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 and endothelial function in vitro. WHAT IS KNOWN ALREADY:FGR is associated with placental insufficiency, where defective trophoblast and endothelial functions contribute to reduced feto-placental growth. STUDY DESIGN, SIZE, DURATION:The expression of FPR2 in placental tissues from human pregnancies complicated with FGR was compared to that in gestation-matched uncomplicated control pregnancies (n = 25 from each group). Fpr2 expression was also determined in placental tissues obtained from a murine model of FGR (n = 4). The functional role of FPR2 in primary trophoblasts and endothelial cells in vitro was assessed in diverse assays in a time-dependent manner. PARTICIPANTS/MATERIALS, SETTING, METHODS:Placentae from third-trimester pregnancies complicated by idiopathic FGR (n = 25) and those from gestation-matched pregnancies with appropriately grown infants as controls (n = 25) were collected at gestation 27-40 weeks. Placental tissues were also collected from a spontaneous CBA/CaH × DBA/2 J murine model of FGR. Placental FPR2/Fpr2 mRNA expression was determined by real-time PCR, while protein expression was examined by immunoblotting and immunohistochemistry. siRNA transfection was used to silence FPR2 expression in primary trophoblasts and in human umbilical vein endothelial cells (HUVEC), and the quantitation of cytokines, chemokines and apoptosis was performed following a cDNA array analyses. Functional effects of trophoblast differentiation were measured using HCGB/β-hCG and syncytin-2 expression as well as markers of apoptosis, tumour protein 53 (TP53), caspase 8, B cell lymphoma 2 (BCL2) and BCL associated X (BAX). Endothelial function was assessed by proliferation, network formation and permeability assays. MAIN RESULTS AND THE ROLE OF CHANCE:Placental FPR2/Fpr2 expression was significantly decreased in FGR placentae (n = 25, P < 0.05) as well as in murine FGR placentae compared to controls (n = 4, P < 0.05). FPR2 siRNA (siFPR2) in term trophoblasts significantly increased differentiation markers, HCGB and syncytin-2; cytokines, interleukin (IL)-6, CXCL8; and apoptotic markers, TP53, caspase 8 and BAX, but significantly reduced the expression of the chemokines CXCL12 and its receptors CXCR4 and CXCR7; CXCL16 and its receptor, CXCR6; and cytokine, IL-10, compared with control siRNA (siCONT). Treatment of HUVECs with siFPR2 significantly reduced proliferation and endothelial tube formation, but significantly increased permeability of HUVECs. LARGE SCALE DATA:N/A. LIMITATIONS, REASONS FOR CAUTION:Reduced expression of placental FPR2/Fpr2 was observed in the third trimester at delivery after development of FGR, suggesting that FPR2 is associated with FGR pregnancies. However, there is a possibility that the decreased placental FPR2 observed in FGR may be a consequence rather than a cause of FGR, although our in vitro functional analyses using primary trophoblasts and endothelial cells suggest that FPR2 may have a direct or indirect regulatory role on trophoblast differentiation and endothelial function in FGR. WIDER IMPLICATIONS OF THE FINDINGS:This is the first study linking placental FPR2 expression with changes in the trophoblast and endothelial functions that may explain the placental insufficiency observed in FGR. STUDY FUNDING/COMPETING INTERESTS:P.M. and P.R.E. received funding from the Australian Institute of Musculoskeletal Science, Western Health, St. Albans, Victoria 3021, Australia. M.L. is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; Grant no. 1047025). Monash Health is supported by the Victorian Government's Operational Infrastructure Support Programme. The authors declare that there is no conflict of interest in publishing this work.
