{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST001448","ANALYSIS_ID":"AN002419","VERSION":"1","CREATED_ON":"August 20, 2020, 11:40 am"},

"PROJECT":{"PROJECT_TITLE":"Maternal Hypercortisolemia alters placental metabolism","PROJECT_SUMMARY":"Previous studies have suggested that increases in maternal cortisol or maternal stress in late pregnancy increase the risk of stillbirth at term. In an ovine model with increased maternal cortisol over the last 0.20 of gestation, we have previously found evidence of disruption of fetal serum and cardiac metabolomics, and altered expression of genes related to mitochondrial function and metabolism in biceps femoris, diaphragm and cardiac muscle. The present studies were designed to test for effects of chronically increased maternal cortisol on gene expression and metabolomics in placentomes near term. We hypothesized that changes in placenta may underlie or contribute to the alterations in fetal serum metabolomics, and thereby contribute to changes in striated muscle metabolism. Placentomes were collected from pregnancies in early labor (143±1 d gestation) of control ewes (n=7) or ewes treated with cortisol (1 mg/kg/d iv; n=5) starting at day 115 of gestation. Transcriptomics and metabolomics were performed using an ovine gene expression microarray (Agilent 019921) and HR-MAS NMR, respectively. Multi-omic analysis indicates that amino acid metabolism, particularly of branched chain amino acids and glutamate occur in placenta; changes in amino acid metabolism, degradation or biosynthesis in placenta were consistent with changes in valine, isoleucine, leucine and glycine in fetal serum. The analysis also indicates changes in glycerophospholipid metabolism and suggests changes in ER stress and antioxidant status in the placenta. These findings suggest that changes in placental function occurring with excess maternal cortisol in late gestation may contribute to metabolic dysfunction at birth.","INSTITUTE":"University of Florida","DEPARTMENT":"Pharmacodynamics","LAST_NAME":"Keller-Wood","FIRST_NAME":"Maureen","ADDRESS":"1345 SW Archer Rd, PO 100487, Gainesville, FL 32610","EMAIL":"kellerwd@cop.ufl.edu","PHONE":"352-273-7687"},

"STUDY":{"STUDY_TITLE":"Maternal Hypercortisolemia alters placental metabolism: NMR metabolomics","STUDY_SUMMARY":"NMR metabolomic studies of placental tissue from sheep with excess maternal cortisol during late gestation","INSTITUTE":"University of Florida","LAST_NAME":"Walejko","FIRST_NAME":"Jacquelyn","ADDRESS":"300 N Duke St Durham NC 27701","EMAIL":"jacquelyn.walejko@duke.edu","PHONE":"9194792304"},

"SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Ovis aries","TAXONOMY_ID":"9940"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"656",
"Factors":{"Treatment":"Cortisol","Sex":"Female"},
"Additional sample data":{"RAW_FILE_NAME":"1"}
},
{
"Subject ID":"-",
"Sample ID":"784",
"Factors":{"Treatment":"Control","Sex":"Male"},
"Additional sample data":{"RAW_FILE_NAME":"3"}
},
{
"Subject ID":"-",
"Sample ID":"665",
"Factors":{"Treatment":"Cortisol","Sex":"Female"},
"Additional sample data":{"RAW_FILE_NAME":"5"}
},
{
"Subject ID":"-",
"Sample ID":"749",
"Factors":{"Treatment":"Control","Sex":"Female"},
"Additional sample data":{"RAW_FILE_NAME":"6"}
},
{
"Subject ID":"-",
"Sample ID":"521",
"Factors":{"Treatment":"Control","Sex":"Male"},
"Additional sample data":{"RAW_FILE_NAME":"7"}
},
{
"Subject ID":"-",
"Sample ID":"874",
"Factors":{"Treatment":"Cortisol","Sex":"Female"},
"Additional sample data":{"RAW_FILE_NAME":"8"}
},
{
"Subject ID":"-",
"Sample ID":"993A",
"Factors":{"Treatment":"Control","Sex":"Male"},
"Additional sample data":{"RAW_FILE_NAME":"9"}
},
{
"Subject ID":"-",
"Sample ID":"713",
"Factors":{"Treatment":"Cortisol","Sex":"Female"},
"Additional sample data":{"RAW_FILE_NAME":"10"}
},
{
"Subject ID":"-",
"Sample ID":"993B",
"Factors":{"Treatment":"Control","Sex":"Female"},
"Additional sample data":{"RAW_FILE_NAME":"11"}
},
{
"Subject ID":"-",
"Sample ID":"568",
"Factors":{"Treatment":"Control","Sex":"Female"},
"Additional sample data":{"RAW_FILE_NAME":"12"}
},
{
"Subject ID":"-",
"Sample ID":"594",
"Factors":{"Treatment":"Control","Sex":"Male"},
"Additional sample data":{"RAW_FILE_NAME":"13"}
},
{
"Subject ID":"-",
"Sample ID":"768",
"Factors":{"Treatment":"Cortisol","Sex":"Female"},
"Additional sample data":{"RAW_FILE_NAME":"14"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Placentomes were collected at necropsy from control ewes and ewes treated with cortisol (CORT: 1mg/kg/d from day 115 of pregnancy) at days 141-144 of gestation. CORT ewes received an intravenous infusion of cortisol (Solu-Cortef, hydrocortisone sodium succinate in sodium phosphate; Pfizer, New York, NY); control animals did not receive any treatment. Animals were sacrificed for collection of tissues at the first signs of labor, as evidenced by changes in uterine blood flow; placentomes were collected from sheep in early stages of labor at between 141-144 days and 142-144 days of gestation in the cortisol-treated and control groups, respectively. In this cohort of ewes, there were 7 control ewes, of which data were collected from placentomes of 7 live fetuses (including one set of twins); there was one lamb born, and that placenta was not collected. In this cohort there were 11 cortisol- treated ewes, from which we collected placentomes from 5 live fetuses. There was one live lamb born, and 5 stillborn lambs, from which placentas were not collected. Placentomes were classified as A-D placentomes, snap frozen in liquid nitrogen, and stored in -80C until metabolomic analysis.","SAMPLE_TYPE":"Placenta"},

"TREATMENT":{"TREATMENT_SUMMARY":"Placentomes were collected at necropsy from control ewes and ewes treated with cortisol (CORT: 1mg/kg/d from day 115 of pregnancy) at days 141-144 of gestation. CORT ewes received an intravenous infusion of cortisol (Solu-Cortef, hydrocortisone sodium succinate in sodium phosphate; Pfizer, New York, NY); control animals did not receive any treatment."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"High-resolution magic angle spinning (HR-MAS) proton nuclear magnetic resonance (1H-NMR) was used to determine metabolites present in placental tissue. Briefly, 30 μL of deuterium oxide (D2O) with 3.3 mM 3-(Trimethylsilyl)-1-propanesulfonic acid (DSS) as a reference standard was added to 27.7-52.1 mg (mean 35.3 mg) of placental tissue before being placed into a 4 mm HR-MAS rotor (Bruker Biospin) and spun at 6 kHz with a spectral width of 10 ppm. Data were acquired on an Avance III 600 MHz Bruker NMR spectrometer equipped with a 4 mm HR-MAS probe at the University of Georgia Complex Carbohydrate Research Center. Data were acquired using a one-dimensional experiment with T2 filter using Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence with water presaturation (CPMGPR1D)."},

"ANALYSIS":{"ANALYSIS_TYPE":"NMR"},

"NM":{"INSTRUMENT_NAME":"Bruker Avance III HD","INSTRUMENT_TYPE":"FT-NMR","NMR_EXPERIMENT_TYPE":"1D-1H","SPECTROMETER_FREQUENCY":"600 MHz"},

