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

Mahendroo, Mala

doi:10.1530/rep-11-0466

Cited by 170 publications

(156 citation statements)

References 70 publications

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“…The current review has focused on events and potential mechanisms of parturition that are detectable in systemic steroid concentrations, such as progestin withdrawal itself, but changes at the tissue and cellular level will no doubt help to explain phenomena induced locally to differing degrees among species. These might include expression of different forms of the PR that are antagonistic [187][188][189][190], local metabolism of progesterone [54,191,192], and/or direct effects progesterone or DHP metabolites (neurosteroids) on myometrium and other excitable membranes [54] that are not mediated through the PR [193]. These may be less important in species, such as the horse where progestin withdrawal is signaled by decreasing concentrations of pregnanes in the maternal circulation a few days before delivery [195].…”

Section: The Initiation Of Parturitionmentioning

confidence: 99%

Review of the reproductive endocrinology of the pregnant and parturient mare

Conley

2016

Theriogenology

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Section: The Initiation Of Parturitionmentioning

confidence: 99%

Review of the reproductive endocrinology of the pregnant and parturient mare

Conley

2016

Theriogenology

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“…Animal studies reveal rearrangement of collagen structure is achieved in part by a decline in collagen crosslink formation, a reduction in matricellular proteins that regulate collagen fibrillogenesis, and increased synthesis of the matrix disorganizing molecule, hyaluronan (3,4). Evidence to support a conservation of these processes in cervical remodeling in women is mounting (5). Abnormal or inappropriately timed cervical remodeling can lead to premature birth.…”

mentioning

confidence: 99%

A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy

Zhang

Akins²,

Murari

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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We report the development of an all-fiber-optic scanning endomicroscope capable of high-resolution second harmonic generation (SHG) imaging of biological tissues and demonstrate its utility for monitoring the remodeling of cervical collagen during gestation in mice. The endomicroscope has an overall 2.0 mm diameter and consists of a single customized double-clad fiber, a compact rapid two-dimensional beam scanner, and a miniature compound objective lens for excitation beam delivery, scanning, focusing, and efficient SHG signal collection. Endomicroscopic SHG images of murine cervical tissue sections at different stages of normal pregnancy reveal progressive, quantifiable changes in cervical collagen morphology with resolution similar to that of bench-top SHG microscopy. SHG endomicroscopic imaging of ex vivo murine and human cervical tissues through intact epithelium has also been performed. Our findings demonstrate the feasibility of SHG endomicroscopy technology for staging normal pregnancy, and suggest its potential application as a minimally invasive tool for clinical assessment of abnormal cervical remodeling associated with preterm birth.nonlinear endomicroscopy | fiber-optic scanning probe | cervical collagen remodeling | parturition T he cervix is a connective tissue-rich structure just caudal to the uterus in female mammals. Appropriate remodeling of the cervix during gestation is an essential component of the birth process (1, 2). The cervix must remain closed during pregnancy to maintain the fetus in the womb, and then open sufficiently to allow passage of the fetus at term. This shift in responsibility requires a massive rearrangement of the cervical connective tissue, in particular fibrillar collagen. Collagen is the main structural protein in the cervix. Animal studies reveal rearrangement of collagen structure is achieved in part by a decline in collagen crosslink formation, a reduction in matricellular proteins that regulate collagen fibrillogenesis, and increased synthesis of the matrix disorganizing molecule, hyaluronan (3, 4). Evidence to support a conservation of these processes in cervical remodeling in women is mounting (5). Abnormal or inappropriately timed cervical remodeling can lead to premature birth.Preterm birth (PTB), which accounts for 12.7% of all births in the United States, is the second leading cause of infant mortality and often leads to serious morbidity in surviving infants (6). Despite considerable research, the cause of PTB in 50% of cases remains elusive, and diagnostic methods to detect women at risk of PTB are limited (7). Because clinical and animal studies suggest that cervical changes precede the onset of uterine contractility in both term and PTB, premature cervical changes could be indicative of impending PTB (4, 8-10). The progressive structural changes in fibrillar collagens are directly related to cervical rigidity and thus potentially can serve as a diagnostic indicator for women at risk for PTB.Second harmonic generation (SHG) microscopy is the most effective ...