journal_name
Mol Hum Reprodjournal_title
Molecular human reproductionauthors
Lappas M,McCracken S,McKelvey K,Lim R,James J,Roberts CT,Fournier T,Alfaidy N,Powell KL,Borg AJ,Morris JM,Leaw B,Singh H,Ebeling PR,Wallace EM,Parry LJ,Dimitriadis E,Murthi Pdoi
10.1093/molehr/gax067subject
Has Abstractpub_date
2018-02-01 00:00:00pages
94-109issue
2eissn
1360-9947issn
1460-2407pii
4763662journal_volume
24pub_type
杂志文章abstract::The androgen receptor (AR) gene is located on the X chromosome and contains a polymorphic CAG tract. CAG repeat expansions in the AR have been associated with male infertility and the neuromuscular disease, spinal bulbar muscular atrophy (SBMA). Based on Mendelian inheritance patterns, moderate CAG expansions in infer...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/6.9.861
更新日期:2000-09-01 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::Matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), and MMP-TIMP interactions may contribute to the highly programmed process of embryo implantation. The loss of the delicate MMP-TIMP balance may lead to abnormal implantation. The role of TIMP-4 in mouse implantation has not been reported....
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gag019
更新日期:2003-03-01 00:00:00
abstract::Mouse cauda epididymis were in-vivo transfected using the lipid FuGENE 6 as gene vector. Two gene constructions were employed: the p-GeneGRIP which codifies for the Green Fluorescent Protein (GFP) and the pSEAP-control that expresses an alkaline phosphatase as a secretion. Transfection was detected by fluorescence and...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gap026
更新日期:2009-06-01 00:00:00
abstract::This study was undertaken to evaluate the effects of gamma-aminobutyric acid (GABA) and GABAergic agonists and antagonists on sperm kinematic parameters and hyperactivation, evaluated by a computer-assisted semen analysis (CASA) system, and intracellular cAMP content in 22 normozoospermic semen samples. Because of the...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/2.10.733
更新日期:1996-10-01 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:STUDY HYPOTHESIS:In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture. STUDY FINDING:We demonstrate mechanistic differences between preterm birt...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gav074
更新日期:2016-02-01 00:00:00
abstract::Mammalian sperm undergo a series of maturation steps before acquiring fertilization competence. Our previous work demonstrated the importance of binder of sperm (BSP) proteins in bovine sperm capacitation. Recent studies identified a BSP-homologous DNA sequence in the human genome (BSPH1) and mRNA expression in the ep...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gan077
更新日期:2009-02-01 00:00:00
abstract::The preimplantation period of life in mammals encompasses a tremendous amount of restructuring and remodeling of the embryonic genome and reprogramming of gene expression. These vast changes support metabolic activation and cellular processes that drive early cleavage divisions and enable the creation of the earliest ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaz001
更新日期:2019-03-01 00:00:00
abstract::Endometriosis is a gynaecological disease with a certain genetic background, but the locations of possible genomic aberrations are still poorly clarified. Intercellular adhesion molecule-1 (ICAM-1), which is a surface glycoprotein that promotes adhesion in immunological and inflammatory reactions, seems to play a role...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gag002
更新日期:2003-01-01 00:00:00
abstract::The endocrine disrupting chemical o, p'-dichlorodiphenyltrichloroethane (DDT) can affect reproductive organs, tissues and cells in several species. Treatment of human endometrial endothelial cells (HEECs) with 50 microM o,p'-DDT decreased their proliferation compared with the control. Microarray analyses revealed that...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gam091
更新日期:2008-02-01 00:00:00
abstract::Virtually all testicular germ cell tumours originate from a common precursor, the carcinoma in situ (CIS) cell. The precise nature of the molecular mechanisms leading to CIS remains largely unknown. We performed the first systematic analysis of gene expression in testis with CIS compared to normal testis by the differ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gah059
更新日期:2004-06-01 00:00:00
abstract:STUDY QUESTION:Does a heterozygous mutation in AMHR2, identified in whole-exome sequencings (WES) of patients with primary ovarian insufficiency (POI), cause a defect in anti-Müllerian hormone (AMH) signaling? SUMMARY ANSWER:The I209N mutation at the adenosine triphosphate binding domain of AMHR2 exerts dominant negat...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaw040