"NMR_METABOLITE_DATA":{
"Units":"Area Under Curve",

"Data":[{"Metabolite":"Lipid (-CH3)","656":"2.242389176","665":"3.809119519","874":"3.950549632","713":"3.396744874","768":"3.655016682","784":"4.138817585","749":"4.25989936","521":"3.514435259","993A":"4.55458362","993B":"3.268513682","568":"3.538174986","594":"2.633201729"},{"Metabolite":"Leucine","656":"4.299739627","665":"2.285780203","874":"2.565743146","713":"2.577903522","768":"2.180277276","784":"2.263470942","749":"2.311929583","521":"1.931117806","993A":"2.311563857","993B":"2.931377311","568":"1.832554758","594":"2.273570102"},{"Metabolite":"Isoleucine","656":"0.794372466","665":"0.454519294","874":"0.437997067","713":"0.49692665","768":"0.401696967","784":"0.432044676","749":"0.43948745","521":"0.330387715","993A":"0.442449931","993B":"0.540842677","568":"0.348272318","594":"0.428864983"},{"Metabolite":"Valine","656":"1.37102458","665":"0.595426446","874":"0.732510268","713":"0.673351146","768":"0.539095761","784":"0.542604821","749":"0.605476821","521":"0.444890302","993A":"0.595956857","993B":"0.851294909","568":"0.476916156","594":"0.616046206"},{"Metabolite":"Lipid (-CH)","656":"2.151627931","665":"7.618917475","874":"7.198638109","713":"5.03204128","768":"5.97616203","784":"6.957224374","749":"8.189074535","521":"5.494842384","993A":"8.752739029","993B":"5.207249128","568":"6.643386518","594":"4.185869228"},{"Metabolite":"Alanine","656":"2.345442355","665":"1.644259554","874":"1.597410534","713":"2.01311568","768":"1.559373932","784":"1.706268296","749":"1.807180903","521":"1.287549471","993A":"1.669190904","993B":"2.030010551","568":"1.754121876","594":"1.6439098"},{"Metabolite":"Lipid (Beta-CH2)","656":"0.744009241","665":"1.140799275","874":"1.183847165","713":"0.742519474","768":"0.991843252","784":"1.181927832","749":"1.427785203","521":"0.667738618","993A":"1.184395545","993B":"1.013666337","568":"1.324415431","594":"0.792787305"},{"Metabolite":"Acetate","656":"0.659579979","665":"0.494082232","874":"0.400918887","713":"0.391565064","768":"0.45627498","784":"0.470601668","749":"0.478647967","521":"0.37631367","993A":"0.480458385","993B":"0.633795247","568":"0.484801557","594":"0.434949441"},{"Metabolite":"Glutamate","656":"1.277005783","665":"1.00378418","874":"0.768801494","713":"0.782834966","768":"0.895942788","784":"1.285719377","749":"1.098331256","521":"0.991273294","993A":"1.039629152","993B":"1.451644542","568":"1.141807501","594":"1.163723643"},{"Metabolite":"Glutamine","656":"0.418230197","665":"0.372575265","874":"0.264231756","713":"0.21465936","768":"0.348815321","784":"0.549392019","749":"0.51483962","521":"0.21620621","993A":"0.331322904","993B":"0.5745901","568":"0.391412043","594":"0.378787836"},{"Metabolite":"Glutathione","656":"0.193648648","665":"0.217998595","874":"0.183238029","713":"0.105833648","768":"0.171155398","784":"0.356070925","749":"0.250237334","521":"0.1991357","993A":"0.222959112","993B":"0.316220518","568":"0.226829608","594":"0.331995569"},{"Metabolite":"Methionine","656":"0.026302857","665":"0.019267512","874":"0.014984792","713":"0.008334918","768":"0.007607154","784":"0.038558538","749":"0.04093619","521":"-0.026593911","993A":"0.006017306","993B":"0.05254543","568":"0.021600042","594":"0.051010083"},{"Metabolite":"Aspartate","656":"0.03904523","665":"0.094370031","874":"0.126118128","713":"0.068019275","768":"0.1017084","784":"0.057611096","749":"0.106786565","521":"0.025635939","993A":"0.098884719","993B":"0.062016138","568":"0.112649903","594":"0.093672828"},{"Metabolite":"Asparagine","656":"0.277818685","665":"0.157796407","874":"0.394412548","713":"0.220016148","768":"0.26643748","784":"0.35146956","749":"0.319615787","521":"0.301808355","993A":"0.196738036","993B":"0.325908917","568":"0.329475948","594":"0.452363009"},{"Metabolite":"