John Aplin
The University of Manchester, Medicine and human sciences, Faculty Member
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Research Interests: Technology, Stem Cells, Biology, Cell Biology, Medicine, and 15 moreBiological Sciences, Pregnancy, Humans, Female, Animals, STEM, Mesenchymal Stem Cell, Integrins, Rats, Stromal Cells, Base Sequence, Mesenchymal Stromal Cells, Microchimerism, Vascular endothelial growth factor receptor, and Medical and Health Sciences
The purpose of this study was to compare the morphologic features of placentas in severe intrauterine fetal growth restriction with abnormal umbilical artery blood flow velocity waveforms and normal gestation. Immunohistochemical methods... more
The purpose of this study was to compare the morphologic features of placentas in severe intrauterine fetal growth restriction with abnormal umbilical artery blood flow velocity waveforms and normal gestation. Immunohistochemical methods were used to evaluate cell proliferation, vascular density, and alpha-smooth muscle actin expression by stromal cells in a group of 9 age-matched intrauterine growth-restricted and control placentas at 25 to 41 weeks of gestation. Fewer MIB1-positive nuclei were observed in both trophoblast and stromal cell populations in intrauterine growth restriction, which indicates fewer cells in cycle. Furthermore, a greatly reduced vascular density was observed, along with higher levels of alpha-smooth muscle actin expression in stromal cells. Intrauterine growth-restricted placentas show reduced cell proliferation in both trophoblast and stromal cell compartments. Peripheral villous vascularization is highly reduced.
Research Interests: Andrology, Biology, Prediction, Morphology, Medicine, and 15 moreCell Division, Pregnancy, Humans, Placenta, Resistance, Female, Newborn Infant, Fetal Growth Restriction, Flow Velocity, Fetus, Cell Proliferation, Blood Flow Velocity, Intrauterine Growth Restriction, Paediatrics and reproductive medicine, and Fetal Growth Retardation
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Database mining revealed 102 extracellular matrix (ECM) genes amongst about 10000 mRNA species expressed in human placenta, and these were classified into collagens (23), non-collagenous glycoproteins (59) and proteoglycans (23). A panel... more
Database mining revealed 102 extracellular matrix (ECM) genes amongst about 10000 mRNA species expressed in human placenta, and these were classified into collagens (23), non-collagenous glycoproteins (59) and proteoglycans (23). A panel of antibodies to selected collagens and glycoproteins was used to examine ECM distribution in the placental villous stroma. Collagens I and IV, fibronectin and fibrillin I were abundant in first trimester and term tissue. Some areas lacked collagen I, while collagen IV was clearly evident in interstitial locations. At term, laminin was present in the stroma as well as in trophoblastic and vascular basement membranes. Thrombospondin I, tenascin C and elastin showed more restricted distributions. Fibrosis has been reported in association with ischaemia, so ECM production by cultured term and first trimester placental fibroblasts was evaluated at three different oxygen concentrations. Fibronectin and collagen IV were more strongly expressed than collagen I, fibrillin I or thrombospondin I, while the production of laminin and elastin was very low. Reducing the oxygen tension led to a selective increase in fibronectin and collagen IV production. Thus both quantitative and qualitative alterations in ECM composition may be expected to accompany prolonged hypoxia.
