Biomedical subjects

Graham J Burton

Publications and source records attributed to Graham J Burton.

25 records · Page 2Linked to original sources

PubMed2003

Comparison of ultrasonographic and Doppler mapping of the intervillous circulation in normal and abnormal early pregnancies.

OBJECTIVE: To assess the value of ultrasonography and Doppler imaging in characterizing the intervillous circulation in normal and abnormal early pregnancy. DESIGN: Cross-sectional study. SETTING: Tertiary care academic hospital. PATIENT(S): Eighty-five normal pregnancies and 125 missed miscarriages at 7 to 13 weeks of gestation. INTERVENTION(S): Grey-scale ultrasonography was used to evaluate the placental anatomy and detect moving echoes inside the intervillous space, and color power Doppler imaging was used to detect continuous venous-like flow in the placental tissue. MAIN OUTCOME MEASURE(S): Degree of agreement between two investigators for use of grey-scale imaging, comparison of detection of moving echoes in normal and abnormal pregnancies, and comparison of detection of intervillous circulation with grey-scale and color Doppler imaging in abnormal pregnancies. RESULT(S): The overall degree of agreement between the two investigators was good. A significantly different distribution of blood flow was found between normal and abnormal pregnancies at 7 to 9 weeks and 10 to 11 weeks but not at 12 to 13 weeks. Intervillous moving echoes were detected by grey-scale imaging significantly more frequently than an intervillous blood flow was detected with color Doppler imaging. CONCLUSION(S): In early pregnancy failure, there is a premature and diffuse onset of intervillous blood flow that can be detected by grey-scale imaging. This abnormal blood flow pattern may increase the oxidative stress on the early placental tissue and subsequently impair placental development.

Cross-Sectional Studies↗

PubMed2003

Relationship among maternal serum endocrinology, placental karyotype, and intervillous circulation in early pregnancy failure.

OBJECTIVE: To evaluate the relationship among maternal serum endocrinology, placental karyotype, and intervillous blood flow in missed miscarriage. DESIGN: Cross-sectional study of maternal serum, transvaginal ultrasound/Doppler, and placental cytogenetic and immunohistochemical investigations. SETTING: Tertiary care academic hospital. PATIENT(S): One hundred fifty-two women with missed miscarriage between 7 and 13 weeks of gestation. INTERVENTION(S): Ultrasound features, placental intervillous circulation findings on color Doppler imaging, and maternal serum level of alpha-fetoprotein (AFP), beta-hCG, E(2), P, and inhibin A were compared retrospectively with placenta karyotype and hCG immunochemistry. MAIN OUTCOME MEASURES: Data were analyzed according to karyotype results, presence or absence of an intervillous circulation, and delay between fetal demise and evacuation. RESULT(S): The presence of intervillous blood flow and serum concentrations of the different hormones were independent of placental karyotype. Serum beta-hCG and P were significantly higher in cases with intervillous blood flow. No difference in immunostaining for beta-hCG was found between placental tissues from normal pregnancies and missed miscarriages, but significantly higher villous beta-hCG content was found on Western blotting in miscarriage with a recent fetal demise. CONCLUSION(S): The excessive entry of maternal blood inside the placenta in the early stage of most miscarriages is unrelated to conceptus karyotype, and hCG features may reflect a temporary attempt of the trophoblast to stabilize after the initial oxidative insult.

Abortion, Spontaneous↗

PubMed2003

Physiological implications of the materno-fetal oxygen gradient in human early pregnancy.

This study evaluates the role of the fetal fluid cavities on materno-fetal oxygen diffusion in early pregnancy. Oxygen tension (pO2) was recorded using a multiparameter sensor inserted inside the exocoelomic cavity (ECC) or in the amniotic cavity. There was no correlation between coelomic pO(2) and gestational age, but a negative correlation was found between amniotic pO(2) and gestational age. The mean (SEM) pO(2) was 19.5 mm Hg (1.83) in the ECC at 7-11 weeks and 15.4 mm Hg (1.36) in the amniotic cavity at 11-16 weeks. The volume of the ECC changed little between 7 and 10 weeks of gestation, indicating that coelomic pO(2) results from passive oxygen diffusion through the placenta and is an indicator of the overall pO(2) inside the gestational sac during the first trimester. By contrast, the amniotic cavity volume increases exponentially, whereas amniotic pO(2) decreases with gestational age, suggesting that the increase in uterine blood flow is not sufficient to compensate for the rapid increase in amniotic fluid volume during the first half of pregnancy.

Amniotic Fluid↗

PubMed2003

Soluble vascular endothelial growth factor receptor 1 inhibits edema and epithelial proliferation induced by 17beta-estradiol in the mouse uterus.

