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Metabolomic Profiling in Early Pregnancy using Pre-Diagnostic Sera from Women Who Developed Placental Abruption

ABSTRACT: Placental abruption (PA) is an ischemic placental disorder that results from the premature separation of the placenta from the wall of the uterus before delivery of the fetus. This disorder is associated with pre-term delivery, fetal death, maternal hemorrhagic shock, and renal failure. Several physiologic disturbances, such as oxidative stress, carbohydrate/fatty acid metabolism, and mitochondrial dysfunction, have been associated with ischemic placental disorder as well as with placental abruption. This preliminary study proposes to identify metabolites associated with incident placental abruption using existing serum and clinical data from a previously studied cohort. Metabolomics analysis will be carried out on maternal serum (51 cases and 51 controls) collected in early pregnancy (early second trimester).

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

DISEASE(S): Placental Abruption

SUBMITTER: Jason Burgess

PROVIDER: ST000405 | MetabolomicsWorkbench | Fri May 27 00:00:00 BST 2016

REPOSITORIES: MetabolomicsWorkbench

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Project description:We used the rhesus monkey (Macaca mulatta) as our animal model for the current study with two goals: to characterize the changes in histology and gene expression from early to late gestation (prenatal uterine organogenesis) and to determine if there are effects of prenatal exposure to bisphenol A (BPA) on the developing female uterus. Pregnant rhesus monkeys carrying a female fetus (N=22) were divided into two experimental groups, based on gestational timing: 'early' (N=10) and 'late' (N=12). These groups were then equally sub-divided into control (unexposed) and BPA (exposed) groups (5 Early Control, 5 Early BPA-exposed, 6 Late Control and 6 Late BPA-exposed.) The BPA-exposed monkeys received a deuterated BPA (dBPA, CDN Isotopes, Quebec, Canada) fruit treat on a daily basis, at a dose of 400ug/kg/day). The dosing was aimed at achieving serum levels of BPA detected in adult human biomonitoring studies. The control animals received a vehicle control on a daily basis. The 'early' time period (mid-gestation) referred to gestational days 50-100, approximating the second trimester of human gestation. The fetal monkeys in the 'early' group were delivered via cesarean section on gestation day 100 and euthanized. Samples of maternal and fetal blood and amniotic fluid were obtained. Maternal and fetal weights were also recorded. The 'late' time period referred to gestational days 100-165, approximating the third trimester of human gestation. The fetal monkeys in the 'late' group were delivered vaginally and euthanized. There were five idiopathic stillbirths (2 Control, 3 BPA-exposed) in the late group. Samples of maternal and fetal blood and amniotic fluid were obtained. Maternal and fetal weights were also recorded. After delivery, the fetal uterus was excised and cut sagitally from fundus to cervix; one side was fixed for histological evaluation and the other half was frozen for analysis of gene expression by microarray. The stillbirths were excluded from the microarray.

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Metabolomic Profiling in Early Pregnancy using Pre-Diagnostic Sera from Women Who Developed Placental Abruption

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