Abstract:
:Prostaglandin F2α (PGF2α) plays a critical role in the initiation and process of parturition. Since human labor has been described as an inflammatory event, we investigated the role of PGF2α in the inflammatory process using cultured human uterine smooth muscle cells (HUSMCs) isolated from term pregnant women as a model. Using a multiplex assay, HUSMCs treated with PGF2α changed their output of a number of cytokines and chemokines, with a distinct response pattern that differed between HUSMCs isolated from the upper and lower segment region of the uterus. Confirmatory enzyme-linked immunosorbent assays (ELISAs) showed that PGF2α stimulated increased output of interleukin (IL) 1β, IL6, IL8 (CXCL8) and monocyte chemotactic protein-1 (MCP1, also known as chemokine (c-c motif) ligand 2, CCL2) by HUSMCs isolated from both upper and lower uterine segments. In contrast, PGF2α inhibited tumor necrosis factor α (TNFα) release by HUMSCs from the lower uterine segment while the output of TNFα was undetectable in the upper segment. Small interfering (si) RNA mediated knockdown of the PGF2α receptor prevented the changes in cytokine and chemokine output by the HUSMCs. Since the PGF2α receptor (PTGFR) couples via the Gq protein and subsequently activates the phospholipase C (PLC) and protein kinase C (PKC) signaling pathways, we examined the role of these pathways in PGF2α modulation of the cytokines. Inhibition of PLC and PKC reversed the effects of PGF2α. PGF2α activated multiple signaling pathways including extracellular signal-regulated kinases (ERK) 1/2, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), P38, calcineurin/nuclear factor of activated T-cells (NFAT) and NF-κB signaling. Inhibition of ERK reversed PGF2α-induced IL1β, IL6 and CCL2 output, while inhibition of PI3K blocked the effect of PGF2α on IL6, CXCL8 and CCL2 output and inhibition of NF-κB reversed PGF2α-induced IL1β and CCL2 output. NFAT was involved in PGF2α modulation of CCL2 and TNFα output. In conclusion, our results support a role of PGF2α in creating an inflammatory environment during the late stage of human pregnancy.
journal_name
Mol Hum Reprodjournal_title
Molecular human reproductionauthors
Xu C,Liu W,You X,Leimert K,Popowycz K,Fang X,Wood SL,Slater DM,Sun Q,Gu H,Olson DM,Ni Xdoi
10.1093/molehr/gav018subject
Has Abstractpub_date
2015-07-01 00:00:00pages
603-14issue
7eissn
1360-9947issn
1460-2407pii
gav018journal_volume
21pub_type
杂志文章abstract::The effect of interferon-gamma on indoleamine 2,3-dioxygenase, a tryptophan catabolizing enzyme, was studied in cultured human placental chorionic villi. The activity of indoleamine 2,3-dioxygenase was markedly stimulated by interferon-gamma in a time- and concentration-dependent manner. Interferon-alpha and interfero...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/6.4.369
更新日期:2000-04-01 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::We have previously reported that endometrial expression of matrix metalloproteinase (MMP)-26 mRNA comes to a maximum in the early secretory phase. Since tissue inhibitor of metalloproteinase (TIMP)-4 is a potent inhibitor of MMP-26, the objective of this study was to identify the pattern of TIMP-4 mRNA expression in t...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gah092
更新日期:2004-09-01 00:00:00
abstract::During pregnancy, a cervical connective tissue remodelling takes place, clinically recognized as softening, effacement and dilatation. The role of oestrogens and their receptors (ER) in this process is not clear. ERalpha is a ligand-activated transcription factor involved in many physiological processes. The identific...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/7.3.293
更新日期:2001-03-01 00:00:00
abstract::The human endometrium is a dynamic tissue, which undergoes extensive tissue remodelling during the menstrual cycle. Due to their involvement in such processes, several well-characterized matrix metalloproteinases (MMP) have previously been studied in the endometrium. MMP-26 is a newly described matrilysin. We studied ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gag039
更新日期:2003-05-01 00:00:00
abstract::This study was initiated to determine the relationship between the fertilizing potential of spermatozoa and abnormalities in the compact packing of their chromatin which occurs in the final stage of male germ cell differentiation. Chromatin packing involves disulphide bridge covalent cross-linking. The degree of packi...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/5.9.825
更新日期:1999-09-01 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
abstract::Villous tissues from 30 spontaneous abortions and the same number of artificial abortions were obtained and analysed for the frequency of polyploid cells. Single cell suspensions were made from these tissues without culture and the ploidy of > 100 cells was analysed. Trisomies of chromosomes 17 and 4 have rarely been ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.5.445
更新日期:1997-05-01 00:00:00
abstract:STUDY QUESTION:Is oxidative stress associated with the A disintegrin and metalloproteases (ADAM) metallopeptidase domain 17 (ADAM17)/Notch signalling pathway and fibrosis in the development of endometriosis? SUMMARY ANSWER:Oxidative stress is correlated with hyperactivation of the ADAM17/Notch signalling pathway and a...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gax028
更新日期:2017-07-01 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:STUDY QUESTION:What is the association between placental formyl peptide receptor 2 (FPR2) and trophoblast and endothelial functions in pregnancies affected by foetal growth restriction (FGR)? SUMMARY ANSWER:Reduced FPR2 placental expression in idiopathic FGR results in significantly altered trophoblast differentiation...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gax067
更新日期:2018-02-01 00:00:00
abstract::PKDREJ is a testis-specific protein thought to be located on the sperm surface. Functional studies in the mouse revealed that loss of PKDREJ has effects on sperm transport and the ability to undergo an induced acrosome reaction. Thus, PKDREJ has been considered a potential target of post-copulatory sexual selection in...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gau095
