Birthweight –BMI or glucose. a human in vivo study

Autor: Maia Blomhoff Holm, Tore Henriksen, Guttorm Haugen, Gun Lisbet Opheim, Ane Moe Holme, Trond M. Michelsen
Rok vydání: 2014
Předmět:
Zdroj: Placenta. 35:A68
ISSN: 0143-4004
DOI: 10.1016/j.placenta.2014.06.220
Popis: s / Placenta 35 (2014) A1eA112 A68 Background: The presence of antiphospholipid antibodies (aPL) in the maternal circulation is a strong risk factor for preeclampsia, however the underlying mechanism is not known. Antiphospholipid antibodies are internalised into the human syncytiotrophoblast via an antigen-dependent, receptor-mediated process. Once inside the syncytiotrophoblast, aPL cause aberrant cell death leading to the extrusion of increased amounts of necrotic trophoblast debris into the maternal blood, which is believed to cause endothelial cell dysfunction and contribute to the pathogenesis of preeclampsia. Objective: To identify candidate metabolites that could link aPL to trophoblast cell death, using an unbiased metabolomics approach. Methods: First and third trimester human placental explants were cultured with aPL, a control antibody, or media only, and the placental metabolic footprints (conditioned culture media) of the explants were examined by mass spectroscopy. Molecular targets of metabolites of interest were investigated using qRTPCR and immunohistochemistry. Results: The levels of 79 (first trimester explants) and 132 metabolites (third trimester explants) were altered in response to treatment with aPL. These metabolites included ceramides and diacylglycerols, which play important roles in cell death regulatory pathways. Antiphospholipid antibodies also decreased the expression of protein kinase C-epsilon (PRKCE) in placental explants, a response that may be a result of the disrupted balance between ceramides and diacylglycerols caused by aPL. Conclusion: These data suggest that one mechanism by which aPL cause aberrant cell death in the syncytiotrophoblast is by disruption of placental lipid signalling, which may influence the placental expression of PRKCE, a key molecular regulator of cell life and death. Alterations in syncytiotrophoblast death mechanisms could lead to the extrusion of necrotic trophoblast debris, triggering endothelial dysfunction, a hallmark feature of preeclampsia. P2.21-N. BIRTHWEIGHT eBMI OR GLUCOSE. A HUMAN IN VIVO STUDY Ane Moe Holme , Trond M. Michelsen , Maia Blomhoff Holm , Gun Lisbet Opheim , Guttorm Haugen , Tore Henriksen a,b Oslo University Hospital, Department of Obstetrics, Oslo, Norway; University of Oslo, Oslo, Norway Background: Maternal BMI is a robust determinant of birthweight, also after adjusting for maternal glucose. The mechanism by which BMI affects fetal growth is largely unknown. We asked whether it may alter fetal glucose metabolism, and studied associations between maternal BMI and birthweight, uteroplacental glucose supply through the umbilical vein (fetal supply) and fetal glucose consumption (mmol/min). Methods: A cross-sectional study of 98 fasting women with uncomplicated pregnancies undergoing planned caesarean section at Oslo University Hospital. We obtained blood samples from the radial artery, the umbilical artery (UA) and vein (UV) during delivery. We measured internal vessel diameter (D) and time-averaged maximum velocity (TAMX) in the intra-abdominal UV by ultrasound at the day of delivery (n1⁄468). Blood flow (Q) 1⁄4 0.5$(D/ 2)2$p$TAMX. Fetal glucose supply and consumption were calculated by multiplying Q by the glucose concentration in the UV and the UV-UA glucose difference, respectively. Results:Mean (SD) UV flowwas 198.3 (81.1) ml/min and mean UV glucose concentrationwas 3.93 (0.47) mmol/L, giving a fetal glucose supply of 0.79 (0.36) mmol/min. Glucose concentration in the UAwas 3.37 (0.47) mmol/L. Paired t-test showed a significant fetal glucose consumption of 0.11 (0.11) mmol/min, p
Databáze: OpenAIRE
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