Anti-inflammatory effect of proteoglycan and progesterone on human uterine cervical fibroblasts

Fukuyama, Asami; Kakizaki, Ikuko; Kasai, Kosuke; Chiba, Mitsuru; Nakamura, Toshiya; Mizunuma, Hideki

doi:10.1016/j.lfs.2011.12.024

Cited by 26 publications

(19 citation statements)

References 42 publications

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“…This is not to discount the potential role for an inflammatory response and cervical remodeling. Indeed, crosstalk between cervical fibroblasts and the immune system has been demonstrated [36,[61][62][63][64][65]. Rather, this study supports the hypothesis that multiple pathways are important for preparing the cervix for parturition [66].…”

Section: Three-dimensional Culture Of Cervical Fibroblastssupporting

confidence: 62%

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: Three-dimensional Culture Of Cervical Fibroblastssupporting

confidence: 62%

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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“…10,11 In contrast, levonorgestrel-releasing IUDs cause downregulation of sex steroid receptors as well as suppression of cervical and uterine local immunity through decreased prostaglandin production. 12,13 We hypothesize that chronic inflammation induced by the copper-containing IUD may promote spontaneous clearance of high-risk HPV infection, whereas the antiinflammatory properties of a levonorgestrel-containing IUD may promote persistence. We sought to compare proportions of persistent high-risk HPV infection and abnormal cytology between women using copper-and levonorgestrel-containing IUDs.…”

Section: Level Of Evidence: IImentioning

confidence: 99%

Comparison of Human Papillomavirus Infection and Cervical Cytology in Women Using Copper-Containing and Levonorgestrel-Containing Intrauterine Devices

Lekovich

Amrane

Pangasa

et al. 2015

Obstetrics &Amp; Gynecology

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“…Progestogens have been shown to reduce the incidence of candidal vaginitis and bacterial vaginosis . Additionally, progestogens have been shown to have antibacterial functions, can inhibit the growth the Neisseria gonorrhea , and can alter the gastric mucosal response to impair the viability of Helicobacter pylori . Similar factors may be at play in reducing local GBS colonisation when progesterone is applied vaginally.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 The literature on whether progestogens have an effect on the vaginal microbiome is conflicting. [17][18][19][20][21] Progesterone has known antibacterial, immunomodulatory, and anti-inflammatory properties, [22][23][24] with demonstrated effects on dendritic cells, macrophages, T-cells, B-cells, and cytokine release. [25][26][27][28][29][30][31] Animal models have demonstrated that intravaginal progesterone has local anti-inflammatory effects at the maternalfetal interface and the cervix.…”

Section: Introductionmentioning

confidence: 99%

Vaginal progesterone is associated with decreased group B streptococcus colonisation at term: a retrospective cohort study

Ma’ayeh

Rood

Walker

et al. 2019

BJOG

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Objective To investigate whether women using intravaginal progesterone suppositories for preterm birth prevention during pregnancy will have lower rates of group B streptococcus (GBS) colonisation at term, compared with women receiving intramuscular 17‐alpha‐hydroxyprogesterone caproate. Design This was a retrospective observational cohort study of women who were prescribed a progestogen during their pregnancy for preterm birth prevention, and who delivered at term. Setting A tertiary referral hospital in central Ohio. Population Patients who were prescribed a progestogen during their pregnancy for preterm birth prevention between 2004 and 2017 were included in the study. Patients who delivered at <37 weeks of pregnancy, switched progestogen type during the pregnancy, or had a pessary or cerclage placed were excluded. Methods Baseline characteristics were compared using Mann–Whitney U‐test or Chi‐square test as appropriate. The association between type of progestogen and GBS colonisation was assessed using bivariate and multivariable analyses. Main outcome measures The primary outcome was GBS colonisation. Results In all, 565 patients were included in the study, of whom 173 received intravaginal progesterone, and 392 17‐alpha‐hydroxyprogesterone caproate. Patients receiving intravaginal progesterone were less likely to be colonised with GBS (19.7 versus 28.1%). After adjustments for potential confounders were made in a multivariable logistic regression analysis, receiving intravaginal progesterone suppositories (adjusted odds ratio [OR] 0.61, 95% CI 0.39–0.95) was associated with reduced GBS colonisation. Conclusions Intravaginal progesterone is associated with a decreased prevalence of rectovaginal GBS colonisation at term. Tweetable abstract Vaginal progesterone is associated with a lower incidence of rectovaginal GBS colonisation, compared with 17α‐hydroxyprogesterone caproate.

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Anti-inflammatory effect of proteoglycan and progesterone on human uterine cervical fibroblasts

Cited by 26 publications

References 42 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

Comparison of Human Papillomavirus Infection and Cervical Cytology in Women Using Copper-Containing and Levonorgestrel-Containing Intrauterine Devices

Vaginal progesterone is associated with decreased group B streptococcus colonisation at term: a retrospective cohort study

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