更新日期:2015-02-01 00:00:00
abstract::We have previously demonstrated that the reduced form of vitamin C (l-ascorbic acid, AA) is able to induce the production of both steroid and peptide hormones in human choriocarcinoma cells. Here, we attempted to investigate the role and underlying mechanism of the oxidized form of vitamin C, dehydroascorbic acid (DHA...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gau036
更新日期:2014-08-01 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::This study assessed the participation of amphiregulin (AREG) and bone morphogenetic protein 15 (BMP15) during maturation of bovine cumulus-oocyte complexes (COCs) on cumulus cell function and their impact on subsequent embryo development. AREG treatment of COCs enhanced blastocyst formation and quality only when in th...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gau013
更新日期:2014-06-01 00:00:00
abstract::The DAZL (DAZ-like) gene is suggested to be an ancestral gene of the DAZ (deleted in azoospermia) gene on the Y chromosome, which is a strong candidate for the azoospermic factor. Recently, it has been reported that the T54A (Thr54-->Ala) polymorphism in exon 3 of the DAZL gene is associated with spermatogenic failure...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gah202
更新日期:2005-07-01 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::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::Oocyte vitrification has been introduced into clinical settings without extensive pre-clinical safety testing. In this study, we analysed major safety aspects of human oocyte vitrification in a high security closed system: (i) chromosomal meiotic segregation, (ii) embryonic developmental kinetics and (iii) DNA (hydrox...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gav013
更新日期:2015-06-01 00:00:00
abstract::We aimed to confirm the ovarian site of gonadotrophin surge-attenuating factor (GnSAF) production and produce granulosa/luteal cell-conditioned medium (G/LCM) containing GnSAF for purification studies. Blue dye affinity chromatography followed by pseudochromatofocusing of G/LCM yielded bioactive fractions at pH 5.74 a...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/8.9.823
更新日期:2002-09-01 00:00:00
abstract:STUDY QUESTION:Could a more detailed evaluation of marmoset spermatogonial morphology, kinetics and niches using high-resolution light microscopy (HRLM) lead to new findings? SUMMARY ANSWER:Three subtypes of marmoset undifferentiated spermatogonia, which were not evenly distributed in terms of number and position alon...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gay017
更新日期:2018-06-01 00:00:00
abstract::In the implantation, trophoblasts penetrate maternal decidua by secreting proteases. It has been reported that cathepsins are highly expressed in the mouse villi, and play an important role in normal embryonal growth and decidualization. In this study, we evaluated cathepsins and their endogenous inhibitors, cystatins...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gah172
更新日期:2005-05-01 00:00:00
abstract::It is widely assumed that, after ovulation, the human endometrium undergoes specific changes and becomes receptive to the implantation of embryo during the mid-secretory phase. When implantation does not take place, further changes occur which eventually result in the shedding of human endometrium. The present study w...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/6.7.627
更新日期:2000-07-01 00:00:00
abstract::Etoposide is widely used in the treatment of patients with testicular cancer. The mechanism underlying apoptosis induction in cancer cells has been studied in different cell types, but it is not known whether the same factors participate in viable germ cells undergoing programmed cell death. Since testicular cancer pr...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gap024
更新日期:2009-06-01 00:00:00
abstract::Patients with endometriosis are characterized by the ability of the endometrium to implant and by the peritoneal response to the tissue; angiogenic factors may play a significant role in the aetiology of endometriosis supporting the implantation of ectopic endometrial cells. Vascular endothelial growth factor (VEGF) i...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/6.1.50
更新日期:2000-01-01 00:00:00
abstract:STUDY QUESTION:Does dynamin regulate human sperm acrosomal exocytosis? SUMMARY ANSWER:Our studies of dynamin localization and function have implicated this family of mechanoenzymes in the regulation of progesterone-induced acrosomal exocytosis in human spermatozoa. WHAT IS KNOWN ALREADY:Completion of an acrosome reac...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gax044
更新日期:2017-10-01 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::Analysis of small numbers of chromosomes using interphase fluorescent in-situ hybridization (FISH) probes has revealed that 50% of human preimplantation embryos contain abnormal cells. Detection of high levels of mosaicism with so few probes has led some researchers to extrapolate that a full analysis of all 23 pairs ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/6.11.1055
更新日期:2000-11-01 00:00:00
abstract::Success rate in human pregnancies is believed to be very low and sex-specific mechanisms may operate in prenatal loss. Assuming a sex-differential in prenatal loss exists, we examined genetic markers in biologically plausible targets in the HLA complex, other immune system-related and iron-regulatory genes in 388 heal...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaq047
更新日期:2010-10-01 00:00:00
abstract::In mammals, egg activation is initiated by multiple cytosolic Ca(2+) transients (Ca(2+) oscillations) that are triggered following delivery of a putative sperm factor from the fertilizing sperm. The identity of this 'sperm factor' thus holds much significance, not only as a vital component in creating a new life, but ...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/gav009
更新日期:2015-05-01 00:00:00