Prostaglandin F2-alpha receptor regulation in human uterine myocytes

Liang, Zhiqing; Sooranna, Suren R.; Engineer, N.; Tattersall, Mark; Khanjani, Shirin; Bennett, Phillip R.; Myatt, Leslie; Johnson, Mark R.

doi:10.1093/molehr/gan008

Cited by 24 publications

(12 citation statements)

References 31 publications

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“…For example, we and others have demonstrated that IL-1β, TNFα and IL-6 can increase prostaglandin production by amnion, decidua and myometrium [11, 21, 22, 70, 73, 138–140, 155, 175, 198, 199, 202, 294, 325]. PTGS2/COX2 is a rapidly inducible enzyme with reported increased expression in association with labor in myometrium [5, 6, 44, 54, 67, 115, 136, 233, 278, 284, 289, 306] and the uterine cervix [26, 67, 132, 186, 230, 297, 313, 330, 331].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

Mittal¹,

Romero²,

Tarca³

et al. 2010

Journal of Perinatal Medicine

141

113

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Aims: To characterize the transcriptome of human myometrium during spontaneous labor at term. Methods: Myometrium was obtained from women with (ns19) and without labor (ns20). Illumina ᭨ HumanHT-12 microarrays were utilized. Moderated t-tests and false discovery rate adjustment of P-values were applied. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for a select set of differentially expressed genes in a separate set of samples. Enzyme-linked immunosorbent assay and Western blot were utilized to confirm differential protein production in a third sample set. Results: 1) Four hundred and seventy-one genes were differentially expressed; 2) gene ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using signaling pathway impact analysis indicated six significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-STAT signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) systemic lupus erythematosus; and f) chemokine signaling pathway; 4) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2, heparin binding epidermal growth factor (EGF)-like growth factor, chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5, interleukin (IL)-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta, suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 and aldehyde dehydrogenase in labor; 5) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group. Conclusions: Myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene expression identified with microarray was confirmed with qRT-PCR using an independent set of samples. This study represents an unbiased description of the biological processes involved in spontaneous labor at term based on transcriptomics.

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Section: Discussionmentioning

confidence: 99%

Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

Mittal¹,

Romero²,

Tarca³

et al. 2010

Journal of Perinatal Medicine

141

113

View full text Add to dashboard Cite

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“…Secondly, NF‐κB leads to inflammatory cell migration into the myometrium, with a consequent marked increase in local cytokine concentrations. These cytokines would then stimulate synthesis of prostaglandins [47, 48], induce calcium entry into myometrial smooth‐muscle cells [49], increasing their contractility, and stimulate phosphodiesterase activity, leading to a decrease in cAMP (adenosine monophosphate) concentrations [50].…”

Section: Discussionmentioning

confidence: 99%

NF-κB regulates a cassette of immune/inflammatory genes in human pregnant myometrium at term

Khanjani

Kandola

Lindström

et al. 2011

Journal of Cellular and Molecular Medicine

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The onset of human labour resembles inflammation with increased synthesis of prostaglandins and cytokines. There is evidence from rodent models for an important role for nuclear factor-κB (NF-κB) activity in myometrium which both up-regulates contraction-associated proteins and antagonizes the relaxatory effects of progesterone. Here we show that in the human, although there are no differences in expression of NF-κB p65, or IκB-α between upper- or lower-segment myometrium or before or after labour, there is nuclear localization of serine-256-phospho-p65 and serine-536-phospho-p65 in both upper- and lower-segment myometrium both before and after the onset of labour at term. This shows that NF-κB is active in both upper and lower segment prior to the onset of labour at term. To identify the range of genes regulated by NF-κB we overexpressed p65 in myocytes in culture. This led to NF-κB activation identical to that seen following interleukin (IL)-1β stimulation, including phosphorylation and nuclear translocation of p65 and p50. cDNA microarray analysis showed that NF-κB increased expression of 38 genes principally related to immunity and inflammation. IL-1β stimulation also resulted in an increase in the expression of the same genes. Transfection with siRNA against p65 abolished the response to IL-1β proving a central role for NF-κB. We conclude that NF-κB is active in myocytes in both the upper and lower segment of the uterus prior to the onset of labour at term and principally regulates a group of immune/inflammation associated genes, demonstrating that myocytes can act as immune as well as contractile cells.

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“…Oxytocin is synthesized in the neurohypophysis and enhances secretion of prostaglandin F2α (PGF2α) in endometrial stroma and glandular cells and expression of the PGF2α receptor. 76,77 Systemic oxytocin administration in the follicular phase increases the amplitude of uterine contractions and reverses the pressure gradient from fundal cervical to cervical fundal as measured with IUP. 23 Vasopressin, another nonapeptide synthesized in the neurohypophysis, mediates its effects through subtype receptors including the V1A subtype receptor 78 found in the uterus.…”

Section: Potential Therapeuticsmentioning

confidence: 99%

Impairment of Uterine Contractility Is Associated with Unexplained Infertility

Hunt

Abdallah

et al. 2020

Semin Reprod Med

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The uterine junctional zone represents the juncture between endometrium and myometrium. The junctional zone is hormonally dependent and displays continuous peristaltic activity throughout the menstrual cycle in the nonpregnant state which is concerned with sperm transport and embryo implantation. Peristalsis may be observed using various invasive and noninvasive modalities, of which ultrasound is the most readily applied in the clinical setting. Women with pelvic pathology display alterations in uterine peristalsis which may contribute to infertility. Characterization of peristalsis in infertility subgroups, the development of a subjective peristalsis tool, and the application of potential therapeutics to an assisted reproductive treatment setting are the subject of ongoing investigation. Meta-analysis indicates a potential role for oxytocin antagonist in the improvement of fertility treatments.

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Prostaglandin F2-alpha receptor regulation in human uterine myocytes

Cited by 24 publications

References 31 publications

Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

NF-κB regulates a cassette of immune/inflammatory genes in human pregnant myometrium at term

Impairment of Uterine Contractility Is Associated with Unexplained Infertility

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