Evolution of Gene Expression in the Uterine Cervix related to Steroid Signaling: Conserved features in the regulation of cervical ripening

Wagner, Günter P.; Nnamani, Mauris C.; Chavan, Arun R.; Maziarz, Jamie; Protopapas, Stella; Condon, Jennifer C.; Romero, Roberto

doi:10.1038/s41598-017-04759-6

Cited by 11 publications

(11 citation statements)

References 57 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To test this hypothesis, we measured uterine expression of Fkbp5 and Fkbp4, Pgr and P4 metabolizing enzymes Akr1c18 and Srd5a1 (5α-reductase, which metabolizes P4 to 5α-pregnane-3,20-dione and is primarily expressed in mouse cervix but also in the uterus) (40,41). Consistent with our findings in human decidua ( Fig.…”

Section: Of 12 | Pnassupporting

confidence: 78%

Decidual cell FKBP51–progesterone receptor binding mediates maternal stress–induced preterm birth

Guzeloglu‐Kayisli

Semerci

Guo

et al. 2021

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

View full text Add to dashboard Cite

Depression and posttraumatic stress disorder increase the risk of idiopathic preterm birth (iPTB); however, the exact molecular mechanism is unknown. Depression and stress-related disorders are linked to increased FK506-binding protein 51 (FKBP51) expression levels in the brain and/or FKBP5 gene polymorphisms. Fkbp5-deficient (Fkbp5−/−) mice resist stress-induced depressive and anxiety-like behaviors. FKBP51 binding to progesterone (P4) receptors (PRs) inhibits PR function. Moreover, reduced PR activity and/or expression stimulates human labor. We report enhanced in situ FKBP51 expression and increased nuclear FKBP51-PR binding in decidual cells of women with iPTB versus gestational age-matched controls. In Fkbp5+/+ mice, maternal restraint stress did not accelerate systemic P4 withdrawal but increased Fkbp5, decreased PR, and elevated AKR1C18 expression in uteri at E17.25 followed by reduced P4 levels and increased oxytocin receptor (Oxtr) expression at 18.25 in uteri resulting in PTB. These changes correlate with inhibition of uterine PR function by maternal stress–induced FKBP51. In contrast, Fkbp5−/− mice exhibit prolonged gestation and are completely resistant to maternal stress–induced PTB and labor-inducing uterine changes detected in stressed Fkbp5+/+ mice. Collectively, these results uncover a functional P4 withdrawal mechanism mediated by maternal stress–induced enhanced uterine FKBP51 expression and FKPB51-PR binding, resulting in iPTB.

show abstract

Section: Of 12 | Pnassupporting

confidence: 78%

Decidual cell FKBP51–progesterone receptor binding mediates maternal stress–induced preterm birth

Guzeloglu‐Kayisli

Semerci

Guo

et al. 2021

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

View full text Add to dashboard Cite

show abstract

“…Since circRNAs can activate the transcription of their parental genes, the function of these genes could indirectly reflect the biological impact of circRNAs to some extent (Fischer and Leung, 2017). Among all parental genes of selected circRNAs, CREBBP (the gene of hsa-CREBBP_0001) has been noted to affect the inflammatory signal (NF-κB pathway) of the myometrium, and closely related to labor onset and PTB (Zeng et al, 2008;Wagner et al, 2017). Thus, hsa-CREBBP_0001 was suggested to be associated with PTB by affecting the inflammatory pathway.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of Circular RNA as a Novel Regulator and Biomarker in Preterm Birth

Ran

Yin

Huang

et al. 2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Preterm birth (PTB), as the leading cause of neonatal death, is a severe threat to maternal–fetal health. The diagnosis and treatment of PTB are difficult as its underlying mechanism still unknown. Circular RNA (circRNA) is an emerging molecule that plays an essential role in the pathological processes of various diseases. However, it is still unclear whether circRNAs are abnormal or involves in the PTB pathology. In this study, we analyzed RNA-seq data of peripheral blood from preterm and term pregnant women and verified with microarray data. There were 211 circRNA expression disorders in PTB, of which 68 increased and 143 decreased. Bioinformatics analysis revealed that the top 20 circRNAs competitively bind 68 miRNAs, thereby regulating 622 mRNAs mainly related to immunity, inflammation, and nerve activity, which may ultimately contribute to the occurrence of PTB. Moreover, 6 regulatory pairs, including hsa-MORC3_0001–hsa-miR-1248–CHRM2 were the core parts of this mechanism network, which might be therapeutic targets for PTB. Besides, ROC analysis indicated that hsa-ANKFY1_0025, hsa-FAM13B_0019, and hsa-NUSAP1_0010 (AUC = 0.7138, 0.9589, 1.000) have an excellent discrimination ability for PTB. Taken together, we explored for the first time the circRNA expression profile of PTB, and preliminarily analyzed its regulatory mechanism and predictive value for PTB, thus bringing new light to the diagnosis and treatment of PTB.

show abstract

“…Histone deacetylase (HDAC) inhibitors have been studied preclinically for use in a variety of inflammatory disorders and have been studied in the context of parturition (40)(41)(42)(43). It has been observed that histone deacetylation increases at term in the myometrium (43) and in the cervix (44,45). Here, we present findings using HDAC inhibitors for the prevention of PTB in a preclinical murine model.…”

Section: Introductionmentioning

confidence: 95%

Enhanced drug delivery to the reproductive tract using nanomedicine reveals therapeutic options for prevention of preterm birth

et al. 2021

View full text Add to dashboard Cite

Inflammation contributes to nearly 4 million global premature births annually. Here, we used a mouse model of intrauterine inflammation to test clinically used formulations, as well as engineered nanoformulations, for the prevention of preterm birth (PTB). We observed that neither systemic 17a-hydroxyprogesterone caproate (Makena) nor vaginal progesterone gel (Crinone) was sufficient to prevent inflammation-induced PTB, consistent with recent clinical trial failures. However, we found that vaginal delivery of mucoinert nanosuspensions of histone deacetylase (HDAC) inhibitors, in some cases with the addition of progesterone, prevented PTB and resulted in delivery of live pups exhibiting neurotypical development. In human myometrial cells in vitro, the P4/HDAC inhibitor combination both inhibited cell contractility and promoted the anti-inflammatory action of P4 by increasing progesterone receptor B stability. Here, we demonstrate the use of vaginally delivered drugs to prevent intrauterine inflammation–induced PTB resulting in the birth of live offspring in a preclinical animal model.

show abstract

Evolution of Gene Expression in the Uterine Cervix related to Steroid Signaling: Conserved features in the regulation of cervical ripening

Cited by 11 publications

References 57 publications

Decidual cell FKBP51–progesterone receptor binding mediates maternal stress–induced preterm birth

Decidual cell FKBP51–progesterone receptor binding mediates maternal stress–induced preterm birth

Identification and Characterization of Circular RNA as a Novel Regulator and Biomarker in Preterm Birth

Enhanced drug delivery to the reproductive tract using nanomedicine reveals therapeutic options for prevention of preterm birth

Contact Info

Product

Resources

About