Research Interests: Chemistry, Biology, Hypoxia, Medicine, Gene expression, and 15 moreExtracellular Matrix, Humans, Basement Membrane, Placenta, Female, Clinical Sciences, Elastin, Fibronectin, Oxygen, Adult, Enzyme Linked Immunosorbent Assay, Extracellular Matrix Proteins, Laminin, fibroblasts, and Paediatrics and reproductive medicine
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During the preimplantation phase, the endometrium undergoes a variety of histological (Dallenbach-Hellweg, 1981) and compositional (Bell, 1986; Aplin, 1989) alterations. These are believed to create an appropriate milieu for the... more
During the preimplantation phase, the endometrium undergoes a variety of histological (Dallenbach-Hellweg, 1981) and compositional (Bell, 1986; Aplin, 1989) alterations. These are believed to create an appropriate milieu for the implanting blastocyst. The changes include the production of secretory material for the implanting blastocyst; the alteration of cell surface composition at the luminal epithelium; and changes in the stromal environment. We (Seif et al., 1989) and others (Bell, 1986) have reported previously studies of hormonally regulated secretory components of human endometrium and decidua. Here we describe an approach to the characterization of endometrial cell surfaces during the menstrual cycle which may be useful both in furthering understanding of reproductive function and in diagnosis of reproductive failure. We have focused on endometrial epithelium since this forms the site of initial interaction of maternal and fetal cells.
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The presence of cell adhesion molecules on human oocytes, early embryos, and pre-hatched blastocysts was examined by indirect immunofluorescence and compared to the distribution found on first trimester villous placenta with the same... more
The presence of cell adhesion molecules on human oocytes, early embryos, and pre-hatched blastocysts was examined by indirect immunofluorescence and compared to the distribution found on first trimester villous placenta with the same antibodies. Six integrin subunits (alpha 3, alpha V, beta 1, beta 3, beta 4, beta 5) were observed consistently throughout preimplantation development. Evidence was also obtained for the presence of integrin subunits alpha 2, alpha 4, alpha L, beta 2, and beta 7 on a small number of oocytes. A more restricted developmental analysis of E-cadherin, ICAM-1, NCAM, and VCAM-1 demonstrated that these cell adhesion molecules are also present on oocytes and early embryos. L-selectin was detected on oocytes but was not found on 8-cell embryos. The oocyte and early blastomeres have complex surfaces in which the integrin and CAM families are represented.
Research Interests: Fluorescence Microscopy, Biology, Cell Adhesion, Medicine, Embryo, and 15 moreHumans, Female, Blastocyst, Clinical Sciences, Human reproduction, Human Embryo, Cadherin, Oocytes, Embryos, Oocyte, Integrin, Cell Adhesion Molecules, Cadherins, Medical and Health Sciences, and Paediatrics and reproductive medicine
Research Interests: Biology, Medicine, Pregnancy, Humans, Mice, and 15 moreFemale, Ovulation, Animals, Gynecology and Obstetrics, Monoclonal Antibodies, Menstrual Cycle, Fluorescent Antibody Technique, Epithelium, Monoclonal Antibody, Cell Surface Markers, Epitopes, Endometrium, Antigen, Follicular phase, and Paediatrics and reproductive medicine
Research Interests: Biology, Cell Biology, Apoptosis, Medicine, Extracellular Matrix, and 15 moreHuman, Pregnancy, Humans, Female, Human reproduction, Trophoblast, Cell Proliferation, Pre Eclampsia, Matrix Metalloproteinase, Fas Ligand, Arteries, Smooth muscle cell, coculture techniques, Choriocarcinoma, and Medical and Health Sciences
Research Interests: Biology, Medicine, Embryo, Biological Sciences, Humans, and 15 moreMice, Female, Animals, Monoclonal Antibodies, Biochemical, Menstrual Cycle, CHEMICAL SCIENCES, Glycosaminoglycans, Molecular Mass, Monoclonal Antibody, Epitopes, Endometrium, Oligosaccharides, epitope, and Medical and Health Sciences
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Research Interests: Molecular Biology, Biology, Immunohistochemistry, Medicine, Cell line, and 15 moreHumans, Mice, Female, Animals, Monoclonal Antibodies, Integrins, Antibody, Epithelium, Monoclonal Antibody, Amino Acid Sequence, Cell Surface Markers, Cervical Intraepithelial Neoplasia, Integrin, Molecular Sequence Data, and Uterine Cervical Neoplasms
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The distribution of keratan sulphate (KS) in normal endometrium has been studied by immunohistochemistry using monoclonal antibody 5D4. KS is present in association with glandular epithelium throughout the normal cycle. Production is... more
The distribution of keratan sulphate (KS) in normal endometrium has been studied by immunohistochemistry using monoclonal antibody 5D4. KS is present in association with glandular epithelium throughout the normal cycle. Production is hormonally regulated, as indicated by the significant increase observed in the secretory phase of the cycle. Intracellular immunoreactivity increases to a maximum 3 days after the luteinizing hormone (LH) peak. This is followed by an increase in secreted KS from 4 days after the LH peak, and essentially all endometrial glands showed immunoreactive deposits by 5 days after the LH peak. Beginning on day 7 after the LH peak, a fraction of glands was observed to have lost the epitope. Nevertheless, KS remained in a significant proportion of the gland lumens 9 days after the LH peak. The data suggest that analysis of secretory KS in women gives an index of hormonally regulated epithelial differentiation in the peri-implantation phase.