The uterine response to 17beta-estradiol (E2) includes increased water retention, enhanced vascular permeability, DNA and RNA synthesis, and increased cellular mitosis. We have used the natural antagonist of vascular endothelial growth factor A (VEGF-A), sflt-1 (soluble form of flt-1), to determine whether the edematous and proliferative effects of E2 in the uterus are mediated by VEGF-A. Female BALB/c mice were ovariectomized and treated with E2 (10 micro g/kg) in the absence or presence of sflt-1 (0.8 and 4.0 mg/kg) for 24 h. E2 induced increases in uterine mass from 25.3 to 36.8 mg, in total cross-sectional uterine area from 771 to 1133 micro m(2), in cross-sectional endometrial area from 268 to 569 micro m(2), and in the mitotic index of lumenal epithelial cells from 0% to 53%. Antagonism with sflt-1 reduced the E2-induced increases in total uterine area to 779 micro m(2), endometrial area to 398 micro m(2) and the mitotic index of lumenal epithelial cells to 25%, but the E2-induced increase in uterine mass was not significantly reduced. From these data we conclude that the edematous response and proliferation of lumenal epithelial cells in the murine uterus are mediated in part through VEGF-A. These data suggest that sflt-1 could be a useful anti-VEGF-A agent and may be effective in modifying uterine biology.

Animals↗

PubMed2002

Hypoxia-reoxygenation: a potent inducer of apoptotic changes in the human placenta and possible etiological factor in preeclampsia.

Preeclampsia is a severe disorder of human pregnancy characterized by generalized activation of maternal endothelial cells. Oxidative stress of the placenta is considered a key intermediary step, precipitating deportation of apoptotic fragments into the maternal circulation, but the cause remains unknown. We hypothesize that intermittent placental perfusion, secondary to deficient trophoblast invasion of the endometrial arteries, leads to an ischemia-reperfusion-type insult. We therefore tested whether hypoxia-reoxygenation (H/R) in vitro stimulates apoptosis in human placental tissues compared with controls kept hypoxic or normoxic throughout. After H/R, release of cytochrome c from mitochondria was significantly increased and was associated with intense immunolabeling for active caspase 3 in the syncytiotrophoblast and fetal endothelial cells. There was also increased labeling of syncytiotrophoblastic nuclei for cleaved poly (ADP-ribose) polymerase (PARP), and higher cytosolic concentrations of cleaved PARP fragment were detected by Western blot. Syncytiotrophoblastic nuclei displayed increased chromatin condensation, and a significantly greater percentage was TUNEL positive. These changes were accompanied by increased lactate dehydrogenase release into the medium. Preadministration of the free radical scavenger, desferrioxamine, reduced cytochrome c release and the TUNEL-positive index, suggesting generation of hydroxyl radicals mediates these processes. By contrast, hypoxia alone caused a smaller increase in the TUNEL-positive index, and the majority of syncytiotrophoblastic nuclei displayed karyolysis, whereas normoxic controls remained euchromatic. We conclude that H/R stimulates apoptotic changes within the syncytiotrophoblast, whereas hypoxia principally induces necrosis. The quality of placental perfusion may therefore be a more important factor in the pathophysiology of preeclampsia than the absolute quantity.

Apoptosis↗

PubMed2002

Uterine glands provide histiotrophic nutrition for the human fetus during the first trimester of pregnancy.

Providing adequate nutrition to the fetus is key to a successful pregnancy. The interstitial form of implantation displayed by the human blastocyst is generally associated with early onset of maternal blood flow to the developing placenta, and hence hemotrophic exchange. However, the recent finding that the maternal intraplacental circulation is not fully established until the third month of gestation suggests that human fetal nutrition may be initially histiotrophic. We therefore investigated activity of the uterine glands during early pregnancy. We demonstrate here that these glands remain active until at least wk 10 of pregnancy, and that their secretions are delivered freely into the placental intervillous space. We also demonstrate phagocytic uptake by the placental syncytiotrophoblast of two glycoproteins, the mucin MUC-1 and glycodelin A, synthesized in the maternal glands. Glycodelin was also detected within the epithelium of the secondary yolk sac lining the exocoelomic cavity, indicating that the yolk sac may play an important role in nutrient exchange before vascularisation of the chorionic villi. Our findings demonstrate that the uterine glands are an important source of nutrients during organogenesis, when metabolism is essentially anaerobic.

Endocrine System↗

PubMedDate not supplied

Oxygen, early embryonic metabolism and free radical-mediated embryopathies.

Free radicals, once the preserve of chemists, are now recognized as playing a central role in many biological systems. They are formed as an inevitable by-product of aerobic respiration and various cytoplasmic processes at a rate dependent upon the prevailing oxygen tension. At physiological concentrations, oxygen and nitrogen free radical species play key roles in intracellular signalling, regulating many homeostatic mechanisms and mediating stress responses. If concentrations exceed cellular defences, however, then indiscriminate damage may occur to lipids, proteins and DNA. Cell function may be perturbed, and in the most severe cases apoptosis may result. Although there are significant species differences, many aspects of early mammalian development, from fertilization through to differentiation of the principal organ systems, take place in vivo in a low oxygen environment. This may serve to protect the embryo from free radical damage, for exposure of early embryos to ambient oxygen concentrations or the products of maternal metabolic disorders is often associated with reduced viability and an increased rate of congenital malformations. Administration of free radical scavengers, including vitamins C and E, can mitigate many of these effects, indicating the importance of a balanced maternal diet to successful reproduction.

Calcium↗