Controlled Fine Needle Biopsy of the Uterine Cervix During Pregnancy

Keeler, Sean; Rust, Orion A.; Kiefer, Daniel; Prutsman, Wendy; Proudfit, Christine; Naftolin, Frederick

doi:10.1177/1933719110396721

Cited by 7 publications

(5 citation statements)

References 27 publications

(58 reference statements)

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“…We showed pregnancy was associated with marked changes in tissue mechanical properties, and these changes correlated with changes in ECM composition [17,18]. However, experiments with human cervical tissue are challenging because it is difficult to obtain sufficient cervical tissue during pregnancy [55]. Animal models, including the mouse, rat, primate, and guinea pig [29,[56][57][58][59][60] have been important for our current understanding of cervical remodeling.…”

Section: House Et Almentioning

confidence: 96%

Inhibitory Effect of Progesterone on Cervical Tissue Formation in a Three-Dimensional Culture System with Human Cervical Fibroblasts1

House

Tadesse-Telila

Norwitz

et al. 2014

Biology of Reproduction

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Progesterone supplementation is recommended to prevent preterm birth in women with a short cervix, but the mechanism is unclear. We hypothesize that progesterone acts by altering the composition of the cervical extracellular matrix (ECM). We tested this hypothesis using human cervical fibroblasts in both two-dimensional (2D) and three-dimensional (3D) cultures. For 2D culture, cells were seeded in 6-well plates and cultured with media supplemented with estradiol (10(-8) M), progesterone (10(-7) or 10(-6) M), and vehicle. For 3D culture, the cells were cultured on a porous silk protein scaffold system. Progesterone and estrogen receptors were documented by immunohistochemistry and Western blot analysis. In both 2D and 3D cultures, decreased collagen synthesis was seen with increased progesterone concentration. Three-dimensional cultures could be maintained significantly longer than 2D cultures, and the morphology of 3D cultures appeared similar to native cervical tissue. Thus, further studies were performed in 3D culture. To determine the effect of progesterone concentration, the 3D scaffolds were cultured with estradiol (10(-8) M) and five conditions: vehicle; 10(-9), 10(-8), or 10(-7) M progesterone; or 10(-7) M progesterone plus 10(-6) M mifepristone. The highest progesterone concentration correlated with the least amount of collagen synthesis. Collagen synthesis progressively increased as progesterone concentration decreased. This effect was partially antagonized by mifepristone, suggesting the mechanism is mediated by the progesterone receptor. This hormonally responsive 3D culture system supports the hypothesis that progesterone has a direct effect on remodeling cervical ECM during pregnancy. The 3D culture system could be useful for studying the mechanism of progesterone effects on the cervix.

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Section: House Et Almentioning

confidence: 96%

Inhibitory Effect of Progesterone on Cervical Tissue Formation in a Three-Dimensional Culture System with Human Cervical Fibroblasts1

House

Tadesse-Telila

Norwitz

et al. 2014

Biology of Reproduction

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“…In considering the role of gonadal steroids in cervical biology and in particular the central role of progesterone in maintaining pregnancy, there is support for the concept that rodents provide a reasonable model for cell biology of the cervix, particularly as it applies to the extracellular matrix [1]. A recent report suggests that tissue-related changes in human subjects may be evaluated through fine needle biopsy of the cervix and that these biopsies were not accompanied by significant risk [7]. Based on this paper, it is likely that many of the observations derived from rodent studies may be verified or replicated in human research participants.…”

Section: Structural and Functional Attributes Of The Cervixmentioning

confidence: 99%

Progesterone Interactions with the Cervix: Translational Implications for Term and Preterm Birth

Larsen

Hwang

2011

Infectious Diseases in Obstetrics and Gynecology

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The uterine cervix plays a vital role in maintaining pregnancy and an equally important role in allowing parturition to occur. Progesterone, either endogenously produced or supplied exogenously, supports the function of the cervix in sustaining intrauterine pregnancy, and the withdrawal of progesterone, either through natural processes or pharmacologic intervention, leads to delivery which underscores the importance of the progesterone's biological activities manifest in normal gestation and pregnancy that ends prematurely. Research crossing many scientific disciplines has demonstrated that progesterone is a pleotropic compound that affects the cervix through cytoplasmic and membrane receptors with profound effects on cellular and molecular functions that influence inflammatory cascades and extracellular matrix, both of which have consequences for parturition. Beyond the local cell and molecular biology of progesterone, it has systemic effects of relevance to pregnancy as well. This paper examines the biology of the cervix from its gross to cellular structure and biological activities of its cell and molecular processes that may be affected by progesterone. The implications of these processes for preterm birth are explored, and direction of current research is in relation to translational medicine implications for diagnostic, prognostic, and therapeutic approaches to threatened preterm birth.

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“…Unfortunately, remodeling is complex. The pregnant cervix undergoes four stages facilitated by differential changes in intertwining layers of aligned collagen: (1) initial softening; (2) shortening and marked softening (‘ripening’); (3) active dilation; and (4) post‐delivery recovery. Biopsies reveal microstructural and histologic changes but invasive exploration is impractical in vivo and results are difficult to interpret because of unrepresentative sampling.…”

Section: Introductionmentioning

confidence: 99%

Estimation of shear wave speed in the human uterine cervix

Carlson

Feltovich

Palmeri

et al. 2014

Ultrasound in Obstet & Gyne

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Objectives Our goals were to explore the spatial variability within the cervix and the sensitivity of shear wave speeds (SWS) to assess softness/stiffness differences in ripened (softened) versus unripened tissue. Methods We obtained SWS estimates from hysterectomy specimens (n=22), a subset of which were ripened (n = 13). Multiple measurements were made longitudinally along the cervical canal on both the anterior and posterior sides of the cervix. Statistical tests of differences in the proximal vs. distal, anterior vs. posterior, and ripened vs. unripened cervix were performed with individual two-sample t-tests and a linear mixed model. Results We discovered that SWS estimates monotonically increase from distal to proximal longitudinally along the cervix, that they also vary in the anterior compared to the posterior cervix, and that they are significantly different in ripened vs. unripened cervical tissue. Specifically, the mid position SWS estimates for the unripened group were 3.45±0.95 m/s (anterior) and 3.56±0.92 m/s (posterior), and 2.11±0.45 m/s (anterior) and 2.68±0.57 m/s (posterior) for the ripened (p<0.001). Conclusions We propose that shear wave speed estimation may be a valuable research and, ultimately, diagnostic tool for objective quantification of cervical stiffness/softness.

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Controlled Fine Needle Biopsy of the Uterine Cervix During Pregnancy

Abstract: FNB of the cervix in high risk gravidae is feasible in clinical situations. It did not increase the risk of adverse events compared to women studied under a similar protocol without FNB.

Cited by 7 publications

References 27 publications

Inhibitory Effect of Progesterone on Cervical Tissue Formation in a Three-Dimensional Culture System with Human Cervical Fibroblasts1

Inhibitory Effect of Progesterone on Cervical Tissue Formation in a Three-Dimensional Culture System with Human Cervical Fibroblasts1

Progesterone Interactions with the Cervix: Translational Implications for Term and Preterm Birth

Estimation of shear wave speed in the human uterine cervix

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