Research Interests: Endocrinology, Chemistry, Immunohistochemistry, Adolescent, Medicine, and 15 moreHumans, Internal Medicine, Female, Monoclonal Antibodies, Implantation, Menstrual Cycle, Human reproduction, Adult, Time Factors, Retrospective Studies, Luteinizing Hormone, Endometrium, Secretion, Medical and Health Sciences, and Luteal phase
Human decidua contains resident decidual cells alongside a population of bone marrow-derived cells, among which macrophages and large granular lymphocytes are most abundant. We hypothesized that soluble effectors produced by bone... more
Human decidua contains resident decidual cells alongside a population of bone marrow-derived cells, among which macrophages and large granular lymphocytes are most abundant. We hypothesized that soluble effectors produced by bone marrow-derived cells may modulate the function of the decidual cells. To investigate this, a cell purification protocol was devised that involved digestion of first-trimester decidua with collagenase and hyaluronidase to produce a mixed stromal cell suspension from which the bone marrow-derived cells were removed using immunomagnetic beads coated with anti-CD45. The resulting stromal cells were maintained in culture in the presence of progesterone and were found to produce PRL. The effect of a panel of cytokines on PRL production was examined. Tumor necrosis factors-alpha and -beta had a dose-dependent inhibitory effect, and tumor necrosis factor receptors were identified on the cells. Interleukin 1 alpha and 1 beta, platelet-derived growth factor, and transforming growth factor-beta 1 were also found to inhibit PRL production, and platelet-derived growth factor and transforming growth factor-beta 1 stimulated cell proliferation. These findings suggest an interaction between the immune and endocrine systems in regulating the maternal environment of early pregnancy.
Research Interests: Endocrinology, Cultural Studies, Biology, Cytokines, Macrophages, and 15 moreMedicine, Pregnancy, Progesterone, Humans, Internal Medicine, Female, Clinical, Bone marrow, Clinical Sciences, Cytokine, Lymphocytes, Bone Marrow Cells, Interleukin, Paediatrics and reproductive medicine, and Immunomagnetic separation
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Decidual spiral arteriole (SpA) remodeling is essential to ensure optimal uteroplacental blood flow during human pregnancy, yet very little is known about the regulatory mechanisms. Uterine decidual NK (dNK) cells and macrophages... more
Decidual spiral arteriole (SpA) remodeling is essential to ensure optimal uteroplacental blood flow during human pregnancy, yet very little is known about the regulatory mechanisms. Uterine decidual NK (dNK) cells and macrophages infiltrate the SpAs and are proposed to initiate remodeling before colonization by extravillous trophoblasts (EVTs); however, the trigger for their infiltration is unknown. Using human first trimester placenta, decidua, primary dNK cells, and macrophages, we tested the hypothesis that EVTs activate SpA endothelial cells to secrete chemokines that have the potential to recruit maternal immune cells into SpAs. Gene array, real-time PCR, and ELISA analyses showed that treatment of endothelial cells with EVT conditioned medium significantly increased production of two chemokines, CCL14 and CXCL6. CCL14 induced chemotaxis of both dNK cells and decidual macrophages, whereas CXCL6 also induced dNK cell migration. Analysis of the decidua basalis from early pregnanc...
