PubMed Health⌕ Search

Biomedical subjects

Siobhan Quenby

Publications and source records attributed to Siobhan Quenby.

12 recordsLinked to original sources
PubMed2006

Uterine natural killer cells, implantation failure and recurrent miscarriage.

Uterine natural killer (uNK) cells are the most abundant leukocytes in preimplantation endometrium and early pregnancy decidua. Maternal uNK cells are adjacent to, and have the ability to interact directly with, fetal trophoblasts. uNK cells can secrete an array of cytokines that are important in angiogenesis and thus placental development and the establishment of pregnancy. Increased numbers of uNK cells have been associated with reproductive failure. The number of preimplantation uNK cells has been reduced with prednisolone. However, despite these exciting advances in understanding of the uNK cells, considerably more work needs to be done to establish a specific role for uNK cells and to use uNK cells as a test of malfunctioning endometrium and the basis for future treatment for reproductive failure.

Abortion, Habitual↗
PubMed2005

Antiphospholipid antibodies prevent extravillous trophoblast differentiation.

OBJECTIVE: We investigated the hypothesis that antiphospholipid antibodies (aPL) have a detrimental effect on human extravillous trophoblast (EVT) differentiation into giant multinucleated cells "in vitro." DESIGN: The EVT were isolated from the placental chorion using enzymatic digestion and Percoll gradient centrifugation. After 24, 36, and 48 hours in culture, giant multinuclear cells (GMC) were identified by immunohistochemistry using antibodies to cytokeratin 7 and counted. SETTING: An academic research laboratory. PATIENT(S): Placentas were donated by women having an elective cesarean section for a normal pregnancy at term. MAIN OUTCOME MEASURE(S): This model was then used to investigate the effect of two different monoclonal aPL to beta2-glycoprotein 1 (IIC5 and ID2), and control mouse IgG antibody on EVT differentiation. RESULT(S): Freshly isolated EVT were nonproliferative but moved together losing their intervening cell walls and differentiated into GMC. Maximal numbers of GMC were detected after 48 hours of culture. The aPL, IIC5, and ID2 significantly inhibited GMC formation, whereas the mouse IgG control had no effect. CONCLUSION(S): Antiphospholipid antibodies can inhibit EVT differentiation and GMC formation "in vitro" suggesting that a failure of trophoblast differentiation and subsequent uteroplacental development may be an underlying pathology in antiphospholipid syndrome-associated pregnancy loss.

Antibodies, Antiphospholipid↗
PubMed2005

Prednisolone reduces preconceptual endometrial natural killer cells in women with recurrent miscarriage.

OBJECTIVE: To test the hypothesis that high numbers of uterine natural killer (uNK) cells in the endometrium of women with recurrent miscarriage (RM) could be reduced with prednisolone. DESIGN: A before and after study. SETTING: A tertiary referral teaching hospital. PATIENT(S): Eighty-five women with idiopathic RM recruited from all over the UK and 18 women attending for sterilization (controls). INTERVENTION(S): An endometrial sample was taken on day 21 +/- 2 of the menstrual cycle. Immunohistochemistry was used to identify uNK (CD56+, CD16-, CD3-). Twenty-nine women with RM and >5% uNK agreed to take 20 mg oral prednisolone daily from day 1 to 21 of their menstrual cycle, when a second biopsy was obtained and analyzed. MAIN OUTCOME MEASURE(S): The percentage of stromal cells that were uNK. The normal range was defined using control samples as <5%. RESULT(S): Women with RM had significantly more uNK than the controls (P=.008). Prednisolone treatment significantly reduced the number of CD56 cells in the endometrium, from a median of 14% (before) to 9% (after) (P=.0004). CONCLUSION(S): We have demonstrated that high numbers of uNK in preimplantation endometrium of women with recurrent miscarriage can be reduced with administration of prednisolone.

Abortion, Habitual↗
PubMed2004

Trophoblast invasion.