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“…Il-1, IL-8 and CCL-2) (14,15). Progesterone also inhibits TNF-α-induced apoptosis and matrix metalloproteinases-induced cervical ripening (16)(17)(18)(19). If progesterone levels are altered however, these protective mechanisms are reversed and labour ensues (7).…”

Section: Aetiology and Risk Factors For Ptbmentioning

confidence: 99%

“…Progesterone may reduce PTB, probably due to its effects in controlling cervical ripening (11,16). However, evidence surrounding its efficacy and potential long-term consequences are conflicting.…”

Section: Progesteronementioning

confidence: 99%

The Role of PTB Clinics: A Review of the Screening Methods, Interventions and Evidence for Preterm Birth Surveillance Clinics for High-Risk Asymptomatic Women

et al. 2017

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Context: Preterm birth accounts for significant neonatal mortality and morbidity as well as substantial health costs. As our understanding of aetiology and risk factors for preterm birth increases, predictive tools and prophylactic interventions have been developed to improve maternal and fetal outcomes. These are effective, but require surveillance of asymptomatic high-risk women, as well as ultrasound and surgical expertise. This has led to the development of preterm birth surveillance clinics (PSCs), which pool these resources together and have changed the focus of care from reactive to predictive and preventative management. Methods: A literature review of the evidence surrounding the predictive tests (cervical length, fetal fibronectin, Actim Partus, Partosure) and prophylactic interventions (cerclage, progesterone, Arabin pessary, antibiotics, and steroids) for preterm birth to understand what preterm birth surveillance clinics do and how effective they are. Results: Measuring cervical length and fetal fibronectin levels are two of the most accurate predictive tests preterm birth, especially when used in combination. Other predictive tools like Actim Partus and Partosure are effective for symptomatic women, but their role in surveillance of asymptomatic women is unclear. Cervical cerclage is effective in reducing preterm birth in women with previous losses, but the role of progesterone and pessaries remains debated. Steroids remain one of the most effective antenatal intervention, but they need to be administered within a tight timeframe in order to confer maximal benefit. The role of PSCs in predicting the timing of birth and targeting women at highest risk to appropriate interventions is therefore crucial in optimizing care and improving outcomes. Conclusions: Nearly every step of management is still debated although many have a strong evidence-base and effective interventions do exist. The challenge is finding the optimal management pathway, and details of which populations benefit from which interventions need to be evaluated. While evidence continues to be collated, the poor outcomes of preterm birth and the multiple options available to reduce them justify preterm birth surveillance clinics being resourced.Keywords: Preterm Birth, Predictive, Fetal Fibronectin, Cervical Length, Cervical Cerclage ContextDefined as spontaneous or induced birth before 37+ 0 weeks' gestation, preterm birth (PTB) is responsible for significant perinatal morbidity and mortality. Preterm labour affects 11.1% of live births worldwide (1) and 7.6% of live births in England and Wales (2), but incidence is rising globally (3). PTB causes more than 3 million perinatal deaths a year (1) and causes increased risks of neurodevelopmental impairment, behavioural problems and respiratory diseases, which constitute significant health costs and decreased quality of life (4-6). MethodsThe primary research question our review is addressing is "what predictive tests and prophylactic interventions to preterm birth surveillance clini...

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

Cited by 170 publications

References 70 publications

Review of the reproductive endocrinology of the pregnant and parturient mare

Review of the reproductive endocrinology of the pregnant and parturient mare

A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy

The Role of PTB Clinics: A Review of the Screening Methods, Interventions and Evidence for Preterm Birth Surveillance Clinics for High-Risk Asymptomatic Women

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