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A fibroblast cell strain that expressed cytokeratins 8 and 18 was isolated from explanted first trimester placenta. Its properties were consistent with an origin in the villous fibroblast-myofibroblast lineage, including expression of... more
A fibroblast cell strain that expressed cytokeratins 8 and 18 was isolated from explanted first trimester placenta. Its properties were consistent with an origin in the villous fibroblast-myofibroblast lineage, including expression of vimentin, smooth muscle alpha-actin and fibroblast surface protein. The cells grew rapidly in vitro, and exhibited tightly aligned bipolar morphology at confluence, absence of multi-nucleated cells, lack of secreted chorionic gonadotrophin, and absence of HLA G, placental alkaline phosphatase and pregnancy-specific beta-1 glycoprotein (SP1). On these criteria it was concluded they were not trophoblasts. On the basis of their morphology, cytokeratin expression and absence of CD34 and endoglin it was concluded they were not endothelial cells. They lacked desmin and smooth muscle myosin and so were not vascular smooth muscle cells. Further mesenchymal cell isolates were studied to determine the generality of these findings. Phenotypic heterogeneity was a consistent characteristic, but cytokeratin-positive cells were always present both in first trimester and term strains. Desmin was absent from almost all the cells isolated using the protocols employed, despite its occurrence in a significant subpopulation of cells in the villous stroma. Cytokeratins 8 and 18 can be observed in the stromal compartment of both first trimester and term placental villi. Cytokeratin has hitherto been regarded as a highly reliable marker for cells of the trophoblast lineage in vitro. These observations suggest that care should be taken in characterization of placental cell isolates; trophoblasts should be identified by the presence of cytokeratin 7 in preference to cytokeratin 8/18. The functional significance of cytokeratin expression in placental mesenchymal cells remains to be established.
Research Interests: Biology, Medicine, Cytoskeleton, Pregnancy, Humans, and 15 moreSmooth muscle, Placenta, Female, Alkaline phosphatase, Phenotype, Clinical Sciences, Endothelial cell, Trophoblast, Biological markers, Cytokeratin, Vimentin, Keratins, Vascular Smooth Muscle, fibroblasts, and Paediatrics and reproductive medicine
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Anchoring villi are peripheral trophoblastic specializations that attach the placenta to the uterine wall. In addition, they supply the migratory trophoblast population that colonizes the maternal interstitium and arteries during the... more
Anchoring villi are peripheral trophoblastic specializations that attach the placenta to the uterine wall. In addition, they supply the migratory trophoblast population that colonizes the maternal interstitium and arteries during the first 18 weeks of pregnancy. Establishment of anchoring villi and subsequent invasion of maternal uterine stroma and blood vessels play a critical role in pregnancy success; incomplete vascular invasion is associated with common pathological conditions of pregnancy, including spontaneous abortion, pre-eclampsia and growth retardation. Anchoring villi are already present as early as 18 days after ovulation, but new villi develop rapidly as the placenta grows. First trimester mesenchymal floating villi, when confronted with a permissive extracellular matrix (ECM) in explant culture, undergo de novo development of anchoring sites. The cellular and molecular characteristics of these specializations closely resemble those that are seen in vivo. It is postulated that development of new sites is important in the stabilization of placental attachment during growth and development in the first trimester. This may be compromised by function-blocking antibodies which inhibit cell--ECM interactions. This is supported by experiments in vitro as well as by the presence of auto-antibodies to adhesion molecules in women suffering from recurrent spontaneous miscarriage.
