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::Human chromosome deletions in Yq11 seem to occur frequently as de novo mutation events in men with idiopathic azoospermia or severe oligozoospermia. However, the molecular extensions of these deletions are variable. They can be large and therefore visible under the microscope or small, not visible under the microscope...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/4.8.739
更新日期:1998-08-01 00:00:00
abstract::The Prader-Willi (PWS) and Angelman (AS) syndromes are two clinically distinct syndromes which result from lack of expression of imprinted genes within chromosome 15q11-q13. These two syndromes result from 15q11-q13 deletions, chromosome 15 uniparental disomy (UPD), imprinting centre mutations and, for AS, probable mu...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/3.4.321
更新日期:1997-04-01 00:00:00
abstract::The causes for recurrent spontaneous abortion (RSA) remain unknown in a large proportion of the cases. Human leukocyte antigen (HLA)-G and HLA-E are expressed on invasive trophoblast cells, and are supposed to confer to materno-fetal tolerance. A total of 14 different nucleotide sequences have been described for HLA-G...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/7.4.373
更新日期:2001-04-01 00:00:00
abstract::Recombinant human ZP3 (rhuZP3) generated by Chinese hamster ovary cells transfected with a plasmid containing human ZP3 cDNA was used to study the acrosome reaction (AR) and intracellular calcium fluxes in capacitated human spermatozoa. Conditioned medium containing rhuZP3 significantly induced the AR (P < or = 0.005)...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/2.8.583
更新日期:1996-08-01 00:00:00
abstract::Within the context of an oocyte in vitro maturation (IVM) program for reproductive treatment, oocyte cumulus complexes (COCs) derived from follicles <6 mm in patients with PCOS were matured in vitro. Key transcripts related to meiotic maturation (FSHR, LHCGR, EGFR, PGR) and oocyte competence (AREG, ADAMTS, HAS2, PTGS2...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gas038
更新日期:2013-01-01 00:00:00
abstract::Sperm experience intense and varied selection that dramatically impacts the evolution of sperm quality. Selection acts to ensure that sperm are fertilization-competent and able to overcome the many challenges experienced on their way towards eggs. However, simply being able to fertilize an egg is not enough to ensure ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gau067
更新日期:2014-12-01 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::A molecule isolated from the peritoneal fluids of women undergoing laparoscopy for in-vitro fertilization techniques has been chemically characterized and identified as 1-palmitic-3-phosphorylcholine (lysophosphatidylcholine, LPC). This lipid is able, at physiological concentrations, to completely inhibit sperm motili...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.3.241
更新日期:1997-03-01 00:00:00
abstract::In addition to prostaglandins, inflammatory cytokines induce uterine contraction via oxytocin (OT). Placental leucine aminopeptidase (P-LAP), an oxytocinase that is identical to cystine aminopeptidase, destroys OT activity. Patients with spontaneous preterm delivery have higher concentrations of inflammatory cytokines...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gag015
更新日期:2003-02-01 00:00:00
abstract::Human sperm contain similar amounts of protamine-1 (P1) and protamine-2 (P2). Although an aberrant protamine ratio have been observed in subfertile men, functional evidence is provided by protamine knockout mice exhibiting male infertility. As sperm DNA integrity is known to be linked with DNA fragmentation and apopto...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gar011
更新日期:2011-07-01 00:00:00
abstract::It is widely held that the first two blastomeres of mammalian embryos are equally totipotent and that this totipotency belongs to the group of regulative properties. However, this interpretation neglects an important aspect: evidence only came from successful monozygotic twins which can speak only for those pairs of h...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaz051
更新日期:2019-11-30 00:00:00
abstract::The transcription factor OCT-4 is regarded as a critical factor in controlling mammalian early embryonic development because of its role in toti-/pluripotency. In human preimplantation embryos, OCT-4 studies are limited to RNA analysis of abnormally developing embryos. This study thoroughly investigated the expression...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gah155
更新日期:2005-03-01 00:00:00
abstract::We have developed a competitive reverse transcription-polymerase chain reaction (RT-PCR) sensitive enough to detect and quantify as little as 2-fold differences in gene expression in individual oocytes and embryos throughout human preimplantation development. This RT-PCR assay can be tailored for the examination of an...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/7.2.147
更新日期:2001-02-01 00:00:00
abstract::Successful intracytoplasmic sperm injection (ICSI) is dependent upon the competence of the oocyte to respond to the injection of a spermatozoon in the presence of calcium. This study determined if oocytes that failed to become fertilized (absence of any pronuclei) failed to undergo cytoplasmic activation, as ascertain...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/2.12.959
更新日期:1996-12-01 00:00:00
