Cervical remodeling during pregnancy and parturition

Abstract

Appropriate and timely cervical remodeling is key for successful birth. Premature cervical opening can result in preterm birth which occurs in 12.5% of pregnancies. Research focused on the mechanisms of term and preterm cervical remodeling is essential to prevent prematurity. This review highlights recent findings that better define molecular processes driving progressive disorganization of the cervical extracellular matrix. This includes studies that redefine the role of immune cells and identify diverse functions of the cervical epithelia and hyaluronan in remodeling. New investigations proposing that infection-induced premature cervical remodeling is distinct from the normal process are presented. Recent advances in our understanding of term and preterm cervical remodeling provide new directions for investigation and compel investigators to reevaluate currently accepted models. OverviewThe transformation of the cervix from a closed rigid structure to one that opens sufficiently for birth is an active dynamic process that begins long before the onset of labor. Better understanding of the molecular process of cervical remodeling is critical for the development of therapies to treat preterm birth and postterm pregnancies due to cervical malfunction. In this review, recent insights gained from studies in rodent models will be presented and contrasted with human studies. Although the mechanisms used to achieve the appropriate hormonal environment for each phase of cervical remodeling differ between human and rodent (Box 1), the end result is a similar endocrine environment; further, there is a growing body of evidence that molecular mechanisms of cervical remodeling are well conserved between these two species. This review highlights some of the recent findings in this area. Distinct phases of remodelingCervical remodeling can be loosely divided into four distinct but overlapping phases termed softening, ripening, dilation and postpartum repair (Table 1) [1,2]. Softening can be defined as the first measurable decline in the tensile strength or tissue compliance compared to nonpregnancy. Biomechanical studies in mice or digital exam in women indicate softening begins by day 12 of a 19 day gestation in mice and in the first trimester of pregnancy in women [1,3]. This phase is unique from the subsequent two phases in that softening is a relatively slow and incremental process taking place in a progesterone rich environment. Despite the progressive increase in compliance, tissue competence is maintained. Following softening, cervical ripening is a more accelerated phase characterized by maximal loss of tissue © 2010 Elsevier Ltd. All rights reservedCorresponding author: Mahendroo, M (mala.mahendroo@utsouthwestern.edu). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is p...

Vascular endothelial growth factor induces mRNA expression of pro-inflammatory factors in the uterine cervix of mice

“…Other evidence is from studies using mice deficient in receptors for classical inflammatory factors, such as interleukin (IL)-1α and tumor necrosis factor (TNF)-α, or those showing that mice treated with blockers of these receptors are more resistant to the toll-like receptor agonist (lipopolysaccharide, LPS)-induced preterm birth (14,15). It is important to note that the association of inflammation in normal uterine cervical remodeling and birth has recently been disputed by some studies (5,40,41). For instance, it has been shown that pharmacological depletion of inflammatory cells in the uterine cervix does not block cervical remodeling or parturition, and that although there is increased tissue infiltration by immune cells in late pregnancy, immune cells are not activated until after birth (40).…”

Cervical remodeling in term and preterm birth: insights from an animal model

“…1). Evaluation of collagen fiber structure by SHG microscopy reveals progressive changes in the morphological features of collagen type I fibers over the course of pregnancy (Akins et al 2010). Most notable in SHG images is the transition from long thin collagen fibers to thicker curved fibers at term.…”

“…There is potential for differences in epithelial cell function between species as the human cervix is composed of glandular epithelia and a columnar and squamous epithelia that line the endocervix and ectocervix, respectively, while the mouse does not have glandular epithelia and the endocervix and ectocervix is primarily composed of squamous epithelia with a small region of columnar epithelia in the endocervix. Given the recent appreciation of the important roles of epithelia in the maintenance of barrier properties and immune surveillance in mouse and human, a better understanding of these differences is needed (Timmons et al 2010, Nold et al 2012.…”

Human Papillomavirus: Biology and Pathogenesis

“…The HR-HPVs have the ability to infect several types of epithelial cells, but they can cause cancer more frequently in the uterine cervix (Timmons et al, 2010). The cervical cancer arises preferentially in the cervical transformation zone (TZ), located in the boundary between the squamous epithelium of ectocervix and the columnar epithelium of endocervix.…”