Trophoblast invasion can be seen as a tightly regulated battle between the competing interests of the survival of the fetus and those of the mother. Successful pregnancy is dependent on the trophoblast invading the mother, attaching the pregnancy to the uterus and securing an adequate supply of oxygen and nutrient to the fetus. For successful invasion to occur, extravillous trophoblast has to perform a range of functions; transformation of the maternal spiral arteries, tolerate hypoxia, proliferate and die by apoptosis (programmed cell death), differentiate, adhere to and digest the extracellular matrix, move and interact with the maternal immune system. Each of these functions has multiple overlapping control systems so that trophoblast invasion is a finely controlled balance of competing mechanisms.

Apoptosis↗
PubMed2004

Dysfunctional labor and myometrial lactic acidosis.

OBJECTIVE: Inefficient uterine contractions are the most common cause of poor progress in labor. The global increase in cesarean delivery rate is a cause of considerable concern, and the greatest reason for increase is the result of failure to progress in labor. Following in vitro studies that showed acidification could depress uterine contraction, we hypothesized that it could contribute to dysfunctional labors. METHODS: A blood sample was taken from the lower segment of the uterus from women having a cesarean delivery, either electively or as a result of dysfunctional labor, and from those having a normal labor. This blood sample was analyzed for pH, O(2) saturation, and lactate levels. Contraction was recorded in myometrial strips, taken from women having elective cesarean delivery, at the pH of normally and dysfunctionally contracting uteri. RESULTS: The pH of myometrial capillary blood from women having a dysfunctional labor was significantly lower (7.35) than that from women having elective cesarean delivery (7.49) or cesarean delivery with normal contractions, with (7.47) or without (7.48) oxytocin (P <.001). The women in dysfunctional labor had higher capillary lactate and lower capillary O(2) saturation. Furthermore, in vitro, reducing the pH value from 7.5 to 7.3 changes regular uterine contractions to irregular ones of reduced amplitude. CONCLUSIONS: Myometrial lactic acidosis and a small decrease in O(2) saturation may be contributing factors to dysfunctional labor. Our data may also account for the ineffectiveness in management of dysfunctional labor with oxytocin. Oxytocin with a background of lactate acidosis may not be successful. LEVEL OF EVIDENCE: II-2

Acidosis, Lactic↗
PubMed2004

Effects of low-molecular-weight and unfractionated heparin on trophoblast function.

OBJECTIVE: Unfractionated and low-molecular-weight heparin and low-dose aspirin are used for the prevention of pregnancy loss in pregnant women with thrombophilia. We investigated the effect of these drugs on in vitro models of human extravillous trophoblast motility and differentiation. METHODS: Chorion from term placentas was digested and extravillous trophoblast isolated. Extravillous trophoblast formed giant multinuclear cells that were counted after 24, 36, and 48 hours of culture. This model was then used to investigate the effect of unfractionated, low-molecular-weight heparin and aspirin on in vitro extravillous trophoblast differentiation at both therapeutic and supratherapeutic doses. In addition, the effect of unfractionated and low-molecular-weight heparin on hepatocyte growth factor-stimulated SGHPL-4 cell (extravillous trophoblast cell line) motility was determined by time-lapse microscopy. RESULTS: At therapeutic doses unfractionated heparin promoted extravillous trophoblast differentiation. However, low-molecular-weight heparin inhibited giant multinuclear cells formation. At supratherapeutic doses, both low-molecular-weight and unfractionated heparin promoted extravillous trophoblast differentiation. Low-dose aspirin had minimal effects on the extravillous trophoblast differentiation. Both unfractionated and low-molecular-weight heparin inhibited hepatocyte growth factor-stimulated extravillous trophoblast motility at supratherapeutic doses. At a therapeutic dose of 0.25 IU/mL, only unfractionated heparin inhibited hepatocyte growth factor-stimulated motility, whereas low-molecular-weight heparin had no effect. CONCLUSION: Our data suggest that unfractionated and low-molecular-weight heparin have differing effects on trophoblast differentiation and motility at therapeutic doses. This finding may be one of many factors that contribute to the clinical scenario.

Anticoagulants↗
PubMed2004

Immunohistochemical localization of androgen receptors in the urogenital tracts of human embryos.

