Abstract:
STUDY QUESTION:Does A20 regulate mediators involved in the terminal processes of human labour in primary myometrial and amnion cells? SUMMARY ANSWER:A20 is a nuclear factor-kappa B (NF-κB) responsive gene that acts as a negative regulator of NF-κB-induced expression of pro-labour mediators. WHAT IS KNOWN ALREADY:Inflammation is commonly implicated in spontaneous preterm birth and the processes involved in rupture of foetal membranes and uterine contractions. In myometrium and foetal membranes, the pro-inflammatory transcription factor NF-κB regulates the transcription of pro-labour mediators in response to inflammatory stimuli. In non-gestational tissues, A20 is widely recognised as an anti-inflammatory protein that inhibits inflammation-induced NF-κB signalling. STUDY DESIGN, SIZE, DURATION:Primary human amnion and myometrial cells were used to determine the effect of pro-inflammatory mediators on A20 expression and the effect of A20 siRNA on the expression and secretion of pro-labour mediators. The expression of A20 was assessed in myometrium and foetal membranes from non-labouring and labouring women at preterm and or term (n = 8 or nine samples per group). PARTICIPANTS/MATERIALS, SETTING, METHODS:The effects of pro-inflammatory mediators and of A20 siRNA in cell cultures were determined by quantitative RT-PCR (qRT-PCR), western blots, immunoassays, gelatin zymography and luciferase assays. A20 expression in tissue samples was assessed by qRT-PCR. Statistical significance was ascribed to a P value < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE:In primary cells isolated from myometrium and or amnion, the pro-inflammatory cytokines IL1B and TNF, the bacterial products flagellin and fsl-1, and the viral double stranded RNA analogue poly(I:C) significantly increased A20 mRNA expression via NF-κB. A20 siRNA studies in primary myometrial and amnion cells demonstrated an augmentation of inflammation-induced expression and or secretion of pro-inflammatory cytokines (IL1A, IL6), chemokines (CXCL1, CXCL8, CCL2), adhesion molecules (ICAM1, VCAM1), contraction-associated proteins (PTGS2, PTGFR, PGF2α) and the extracellular matrix degrading enzyme MMP9, as well as NF-κB activation. Inhibition of NF-κB activity significant attenuated inflammation-induced expression of pro-labour mediators in A20 siRNA transfected cells. Finally, A20 mRNA expression was decreased in myometrium and foetal membranes with labour, and in foetal membranes with chorioamnionitis. LARGE SCALE DATA:Not applicable. LIMITATIONS, REASONS FOR CAUTION:The conclusions of this study are solely reliant on the data from in vitro experiments using cells isolated from myometrium and amnion. WIDER IMPLICATIONS OF THE FINDINGS:The results of this study raise the possibility that targeting A20 may be a therapeutic approach to reduce inflammation associated with spontaneous preterm birth. STUDY FUNDING AND COMPETING INTEREST(S):Associate Professor Martha Lappas is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; grant no. 1047025). Funding for this study was provided by the NHMRC (grant no. 1058786), Norman Beischer Medical Research Foundation and the Mercy Research Foundation. There are no competing interests.
journal_name
Mol Hum Reprodjournal_title
Molecular human reproductionauthors
Lappas Mdoi
10.1093/molehr/gax041subject
Has Abstractpub_date
2017-09-01 00:00:00pages
628-645issue
9eissn
1360-9947issn
1460-2407pii
4037427journal_volume
23pub_type
杂志文章abstract::A complete hydatidiform mole (CHM) is an abnormal pregnancy with hyperproliferative vesicular trophoblast and no fetal development. Most CHM are sporadic and androgenetic, but recurrent HM have biparental inheritance (BiHM) with disrupted DNA methylation at differentially methylated regions (DMRs) of imprinted loci. S...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gam079
更新日期:2008-01-01 00:00:00
abstract::Several studies have demonstrated an association between polycystic ovary syndrome (PCOS) and the dinucleotide repeat microsatellite marker D19S884, which is located in intron 55 of the fibrillin-3 (FBN3) gene. Fibrillins, including FBN1 and 2, interact with latent transforming growth factor (TGF)-beta-binding protein...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gap072
更新日期:2009-12-01 00:00:00
abstract::Antibodies to alpha and beta subunits of guanine nucleotide regulatory proteins (G proteins) were used to identify which G proteins are present in mature human spermatozoa and to determine their subcellular localization. Immunoblots of membranes from spermatozoa demonstrate the presence of Galphai2, Galphai3, Galphaq/...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/5.1.38
更新日期:1999-01-01 00:00:00
abstract::Intense macrophage infiltration is observed during luteolysis in various animals including women; however, we still do not know how macrophage infiltration into the human corpus luteum (CL) during luteolysis is regulated. In this study, we examined the expression, localization and regulation of an important chemokine ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gav028
更新日期:2015-08-01 00:00:00
abstract::Oxidative damage by reactive oxygen species (ROS) is a major cause of sperm dysfunction. Excessive ROS generation reduces fertilization and enhances DNA damage of spermatozoa. Interaction between spermatozoa and oviductal epithelial cells improves the fertilizing ability of and reduces chromatin damage in spermatozoa....