abstract::Observational human data and several lines of animal experimental data indicate that maternal obesity impairs offspring health. Here, we comprehensively tested the model that maternal obesity causes defects in the next three generations of oocytes and embryos. We exposed female F0 mice to a high-fat/high-sugar (HF/HS)...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaz049
更新日期:2019-11-30 00:00:00
abstract:STUDY QUESTION:Is it possible to identify original compounds that are able to enhance sperm motility from the venom of the scorpion Scorpio maurus palmatus? SUMMARY ANSWER:We identified a potent disulfide-rich peptide (DRP) of 73 amino acids that significantly improved the motility of fresh and frozen-thawed sperm in ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaw075
更新日期:2017-02-10 00:00:00
abstract::The human endometrium is a cyclically regenerating organ under the influence of ovarian steroid hormones. Disturbances in this highly coordinated regulation of endometrial proliferation and differentiation may result in infertility and diseases such as endometriosis and endometrial cancer. Environmental toxins belongi...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaq081
更新日期:2011-02-01 00:00:00
abstract::The major regulators of endometrial function are oestrogen and progesterone, which act through binding their nuclear receptors and by activating transcription of their target genes. Interactions between steroid receptors and transcription proteins, e.g. c-JUN/AP-1, can modulate steroid action at the transcriptional le...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/4.12.1110
更新日期:1998-12-01 00:00:00
abstract::In order to improve assisted fertilization in humans it is important to elucidate the mechanisms of control of growth and development in the early pre-embryo. Increasing evidence shows that growth factors are of importance for such control mechanisms. As platelet-derived growth factor (PDGF) has been shown to enhance ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/2.7.507
更新日期:1996-07-01 00:00:00
abstract::Prader-Willi syndrome (PWS) is a genomic disorder mostly caused by deletions of 15q11-q13 region (70%). It has been suggested that the particular genomic architecture of 15q11-q13 region, characterized to be flanked by low copy repeats, could predispose it to Non-Allelic Homologous Recombination (NAHR). However, no st...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaq005
更新日期:2010-05-01 00:00:00
abstract::The molecular mechanism of stress-associated reproductive dysfunction is complex and largely unknown. This study was designed to systematically analyze molecular effects of systemic in vivo blockade of α1-adrenergic receptors (α1-ADRs) on stress-induced disturbance of cAMP/cGMP signaling in testosterone-producing Leyd...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gat052
更新日期:2014-01-01 00:00:00
abstract::Follicular development and ovulation are major processes in the reproductive system. Understanding their complexity is important to female fertility treatments and the control of reproductive processes. Wnt signaling pathway components were shown to be involved in reproduction in animal models. The secreted frizzled-r...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gar010
更新日期:2011-07-01 00:00:00
abstract::In Europe up to one in four couples experience difficulty conceiving and in half of these cases the problem has been attributed to sub or infertility in the male partner. The development of assisted reproductive technologies (ART) such as in vitro fertilization and intra-cytoplasmic spermatozoa injection has allowed s...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/gam089
更新日期:2008-01-01 00:00:00
abstract::MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression post-transcriptionally. We explored whether connexin 43 (Cx43) was differently expressed in luteinized granulosa cells from women with polycystic ovary syndrome (PCOS) compared with luteinized granulosa cells from women with a normal...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaaa044
更新日期:2020-08-01 00:00:00
abstract::The expression of insulin-like growth factor-I (IGF-I) was measured at the mRNA and protein level in myometrium and fibroids from women with and without preoperative treatment with a gonadotrophin-releasing hormone (GnRH) agonist for 3 months, from post-menopausal women, from pregnant women and in myometrium from wome...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/6.10.915
更新日期:2000-10-01 00:00:00
abstract::The requisite endpoint of mammalian oocyte maturation, whether in vivo or in vitro, is a metaphase II oocyte which is able to be fertilized and which can eventually support normal embryonic development. Oocytes which have been matured in vivo basically fulfill these criteria. On the other hand, a completely different ...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/4.1.41
更新日期:1998-01-01 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::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::Inhibin production has been demonstrated in malignant epithelial ovarian tumours, but secretion of inhibins by benign cystadenoma has not yet been reported. The present study evaluated the concentrations of inhibin A and inhibin B and the relationship with oestradiol and nitric oxide metabolites in fluid collected fro...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/6.12.1079
更新日期:2000-12-01 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