’ with ‘calcium signaling’, ‘myosin light chain kinase [MLCK]’, ‘ myosin light chain phosphatase [MLCP]’ or ‘calcium sensitization’. Papers were selected based on the relevance to our objectives as determined by review of the titles and abstracts. After synthesizing a review of this information, key references obtained from these papers were individually reviewed and selected based on their potential relevance to uterine smooth muscle [SM]. This information was used to expand the discussion of the regulation of uterine SM. The term ‘uterine contractility’ then was entered and articles were selected based on their clinical relevance to disorders of reproduction in non-pregnant women. Finally, the review was edited and shortened to focus on molecular mechanisms regulating contractility of the non-pregnant uterus with emphasis on information that could be clinically applicable for the improvement of reproductive health.

The contractile apparatus

Anatomical considerations and uterine contractile activity

Uterine contractions occur throughout the menstrual cycle in the non-pregnant state and throughout gestation. There are four important parameters that change under various physiological or pathophysiological conditions: frequency, amplitude, duration and direction of propagation. Over the past two decades, considerable information regarding myometrial function in non-pregnant women has been obtained from the use of open-tipped pressure catheter recordings or from three-dimensional ultrasound or magnetic resonance imaging [MRI]. Several reviews have described these changes and their potential clinical significance [Brosens et al., 1998; van Gestel et al., 2003; Bulletti et al., 2004; Bulletti and de Ziegler, 2006]. Contractile activity in the non-pregnant uterus appears to be fundamentally different than in the pregnant organ. The contractions observed during the menstrual cycle have been termed ‘endometrial waves’ [Ijland et al., 1996]. Using a variety of imaging techniques, these contractions appear to involve only the sub-endometrial layer of the myometrium. These observations have led to a new concept of uterine anatomy that encompasses two distinct zones of the myometrium [Fig. 1].

Figure 1

Concept of the sub-endometrial layer of myometrium. This thinner, innermost layer of muscle fibers, which are arranged predominantly in a circular configuration around the uterine cavity, is suggested to be of different embryological origin with physiological properties distinct from the more prominent outer layer. The circular sub-endometrial layer may facilitate the changing vectors of ‘endometrial waves’ that might play important roles in common reproductive disorders. The outer layer is likely to be more important in more intense uterine activity including abortion or parturition.

In the early follicular phase following menstruation, contractile waves occur once or twice per minute and last 10–15 s with low-amplitude [usually