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gav015
更新日期:2015-06-01 00:00:00
abstract:STUDY QUESTION:Can enzymatically dispersed testicular cells from adult men reassemble into seminiferous cord-like structures in vitro? SUMMARY ANSWER:Adult human testicular somatic cells reassembled into testicular cord-like structures via dynamic interactions of Sertoli and peritubular cells. WHAT IS KNOWN ALREADY:I...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gax063
更新日期:2018-02-01 00:00:00
abstract::Immunocytochemistry was used to localize endothelial (eNOS) and inducible (iNOS) nitric oxide synthase in human uterine tissues collected at various stages of the menstrual cycle, after exposure to exogenous progestagens, and in early pregnancy. Endothelial NOS-like immunoreactivity was detected in all specimens in en...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.1.69
更新日期:1997-01-01 00:00:00
abstract::The etiology and pathogenesis of endometriosis are complex with both genetic and environmental factors contributing to disease risk. Genome-wide association studies (GWAS) have identified multiple signals in the estrogen receptor 1 (ESR1) region associated with endometriosis and other reproductive traits and diseases....
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaaa082
更新日期:2021-01-22 00:00:00
abstract::In the uterus, epithelial cell proliferation changes during the estrous cycle and pregnancy. Uncontrolled epithelial cell proliferation results in implantation failure and/or cancer development. Transforming growth factor-β (TGF-β) signaling is a fundamental regulator of diverse biological processes and is indispensab...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gau033
更新日期:2014-08-01 00:00:00
abstract::Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the 'developmental programming' and Developmental Origins of Health and Diseases (DOHaD) have become well...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/gaw036
更新日期:2016-08-01 00:00:00
abstract::Testicular germ cell cancer is aetiologically linked to genital malformations and male infertility and is most probably caused by a disruption of embryonic programming and gonadal development during fetal life. In some cases, germ cell neoplasia is associated with a relative reduction of Y chromosomal material (e.g. 4...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gag069
更新日期:2003-09-01 00:00:00
abstract::Nuclear oligomerization domains (NODs) are cytosolic pattern recognition receptors (PRRs), present in epithelial cells, monocytes and dendritic cells. This study details their expression, regulation and role in human endometrium. Real-time PCR showed that NOD1 mRNA is constitutively expressed in endometrium. NOD2 is u...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gap020
更新日期:2009-05-01 00:00:00
abstract:STUDY QUESTION:Do human adult Leydig cells (ALCs) within hyperplastic micronodules display characteristics of foetal LCs (FLCs)? SUMMARY ANSWER:The gene expression profiles of FLCs and all ALC subgroups were clearly different, but there were no significant differences in expressed genes between the normally clustered ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gax012
更新日期:2017-05-01 00:00:00
abstract::Controlling the sex of offspring by the separation of X and Y chromosome-bearing spermatozoa using flow cytometry has been reported as a clinical technique aiding prevention of X-linked diseases. Although this technique has resulted in several hundred normal births in animals and at least one human birth, there is sti...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.9.821
更新日期:1997-09-01 00:00:00
abstract::The human egg may only be fertilized by one spermatozoon to prevent polyploidy. In most mammals, the primary block to polyspermy occurs at the zona pellucida (ZP). Little is known of the human ZP and the changes occurring following fertilization to prevent polyploidy. Using antibodies directed against synthetic peptid...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/5.6.534
更新日期:1999-06-01 00:00:00
abstract::Fetal membranes overlying the cervix in patients prior to and during labour, and within the rupture tear after spontaneous delivery at term, exhibit altered morphology. In this study we report that in comparison to mid-zone fetal membranes biopsies, these regions are characterized by increased expression of the matric...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/7.5.463
更新日期:2001-05-01 00:00:00
abstract::In early gestation, the human placental renin-angiotensin system (RAS) is upregulated and plays a role in placental development. Among other functions, signalling through the angiotensin II type 1 receptor (AT1R) initiates proliferation. Many microRNAs (miRNAs) targeting placental RAS mRNAs are downregulated at this t...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaz010
更新日期:2019-04-01 00:00:00
abstract::To mimic post-ovulatory ageing, we have extended the in vitro maturation (IVM) phase to 48 h and examined effects on (i) developmental potential, (ii) expression of a panel of developmentally important genes and (iii) gene-specific epigenetic marks. Results were compared with the 24 h IVM protocol (control) usually em...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gav040