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Research Interests: Biology, Fertility, Infertility, Medicine, Abortion, and 15 moreEmbryo, Pregnancy, Humans, Biomedical Research, Female, Animals, Implantation, Human reproduction, In vitro models, Female Infertility, Embryos, Endometrium, Assisted Reproductive Technique, embryo implantation, and Paediatrics and reproductive medicine
Research Interests: Endocrinology, Biology, DNA replication, Medicine, Extracellular Matrix, and 15 morePregnancy, Humans, Placenta, Female, Clinical, Polymerase Chain Reaction, Fibrosis, Clinical Sciences, Fibronectin, Transforming Growth Factor Beta, Base Sequence, Enzyme Linked Immunosorbent Assay, Transforming Growth Factor, fibroblasts, and Paediatrics and reproductive medicine
Challenge lies ahead in unravelling the role played by trophoblast and its repertoire of expressed genes in normal human placental development, growth and pathology. Specific technical advances will clearly be required for... more
Challenge lies ahead in unravelling the role played by trophoblast and its repertoire of expressed genes in normal human placental development, growth and pathology. Specific technical advances will clearly be required for characterisation of function. In particular, improvements in our repertoire of in vitro models are needed before many of the key questions can be answered. Recent advances in the study of human trophoblast differentiation are discussed.
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A systematic review revealed three small randomised controlled trials of yoga for low back pain, all of which showed effects on back pain that favoured the yoga group. To build on these studies a larger trial, with longer term follow-up,... more
A systematic review revealed three small randomised controlled trials of yoga for low back pain, all of which showed effects on back pain that favoured the yoga group. To build on these studies a larger trial, with longer term follow-up, and a number.
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ABSTRACT
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Research Interests: Biology, Medicine, Western blotting, Pregnancy, Humans, and 15 morePlacenta, Female, American, Elastin, Biological markers, Myocyte, Uterus, Gestation, Aorta, Gene expression profiling, Matrix Metalloproteinase, Vascular Smooth Muscle, reverse transcriptase polymerase chain reaction, Medical and Health Sciences, and Uterine Artery
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Secretory differentiation of endometrium after multiple follicular stimulation using gonadotrophin releasing hormone and human menopausal gonadotrophin has been studied both histologically and immunohistochemically in 30 women undergoing... more
Secretory differentiation of endometrium after multiple follicular stimulation using gonadotrophin releasing hormone and human menopausal gonadotrophin has been studied both histologically and immunohistochemically in 30 women undergoing in-vitro fertilization treatment. None had embryo transfer. Patients were randomly allocated to receive luteal phase support with a single dose of human chorionic gonadotrophin. The latter failed to produce any significant enhancement of endometrial structure or secretions. Appropriate glandular morphology was present in a greater proportion of those who were successfully stimulated than those who responded poorly. However, defective secretion of the cycle-dependent component studied, using monoclonal antibody D9B1, was demonstrated in two-thirds of cases regardless of the ovarian response. Early vascular maturation in the stroma was a common finding, and was thus considered as a feature of structural modulation of these endometria.
Research Interests: Andrology, Biology, Immunohistochemistry, Medicine, Biopsy, and 15 moreHuman, Progesterone, Humans, In Vitro Fertilisation, Female, Embryo Transfer, Human reproduction, Fertilization in Vitro, Endometrium, Estradiol, Follicular phase, embryo implantation, Medical and Health Sciences, Chorionic gonadotropin, and Luteal phase
Research Interests: Biology, Immunohistochemistry, Medicine, Humans, Fertility and Sterility, and 12 moreFemale, Obstetrics and Gynaecology, Monoclonal Antibodies, Clinical Sciences, Public health systems and services research, Monoclonal Antibody, Female Infertility, Endometrium, Corpus Luteum, epitope, Paediatrics and reproductive medicine, and Luteal phase
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This paper reports the pattern of production and secretion of a secretory phase epitope in the endometrium of 44 normal fertile women. Peroxidase immunochemistry was used to detect the monoclonal antibody D9B1, which binds to a... more
This paper reports the pattern of production and secretion of a secretory phase epitope in the endometrium of 44 normal fertile women. Peroxidase immunochemistry was used to detect the monoclonal antibody D9B1, which binds to a peptide-associated sialylated oligosaccharide, in endometrial biopsies all chronologically dated from the luteinizing hormone (LH) peak. During the proliferative phase, the epitope was shown to be absent from tissue sections. It first made its appearance within gland cells 2 days after the LH peak. By LH+3 a rapid accumulation of the D9B1 epitope was noted in the base of the cell, below the nucleus. On subsequent days, increasing amounts of the antigen were detected in the apical cytoplasm, apparently in a more concentrated form than in the basal cell zone. On day LH+6, around the time of implantation, secretory vesicles in the cell apex were discharged into the gland lumen where the glycoconjugate finally accumulated. This immunohistochemical approach introduces a new parameter for evaluation of endometrial function and could be used to improve the accuracy of histological assessment of the endometrial cycle.
