American Journal of Obstetrics and Gynecology
Original ResearchObstetricsA new paradigm for the role of smooth muscle cells in the human cervix
Introduction
Spontaneous preterm birth (sPTB) is a significant obstetric dilemma affecting approximately 10% of US pregnancies.1, 2 Etiologies vary, but sPTB must eventually involve premature remodeling and dilation of the cervix to allow for delivery of the premature fetus.3 Although the pathophysiology of premature cervical remodeling is not fully understood, sonographic findings and computational modeling suggest that in some cases, the process starts with dilation of the internal os (the top aspect of the cervix where the uterine arteries insert into the uterus), which is clinically termed “funneling”4, 5 (Figure 1). Clinicians also describe a “dynamic cervix” where the cervix appears shortened in the absence of uterine contractions, which can be seen if transvaginal ultrasound is performed for several minutes. A dynamic cervix has also been described as cervical shortening in response to fundal pressure. Despite these clinical findings, we still cannot explain why the internal os weakens first in some cases of premature cervical remodeling. Our overall goal is to study whether premature cervical failure at the level of the internal os is due to regional differences in cervical tissue morphology and function.
Since the 1940s, the cervix has been characterized as a mostly collagenous structure (90% collagen/extracellular matrix [ECM]) with minimal cellular content (10% smooth muscle cells [SMC]).6, 7, 8 However, these early studies suffered from technical limitations of the time and used immunohistochemical methods (Masson trichrome staining and subjective evaluation of SMC morphology)6, 7, 8 that do not specifically identify SMC. Decades later, investigators questioned why SMC exist in the cervix. Interestingly, Bryman et al9, 10, 11 found that adrenoreceptor agonists and oxytocin stimulate human tissue from the external os (lowermost aspect of the cervix closest to the vagina) to contract, suggesting SMC play a role in cervical tissue contractility.
Since the turn of this century, however, cervical SMC (CSMC) have been largely ignored since CSMC content was thought to be minimal. Instead, researchers focused on identifying alterations in the human cervical collagen network to explain premature cervical failure.12, 13, 14, 15, 16, 17 Since clinical observation demonstrates the area of the internal os can funnel first and/or is dynamic in some cases of premature cervical remodeling, we believe that the working paradigm of cervical tissue architecture needs to be reevaluated. Here, we use improved immunohistochemical techniques and functional studies to determine if regional differences in CSMC content and distribution influence cervical tissue function. The knowledge from this study will expand our understanding of cervical tissue characteristics that may contribute to normal and abnormal cervical function in pregnancy.
Section snippets
Tissue collection
This study was approved by the institutional review board at Columbia University Medical Center and Intermountain Healthcare. Nonpregnant, premenopausal women (<50 years old) undergoing a total hysterectomy for benign indications were consented. Women with an abnormal pap smear or prior cervical surgery were excluded. Demographic data (age, parity, obstetric history, menstrual phase, body mass index, and race) were collected.
Evaluation of CSMC at the internal and external os
Immediately following hysterectomy, whole transverse slices (3-mm
Evaluation of CSMC at the internal and external os
In some women with premature cervical failure, the internal os dilates first while the external os remains closed. To understand how cervical tissue structure influences its function, our initial goal was to understand general cervical tissue composition at the internal and external os using a Movat pentachrome stain, which allows for simultaneous visualization of collagen, mucin, and muscle. Whole transverse slices from the internal and external os were obtained from 13 nonpregnant women (5
Comment
The findings from this study suggest a revised paradigm of SMC organization and function in the human cervix (Figure 11). Unlike the prevailing paradigm that states the cervix is mainly collagen/ECM with minimal cellular content, our revised paradigm shows that the area of the internal os, the area that “fails” or “funnels” first in some cases of premature cervical remodeling, contains 50-60% CSMC and bundles of CSMC can be found circumferentially oriented around the periphery of the cervix.
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Supported by a Society for Maternal-Fetal Medicine Foundation/American Association of Obstetricians and Gynecologists Foundation Scholarship. This foundation had no role in the study design, tissue collection, or analysis and interpretation of the data. Images were collected in the Confocal and Specialized Microscopy Shared Resource of the Herbert Irving Comprehensive Cancer Center at Columbia University, supported by National Institutes of Health grant no. P30 CA013696 (National Cancer Institute).
The authors report no conflict of interest.
Cite this article as: Vink JY, Qin S, Brock CO, et al. A new paradigm for the role of smooth muscle cells in the human cervix. Am J Obstet Gynecol 2016;215:478.e1-11.