Biomechanisms of cervical remodeling and current approaches to maturity assessment

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The cervical remodeling process is unique and consists of softening, ripening, dilation at fetal birth, and repair to the original state, which is a dense long tubular structure. In this review, the problem of impaired cervical remodeling is discussed in both preterm birth and delayed transformation, which leads to the unpreparedness of the cervix for childbirth and prolongation of pregnancy. Histological, immunological and structural dynamic changes in the cervix begin long before delivery and are noted as early as the first trimester of gestation. There are a few ways to assess the maturity of the cervix. In the second and third trimester, in order to predict preterm birth, these are ultrasound cervicometry and a cervical phosphorylated insulin-like growth factor binding protein-1 test. At full term, in order to determine its readiness for delivery, this is a palpation assessment. Inadequate assessment of the cervical characteristics is one of the factors of untimely prevention of preterm birth, and at full term leads to inappropriate choice of method of preparation for labor. It is necessary to develop new approaches to the comprehensive assessment of the cervix, using existing methods, and to discover new ways to assess its maturity.

In this review, the problem of cervical maturation diagnosis is considered based on literature data from such databases as PubMed, ResearchGate, and Google Scholar, as well as from electronic resources of the M. Gorky Scientific Library (St. Petersburg State University, Russia). This review analyzes data on molecular, biochemical and histophysiological processes occurring during cervical maturation at all stages of gestation.

It is generally accepted that the main role in cervical changes at all stages of gestation is played by: collagen fiber restructuring / desorganization, decreased concentrations of collagen and elastin, high molecular weight hylauronic acid cleavage, increased aquaparin level and tissue hydrophilicity, increased cervical vascularization, as well as changes in glycosaminoglycan and matrix metalloproteinase content. Palpatory technique and ultrasound cervicometry are the most common methods of determining the cervical length, which have insufficient sensitivity, probably because they do not cover all pathogenetic pathways of remodeling and cannot assess all cervical characteristics. Improvement of efficiency is possible through the introduction of combined techniques and the use of promising methods such as elastography, ultrasound diagnosis of the cervix with Doppler assessment of its vessels, determination of a disintegrin and metalloprotease with thrombospondin-like repeats-1 and placental α1-microglobulin in cervical secretion, and relaxin in maternal blood.

Understanding the molecular, biochemical and histophysiological processes that occur during cervical remodeling is crucial for predicting preterm birth, diagnosing isthmic-cervical insufficiency, understanding the lack of timely cervical readiness, and choosing tactics – the method of preinduction and induction of labor if necessary. The lack of clinical methods and their lack of objectivity require a combined approach and the search for new prognostic markers of cervical maturation.

作者简介

Olga Pachuliia

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: for.olga.kosyakova@gmail.com
ORCID iD: 0000-0003-4116-0222
SPIN 代码: 1204-3160
Scopus 作者 ID: 57299197900

MD, Cand. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Vladislava Khalenko

St. Petersburg State University

编辑信件的主要联系方式.
Email: vkhalenko@gmail.com
ORCID iD: 0000-0001-5313-2259
SPIN 代码: 9694-3758
俄罗斯联邦, Saint Petersburg

Margarita Shengeliia

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: bakleicheva@gmail.com
ORCID iD: 0000-0002-0103-8583
SPIN 代码: 7831-2698
Scopus 作者 ID: 57203248029
Researcher ID: AGN-5365-2022
俄罗斯联邦, Saint Petersburg

Olesya Bespalova

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953
SPIN 代码: 4732-8089
Scopus 作者 ID: 57189999252
Researcher ID: D-3880-2018

MD, Dr. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

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2. Fig. 1. Changes in the cervix during pregnancy [3] (transl. by A.V. Mokhnachyov and O.N. Bespalova)

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3. Fig. 2. Changes in the mouse cervical stroma and epithelia during the remodeling process [14]: a, сhanges in the stroma on the 6th and 18th day: the stage of disorganization of the extracellular matrix (transmission electron microscopy of a cross section of mouse cervical collagen fibrils, zoom ×20,500); b, сhanges in the epithelium on the 6th and 18th day: the increased expression of proteins. TFF1 — trefoil factor 1; SPINK5 — serine protease inhibitor Kazal type 5; SRD5a1 — steroid 5 alpha reductase type1; HAS2 — hyaluronan synthase 2; S — stroma; E — epithelium; Os — cervical opening; M — mucus

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4. Fig. 3. Schema of preterm labor [5]: a, morphological structure changes in the cervix during the transition from the softening phase to the maturation phase, characterized by an increase in the number of macrophages; b, changes in the cervix in the transition from the phase of maturation to the phase of opening under the influence of progesterone and paracrine factors (PGs, NO); c, inflammatory and other factors are able to increase the risk of preterm birth when affecting the remodeling processes. PGs — prostaglandins; NO — nitric oxide

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5. Fig. 4. Cervical stroma changes during the remodeling process [14]. a, change of pattern in fibril arrangement and the increase in high molecular weight hyaluronic acid; b, pregnancy: cross-linking between hyaluronic acid and versican; c, late pregnancy, labor: cleavage of cross-links between hyaluronic acid and versican by hyaluronidase and a disintegrin and metalloprotease with thrombospondin-like repeats-1; d, postnatal stage: repair involving neutrophils and macrophages. HA — hyaluronic acid; MW — molecular weight

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