A5027031359- Reproductive System and Pregnancy
- Pregnancy and preeclampsia studies
- Endometriosis Research and Treatment
- Immune Cell Function and Interaction
- Preterm Birth and Chorioamnionitis
- Pregnancy and Medication Impact
- Ectopic Pregnancy Diagnosis and Management
- Reproductive Physiology in Livestock
- Neonatal Respiratory Health Research
- Birth, Development, and Health
- T-cell and B-cell Immunology
- Chemokine receptors and signaling
- Cell Adhesion Molecules Research
- Uterine Myomas and Treatments
- Renal and related cancers
- IL-33, ST2, and ILC Pathways
- Pregnancy-related medical research
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Health Systems, Economic Evaluations, Quality of Life
- COVID-19 Impact on Reproduction
- Spine and Intervertebral Disc Pathology
- Immunotherapy and Immune Responses
- Estrogen and related hormone effects
- Prenatal Screening and Diagnostics
University of Cambridge
2015-2024
NIHR Newcastle Biomedical Research Centre
2023
Queen's Hospital
2022
Westmead Hospital
2021
The University of Queensland
2021
Robert Jones and Agnes Hunt Orthopaedic Hospital
2002-2009
Lawn Tennis Association
2008
Keele University
2002-2006
Newcastle University
2005
MRC Human Nutrition Research
2001
Many common disorders of pregnancy are attributed to insufficient invasion the uterine lining by trophoblast, fetal cells that major cell type placenta. Interactions between trophoblast and maternal NK (uNK) cells--specifically interactions HLA-C molecules expressed killer Ig-like receptors (KIRs) on uNK cells--influence placentation in human pregnancy. Consistent with this, pregnancies at increased risk preeclampsia mothers homozygous for KIR haplotype A (KIR AA). In this study, we have...
Abstract The endometrium, the mucosal lining of uterus, undergoes dynamic changes throughout menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps human uterus three-dimensional endometrial organoid cultures. dissect signaling pathways that determine cell fate epithelial lineages lumenal glandular microenvironments. Our benchmark organoids reveals states regulating differentiation secretory ciliated both vivo vitro. In vitro...
BMP is thought to induce hESC differentiation toward multiple lineages including mesoderm and trophoblast. The BMP-induced trophoblast phenotype a long-standing paradox in stem cell biology. Here we readdressed function hESCs mouse epiblast-derived cells. We found that BMP4 cooperates with FGF2 (via ERK) inhibit endoderm differentiation. These conditions induced cells high levels of BRACHYURY (BRA) coexpressed CDX2. BRA was necessary for preceded CDX2 expression; both genes were essential...
Human trophoblast cells express an unusual repertoire of human leucocyte antigen (HLA) molecules which has been difficult to define. Close homology between and extreme polymorphism at the classical HLA class-I (HLA-I) loci made it generate locus-specific monoclonal antibodies (mAbs). The problem defining antibody's reactivity against thousands existing HLA-I allotypes often impossible determine bound by a mAb in biological samples from normal outbred population. Here we have used...
Highlights•Criteria to identify human trophoblast cells in vitro are controversial•HLA class I profile and methylation of ELF5 confirmed as good markers•Levels C19MC miRNAs a novel marker•Using these criteria, BMP4-, A83-01-, PD173074-treated hESC not trophoblastSummaryControversy surrounds reports describing the derivation from placentas embryonic stem (ESC), partly due difficulty identifying markers that define belonging lineage. We have selected criteria characteristic primary...
Reduced trophoblast invasion and vascular conversion in decidua are thought to be the primary defect of common pregnancy disorders including preeclampsia fetal growth restriction. Genetic studies suggest these conditions linked combinations polymorphic killer cell Ig-like receptor (KIR) genes expressed by maternal decidual NK cells (dNK) HLA-C trophoblast. Inhibitory KIR2DL1 activating KIR2DS1 both bind HLA-C2, but confer increased risk or protection from disorders, respectively. The...
Significance Fetal extravillous trophoblasts (EVT) invade uterine tissue and interact with maternal immune cells during pregnancy. EVT express human leukocyte antigen-C (HLA-C) -G (HLA-G). Although polymorphic HLA-C can elicit a response, HLA-G has been associated induction of tolerance. We have succeeded in isolating all cell types as well from placental tissue. These methods were used to elucidate the unique charateristics their interaction cells. demonstrate that are specialized whose...
