Alteration of secretory leukocyte protease inhibitor in human myometrium during labor

Li, Aimin; Lee, Richard H.; Felix, Janine F.; Minoo, Parviz; Goodwin, T. Murphy

doi:10.1016/j.ajog.2008.10.045

Cited by 5 publications

(2 citation statements)

References 41 publications

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“…In addition, it has been reported that the intervillous blood flow is present in an early stage ( i.e. < seventh week) [ 26 ] and increases gradually from fourth week during the first trimester of pregnancy [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy

et al. 2014

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BackgroundHuman placenta releases specific nanovesicles (i.e. exosomes) into the maternal circulation during pregnancy, however, the presence of placenta-derived exosomes in maternal blood during early pregnancy remains to be established. The aim of this study was to characterise gestational age related changes in the concentration of placenta-derived exosomes during the first trimester of pregnancy (i.e. from 6 to 12 weeks) in plasma from women with normal pregnancies.MethodsA time-series experimental design was used to establish pregnancy-associated changes in maternal plasma exosome concentrations during the first trimester. A series of plasma were collected from normal healthy women (10 patients) at 6, 7, 8, 9, 10, 11 and 12 weeks of gestation (n = 70). We measured the stability of these vesicles by quantifying and observing their protein and miRNA contents after the freeze/thawing processes. Exosomes were isolated by differential and buoyant density centrifugation using a sucrose continuous gradient and characterised by their size distribution and morphology using the nanoparticles tracking analysis (NTA; Nanosight™) and electron microscopy (EM), respectively. The total number of exosomes and placenta-derived exosomes were determined by quantifying the immunoreactive exosomal marker, CD63 and a placenta-specific marker (Placental Alkaline Phosphatase PLAP).ResultsThese nanoparticles are extraordinarily stable. There is no significant decline in their yield with the freeze/thawing processes or change in their EM morphology. NTA identified the presence of 50–150 nm spherical vesicles in maternal plasma as early as 6 weeks of pregnancy. The number of exosomes in maternal circulation increased significantly (ANOVA, p = 0.002) with the progression of pregnancy (from 6 to 12 weeks). The concentration of placenta-derived exosomes in maternal plasma (i.e. PLAP+) increased progressively with gestational age, from 6 weeks 70.6 ± 5.7 pg/ml to 12 weeks 117.5 ± 13.4 pg/ml. Regression analysis showed that weeks is a factor that explains for >70% of the observed variation in plasma exosomal PLAP concentration while the total exosome number only explains 20%.ConclusionsDuring normal healthy pregnancy, the number of exosomes present in the maternal plasma increased significantly with gestational age across the first trimester of pregnancy. This study is a baseline that provides an ideal starting point for developing early detection method for women who subsequently develop pregnancy complications, clinically detected during the second trimester. Early detection of women at risk of pregnancy complications would provide an opportunity to develop and evaluate appropriate intervention strategies to limit acute adverse sequel.

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Section: Discussionmentioning

confidence: 99%

Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy

et al. 2014

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“…Inflammation has been implicated in key biological processes required for reproduction, including ovulation, implantation [63, 97, 203] and parturition[14, 15, 17, 31, 130, 137, 160, 172, 189, 206, 240–242, 244, 249, 251, 255–258, 261, 277, 326]. Implantation of the blastocyst generates a pro-inflammatory response within the decidua (TH1-like polarization) [63, 97, 203].…”

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

142

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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Effect of 17-α hydroxyprogesterone caproate on the production of tumor necrosis factor-α and the expression of cyclooxygenase-2 in lipopolysaccharide-treated gravid human myometrial explants

Patel

Goodwin

et al. 2010

J Perinatol

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Objective: To determine whether 17-a hydroxyprogesterone (17-OHPC) alters tumor necrosis factor-a (TNF-a) production and the expression of cyclooxygenase type 2 (COX-2) in myometrium exposed to lipopolysaccharide (LPS).Study Design: Lower segment myometrial biopsies were obtained from non-laboring patients at term. Tissues were cultured in serum-free media with 17-OHPC (1 mM) and LPS (1 mg/ml), either alone or in combination. At 24 h, the production of tumor necrosis factor-a (TNF-a) and the expression of COX-2 was determined using enzyme linked immunosorbent assay and real-time (RT-PCR). Statistical analysis was performed using non-parametric testing. A P-value of <0.05 was considered significant.Result: 17-OHPC had no effect on TNF-a production and COX-2 expression when compared with untreated myometrial explants (P ¼ 0.61 and P ¼ 0.95). LPS induced production of TNF-a (P ¼ 0.03) and expression of COX-2 (P ¼ 0.02). Treatment with 17-OHPC did not block LPS-induced TNF-a production (P ¼ 0.37) or COX-2 expression (P ¼ 0.12). Conclusion:In this pilot study, 17-OHPC did not affect the production of TNF-a or COX-2 expression in human myometrium.

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Alteration of secretory leukocyte protease inhibitor in human myometrium during labor

Cited by 5 publications

References 41 publications

Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy

Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy

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

Effect of 17-α hydroxyprogesterone caproate on the production of tumor necrosis factor-α and the expression of cyclooxygenase-2 in lipopolysaccharide-treated gravid human myometrial explants

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