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Research Interests: Polysaccharides, Infertility, Medicine, Biopsy, Humans, and 15 moreFertility and Sterility, Female, Clinical Sciences, Adult, Public health systems and services research, Analysis of Variance, Luteinizing Hormone, Epitopes, Endometrial Biopsy, Endometrium, Oligosaccharides, Mifepristone, epitope, Paediatrics and reproductive medicine, and Luteal phase
Research Interests: Biology, Immunohistochemistry, Medicine, Prospective studies, Humans, and 12 moreFertility and Sterility, Female, Menstrual Cycle, Clinical Sciences, Adult, Public health systems and services research, Endometrium, Progestins, Dydrogesterone, Paediatrics and reproductive medicine, primary ovarian insufficiency, and Luteal phase
Research Interests: Chemistry, Biology, Cell Biology, Medicine, Immunofluorescence, and 14 moreHuman, Pregnancy, Female, Intermediate Filaments, Integrins, Epithelium, Conference paper, Hemidesmosome, Amnion, Cytokeratin, Integrin, Biochemistry and cell biology, Immunoblotting, and Medical biochemistry and metabolomics
During pregnancy, the resident stromal cells of the endometrium differentiate to become decidual cells and produce a pericellular basement membrane. We used immunofluorescence and Western blotting with a panel of monoclonal Ab specific... more
During pregnancy, the resident stromal cells of the endometrium differentiate to become decidual cells and produce a pericellular basement membrane. We used immunofluorescence and Western blotting with a panel of monoclonal Ab specific for various laminin subunits to examine the composition of decidual laminin. The stromal cell basement membrane contained subunits alpha 2 (M), beta 1 (B1), beta 2 (S), and gamma 1 (B2). Low levels of alpha 1 could also be detected. The glandular and vascular basement membranes of decidual tissue contained subunits alpha 1 (A), beta 1, and gamma 1. An extract was produced from decidual extracellular matrix. Western blots of nonreducing gels showed the presence of high molecular weight complexes containing alpha 2, beta 1, beta 2, and gamma 1. These data indicated that laminins 2 and 4 are coexpressed by decidual cells. Laminin 1 was present in the extract as a minor component. In contrast, cultured stromal cells expressed laminin 1 as the major secret...
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After ovulation, progesterone stimulates a temporally regulated secretory transformation in human endometrial epithelium. Using a combination of immunohistochemistry, and Western and Northern blotting, we demonstrate that 1) the... more
After ovulation, progesterone stimulates a temporally regulated secretory transformation in human endometrial epithelium. Using a combination of immunohistochemistry, and Western and Northern blotting, we demonstrate that 1) the polymorphic epithelial mucin MUC1 is secreted by human endometrial epithelium; 2) low levels of both mRNA and core protein are present in the preovulatory phase of the menstrual cycle; 3) mRNA levels increase several-fold after ovulation, consistent with transcriptional regulation by progesterone; 4) there is an increase in translation product in postovulatory endometrium; and 5) the tandem repeat domain of the MUC-1 polypeptide is glycosylated in endometrium.