The aim of this study was to investigate androgen receptor (AR) expression in the developing human urogenital tract. The distribution of AR was examined in paraffin-embedded tissue sections of the lower urogenital tract using 55 human embryos of 8-12 weeks of gestation. Immunohistochemistry was performed for AR detection and gender was determined by polymerized chain reaction. There were no differences in the distribution of AR in male and female embryos at any stage of gestation. AR was present only in the mesenchymal tissues of the urogenital sinus at 8 weeks whilst the epithelium was negative, but after 9 weeks the epithelium also showed progressively more positive staining. In the phallus, AR staining was prominent. There was far less staining in the epithelium of the urethral groove from 8 to 10 weeks, whilst the mesenchyme of the urethral folds showed positive staining. At 11 and 12 weeks, both the urethral groove and folds showed uniform staining. The genital tubercle, genital swelling and bulbourethral gland precusors were also positively stained, although paramesonephric ducts were negative. Staining was observed in the mesonephric duct from 9 weeks. There was an absence of staining in the rectum at all stages of gestation. The expression of AR in an epithelium may be dependent upon the mesenchyme. Mesenchymal-epithelial interactions played an important role in development, as has been described in experimental animals. AR expression could play a part in the growth of the genital organs.

Bulbourethral Glands↗
PubMed2003

Successful pregnancy outcome following 19 consecutive miscarriages: case report.

No cause can be found in 50% of patients with recurrent miscarriage. Recent research has shown that high levels of natural killer (NK) cells within the endometrium may be associated with idiopathic recurrent miscarriage. This case report describes a patient in whom an excessive number of uterine NK cells were found. She received preconceptual prednisolone and delivered a live baby. This is a novel observation of untested significance.

Abortion, Habitual↗
PubMed2003

Activated protein C resistance and pregnancy loss.

Activated protein C resistance is a thrombophilia with an established role in producing thrombosis which more recently has been implicated in the pathogenesis of pregnancy loss. This review will analyse recent literature to evaluate this association and address the gestation and type of pregnancy loss.

Abortion, Spontaneous↗
PubMed2002

Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment.

OBJECTIVE: To compare the efficacy of low-dose aspirin alone versus low-dose aspirin plus low molecular weight heparin in pregnant women with antiphospholipid syndrome and recurrent miscarriage as prophylaxis against pregnancy loss. METHODS: From a regional miscarriage clinic, 119 consecutive women with persistently positive tests for lupus anticoagulant and/or anticardiolipin immunoglobulin G and M antibody were invited to participate in a randomized, controlled trial between 1997 and 2000. After ethical approval and adherence to a written protocol, 12 women were unwilling to participate, five failed exclusion/inclusion criteria, and four were nonpregnant. Laboratory analysis was performed by Sheffield University Coagulation Department, electronically generated randomization by Manchester University Centre for Cancer Epidemiology, and data collection and analysis by a research officer at Leeds University. Viability ultrasound every 2 weeks was provided until 12 weeks' gestation before transfer to the pregnancy support antenatal clinic. RESULTS: Ninety-eight women were randomized before 12 weeks' gestation. Forty-seven received low-dose aspirin 75 mg daily (group A), and 51 received low-dose aspirin plus low molecular weight heparin 5000 U subcutaneously daily (group B) throughout pregnancy. There were 13 pregnancy losses and 34 live births in group A and 11 losses and 40 live births in group B. The live-birth rate was 72% in group A and 78% in group B (odds ratio 1.39, 95% confidence interval 0.55, 3.47). There were no cases of maternal thrombosis in either group. CONCLUSION: A high success rate is achieved when low-dose aspirin is used for antiphospholipid syndrome in pregnancy. The addition of low molecular weight heparin does not significantly improve pregnancy outcome.

Abortion, Spontaneous↗
PubMed2002

Recurrent miscarriage: a defect in nature's quality control?

Recent data on recurrent miscarriage (RM) is discussed in the framework of the selection failure hypothesis which states, 'Recurrent miscarriage is the result of failure of the prevention of 'poor quality' embryos implanting, allowing embryos that are destined to fail to implant and present clinically as recurrent miscarriage. Thus, recurrent miscarriage is a failure of nature's quality control.' The assumption that RM results from the maternal rejection of normal fetuses is challenged and evidence reviewed regarding the contribution of abnormal embryos and endometrial receptivity. Further research is needed to understand the mechanisms of maternal tract-embryo interaction and move towards improved management of recurrent pregnancy loss.

Abortion, Habitual↗