更新日期:2015-10-01 00:00:00
abstract:STUDY QUESTION:What is the prevalence, reproducibility and biological significance of transcriptomic differences between sister blastomeres of the mouse 2-cell embryo? SUMMARY ANSWER:Sister 2-cell stage blastomeres are distinguishable from each other by mRNA analysis, attesting to the fact that differentiation starts ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gay021
更新日期:2018-07-01 00:00:00
abstract::Commercial hMG drugs are marketed for the treatment of infertility and consist of highly purified hormones acting on receptors expressed in target gonadal cells. Menopur® and Meriofert® are combined preparation of FSH and hCG and are compared in vitro herein. To this purpose, the molecular composition of the two drugs...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaaa070
更新日期:2020-12-10 00:00:00
abstract::In mature mammalian oocytes, cortical f-actin distribution is polarized, as evidenced by a prominent cap subtended by the metaphase II (MII) spindle. Formation of a polarized actin cap is a consequence of a complex actomyosin-driven contractile process that directs polar body extrusion. Human mature oocytes also displ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gat085
更新日期:2014-03-01 00:00:00
abstract:STUDY QUESTION:Which different pathways and functions are altered in rhesus monkey oocytes that fail to mature after an ovulatory stimulus? SUMMARY ANSWER:Failed to mature (FTM) oocytes complete a large portion of the transition in transcriptome composition associated with normal maturation, but also manifest numerous...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gay032
更新日期:2018-10-01 00:00:00
abstract::Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca(2+) influx and induce contraction. Cationic leak channels, which permit a steady flow of cations into a cell, are known to cause membrane depolariza...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gav038
更新日期:2015-10-01 00:00:00
abstract::The clinical application of quantitative fluorescent polymerase chain reaction (QF-PCR) for rapid prenatal detection of chromosome aneuploidies has been limited in most studies to the detection of autosomal trisomies. Recently it has been shown that a newly identified highly polymorphic marker, termed X22, which maps ...
journal_title:Molecular human reproduction
pub_type: 临床试验,杂志文章
doi:10.1093/molehr/7.10.1001
更新日期:2001-10-01 00:00:00
abstract::Stromal cell-derived factor-1 (SDF-1 or CXCL12) is the physiologic ligand for the chemokine receptor CXCR4. CXCR4-mediated signalling regulates cell migration and apoptosis in certain haematopoietic and neuronal cells. Using gene profiling, we determined that CXCR4 is the only chemokine receptor for which mRNA express...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gah118
更新日期:2004-12-01 00:00:00
abstract::Acrosome status in human spermatozoa from 20 normozoospermic men was evaluated by flow cytometry following the induction of the acrosome reaction with the ionophore A23187. Dual fluorescence staining of methanol fixed spermatozoa incubated with and without (control) the ionophore A23187 was performed with probes which...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/4.3.243
更新日期:1998-03-01 00:00:00
abstract::We report here the molecular cloning and characterization of human haspin cDNA and its genomic DNA construct. The haspin protein is a unique protein kinase, first isolated from mouse testis. Specifically expressed in mouse testicular germ cells, haspin is suggested to play a role in cell cycle arrest in haploid sperma...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/7.3.211
更新日期:2001-03-01 00:00:00
abstract::Natural killer (NK) cells are the predominant leukocyte in first trimester decidua and play a role in vascular remodelling through interferon gamma (IFNgamma) secretion. Membrane expression of the killer immunoglobulin-like receptor (KIR) KIR2DL4 on peripheral blood NK (pNK) cells is controlled by the 9A/10A transmemb...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gap039
更新日期:2009-08-01 00:00:00
abstract::Ever since work on pluripotency induction was originally published, reporting the reprogramming of somatic cells to induced pluripotent stem cells (iPS cells) by the ectopic expression of the four transcription factors Oct4, Sox2, Klf4 and c-Myc, high expectations regarding their potential use for regenerative medicin...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/gaq059
更新日期:2010-11-01 00:00:00
abstract::In recent years, the impact of sperm DNA damage on fertility has become an important issue. The different technologies developed to check sperm DNA fragmentation lead to the same conclusion: DNA damage negatively impacts upon reproductive processes. Oocyte DNA repair capacity is one of the cues to understanding embryo...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gam038
更新日期:2007-08-01 00:00:00