更新日期:2016-09-01 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::In the interest of classifying cases of male factor infertility, we have paid particular attention to the sugar ligand binding properties of the human sperm surface and the functional capacity of the acrosome for exocytosis--key parameters for assessing sperm fertilizing ability. Zona recognition and binding involve t...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.10.827
更新日期:1997-10-01 00:00:00
abstract::In spite of progress in diagnosis and treatment, prostate cancer has become one of the most frequent lethal cancers in males in many Western industrialized countries. Research on the molecular biology of prostate cancer is expected to reveal those aspects of Western lifestyle contributing to its high incidence with th...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/gag064
更新日期:2003-08-01 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::Preimplantation development shifts from a maternal to embryonic programme rapidly after fertilization. Although the majority of oogenetic products are lost during the maternal to embryonic transition (MET), several do survive this interval to contribute directly to supporting preimplantation development. Embryonic gen...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gan063
更新日期:2008-12-01 00:00:00
abstract::Oocyte quality is one of the most important aspects of in vitro embryo development. Extensive epigenetic programming must occur during oocyte growth and maturation. A specific DNA methylation pattern of the imprinted genes must be established on differentially methylated regions (DMR). The insulin-like growth factor 2...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaq075
更新日期:2011-02-01 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::The etiology of preeclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. Although many candidate genes for preeclampsia have been suggested and studied, the specific causative genes still remain to be identified. Catechol-O-methyltransferase (COMT...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gar014
更新日期:2011-07-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is relevant for normal pregnancy, and abnormalities in VEGF functions are associated with hypertensive disorders of pregnancy. Because there are few studies on how VEGF genetic polymorphisms affect susceptibility to pre-eclampsia (PE), and no studies on how they affect suscept...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gan076
更新日期:2009-02-01 00:00:00
abstract:STUDY HYPOTHESIS:Does a preferential X chromosome inactivation (XCI) pattern exist in female human pluripotent stem cells (hPSCs) and does the pattern change during long-term culture or upon differentiation? STUDY FINDING:We identified two independent phenomena that lead to aberrant XCI patterns in female hPSC: a rapi...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaw004
更新日期:2016-04-01 00:00:00
abstract::In women with premature ovarian failure, fertility may be preserved by ovarian tissue culture in vitro. However, techniques for tissue culture and follicle maturation have remained suboptimal. Our aim was to characterize ovarian tissue degeneration in cultures and to establish a model for cell death research in cultur...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/8.3.228
更新日期:2002-03-01 00:00:00
abstract::Follicular prostaglandin concentrations increase following the gonadotrophin surge in domestic animals and rodents approximately 10 h before follicle rupture, suggesting a unifying role for prostaglandins in the timing of ovulation. However, little is known about prostaglandin production by the primate ovulatory folli...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/7.8.731
更新日期:2001-08-01 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::A major challenge in the comprehension of the endometrial transformations leading to the completion of each menstrual cycle in humans is in the identification of specific molecular pathways underlying these monthly turnovers. Towards this goal we compared, by the differential display technique, the relative expression...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gag084
更新日期:2003-11-01 00:00:00
abstract::The 2019 novel coronavirus (2019-nCoV) appeared in December 2019 and then spread throughout the world rapidly. The virus invades the target cell by binding to angiotensin-converting enzyme (ACE) 2 and modulates the expression of ACE2 in host cells. ACE2, a pivotal component of the renin-angiotensin system, exerts its ...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/gaaa030
更新日期:2020-06-01 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::Although many candidate genes have been studied in pre-eclampsia (PE), the important class of catecholamine receptors that contribute to sympathetic tone and blood pressure regulation has yet to be investigated. We therefore examined the dopamine D4 receptor (DRD4) gene. We performed a prospective family-based study i...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gal004
更新日期:2006-02-01 00:00:00