Abstract The relationship between the human placenta—the extraembryonic organ made by fetus, and decidua—the mucosal layer of uterus, is essential to nurture protect fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate decidua, transforming maternal arteries into high-conductance vessels 1 . Defects in invasion arterial transformation established early pregnancy underlie common disorders such as pre-eclampsia 2 Here we have generated a...
In humans, balanced invasion of trophoblast cells into the uterine mucosa, decidua, is critical for successful pregnancy. Evidence suggests that this process regulated by natural killer (uNK) cells, but how they influence reproductive outcomes unclear. Here, we used our organoids and primary tissue samples to determine uNK affect placentation. By locating potential interaction axes between using single-cell transcriptomics in vitro modeling these interactions organoids, identify a...
Angiogenesis is essential for endometrial growth and repair, disruption of this process may lead to common disorders women, including menorrhagia endometriosis. In pregnancy, failure the spiral arterioles undergo remodeling leads preeclampsia. Here we report that in addition vascular endothelial factor A (VEGF-A), human endometrium expresses messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta (PlGF), angiopoietins, angiopoietin 1 (Ang1) Ang2, receptors VEGFR-3 (Flt-4), Tie 1, 2....
The remodelling of the maternal uterine spiral arteries during pregnancy, known as physiological change, is critical for normal growth and development fetus. Controversy has surrounded part played by fetal trophoblast in transformation these arteries. To address this debate, a histological immunochemical comparison blood vessels from implantation sites human pregnancies early gestation with tissue where was absent performed. Results showed that true features medial necrosis deposition...
Dendritic cells (DCs) in the pregnant human uterine mucosa have been poorly characterized, although they are likely to regulate immune responses both placental trophoblast and infections. In this study an HLA-DR+, CD11c+ lin− (CD3−, CD19−, CD56−, CD14−) population has identified by three-color flow cytometry. The cell isolates were prepared either collagenase digestion or mechanically from first-trimester decidual tissue. DCs comprised ∼1.7% of CD45+ had phenotype immature myeloid DCs. No...
In healthy individuals, the non-classical MHC molecule HLA-G is only expressed on fetal trophoblast cells that invade decidua during placentation. We show a significant proportion of at surface normal human present as disulphide-linked homodimer conventional beta(2)m-associated HLA-I complex. ligand for leukocyte immunoglobulin-like receptors (LILR), which bind much more efficiently to dimeric than molecules. find LILRB1-Fc fusion protein preferentially binds form cells. detect LILRB1...
The mammalian fetus represents a semiallograft within the maternal uterus yet is not rejected. This situation particularly pronounced in species with hemochorial type of placentation, such as humans and rodents, where tissues blood are direct contact fetal trophoblast thus potentially paternal antigens. main polymorphic antigens responsible for graft rejection MHC In cells invading into decidua have unique pattern class I expression characterized by both classical (HLA-C) nonclassical (HLA-G...
Abstract Immunogenetic studies suggest that interactions between maternal killer Ig-like receptor (KIR) expressed by uterine NK (uNK) cells, and fetal HLA-C molecules on trophoblast, influence the success of human placentation. However, exact functional response fresh uNK cells to trophoblast is unknown. In this study, we show quantitative RT-PCR FACS both activating inhibitory KIR specific for are at higher levels an increased proportion in decidua compared with blood. contrast, expression...
Abstract Innate lymphoid cells (ILCs), including NK cells, contribute to barrier immunity and tissue homeostasis. In addition the role of uterine in placentation fetal growth, other ILCs (uILCs) are likely play roles physiology pathology. this article, we report on composition uILCs endometrium during luteal phase decidua early pregnancy. Whereas nonkiller uILC1s uILC2s barely detectable mouse not detected humans, a sizeable population uILC3s is found human decidua, which mostly NCR+...
We have examined the transcriptional changes associated with differentiation from villous to extravillous trophoblast using a whole genome microarray. Villous (VT) is in contact maternal blood and mediates nutrient exchange whereas (EVT) invades decidua remodels uterine arteries. Using highly purified first trimester we identified over 3000 transcripts that are differentially expressed. Many of these represent novel functions pathways show co-ordinated up-regulation VT or EVT. In addition...