Lysine","656":"0.458273233","665":"0.195481383","874":"0.361293805","713":"0.321635425","768":"0.31668478","784":"0.428887475","749":"0.412711996","521":"0.310095938","993A":"0.213878465","993B":"0.44492525","568":"0.343061966","594":"0.454891857"},{"Metabolite":"Creatine","656":"0.247824619","665":"0.122777032","874":"0.192405855","713":"0.227370258","768":"0.195691824","784":"0.230859314","749":"0.212638688","521":"0.298822066","993A":"0.170363881","993B":"0.260054776","568":"0.236886705","594":"0.309058819"},{"Metabolite":"Citrulline","656":"0.173371345","665":"0.079198602","874":"0.155735177","713":"0.182221461","768":"0.166235472","784":"0.187712744","749":"0.17835926","521":"0.216001999","993A":"0.095668788","993B":"0.176071225","568":"0.200864364","594":"0.192748351"},{"Metabolite":"Ethanolamine","656":"0.244289509","665":"0.089812417","874":"0.252444042","713":"0.206457973","768":"0.236097441","784":"0.28122313","749":"0.38891794","521":"0.290953595","993A":"0.191569078","993B":"0.310790184","568":"0.472176639","594":"0.322156624"},{"Metabolite":"Choline/Phosphocholine","656":"0.618561466","665":"0.541288363","874":"0.703739064","713":"0.974814614","768":"1.159084115","784":"0.975135935","749":"0.934245546","521":"1.24277794","993A":"1.126000719","993B":"1.30116655","568":"1.269952513","594":"0.783616129"},{"Metabolite":"Glycerophosphocholine","656":"2.443749854","665":"3.219526726","874":"3.970876212","713":"3.52611345","768":"4.76797191","784":"4.453432287","749":"3.920177866","521":"5.464910377","993A":"3.074437278","993B":"3.316314477","568":"3.69046827","594":"3.074642108"},{"Metabolite":"Proline","656":"0.048447217","665":"0.049735477","874":"0.047445648","713":"0.05128176","768":"0.044542256","784":"0.05288908","749":"0.055253819","521":"0.063343132","993A":"0.045499847","993B":"0.057211642","568":"0.040695459","594":"0.059964736"},{"Metabolite":"Taurine","656":"0.749618285","665":"0.675089376","874":"0.754965567","713":"1.038565829","768":"0.675809754","784":"0.817921033","749":"0.698680329","521":"1.303274826","993A":"0.882079174","993B":"0.878619167","568":"0.860958332","594":"1.1332409"},{"Metabolite":"Glycine","656":"1.683605721","665":"1.870524114","874":"1.784684872","713":"2.097562025","768":"2.350489154","784":"2.159715145","749":"2.042294406","521":"2.610485925","993A":"2.46699209","993B":"2.162102118","568":"2.208831717","594":"1.950770385"},{"Metabolite":"Glycerol","656":"0.231278767","665":"0.162129213","874":"0.208723823","713":"0.22050995","768":"0.179615066","784":"0.148876694","749":"0.193345036","521":"0.233249231","993A":"0.187360323","993B":"0.166565049","568":"0.180569094","594":"0.206557889"},{"Metabolite":"Betaine","656":"0.613755433","665":"0.829675526","874":"0.627234326","713":"0.837961731","768":"0.811402286","784":"0.736253166","749":"0.485531011","521":"0.828994216","993A":"0.683175418","993B":"0.593758057","568":"0.613635743","594":"0.5880968"},{"Metabolite":"Serine","656":"0.852330779","665":"0.655197443","874":"0.623871014","713":"0.800257822","768":"0.618749534","784":"0.597283499","749":"0.564267224","521":"0.755890194","993A":"0.643671595","993B":"0.703642742","568":"0.658714893","594":"0.751270317"},{"Metabolite":"Myo-inositol","656":"0.844819633","665":"0.872252606","874":"0.804992851","713":"1.00412676","768":"0.919143422","784":"0.78846167","749":"0.761147692","521":"1.036530071","993A":"1.126417223","993B":"1.017673907","568":"0.938111878","594":"0.867510265"},{"Metabolite":"Lactate","656":"2.732545944","665":"2.429187895","874":"2.561082699","713":"4.471084327","768":"2.425466251","784":"2.407846583","749":"2.505302188","521":"2.66403392","993A":"2.982596509","993B":"2.785578646","568":"2.416090008","594":"2.904588835"},{"Metabolite":"Phosphorylcholine","656":"1.341951725","665":"2.195885888","874":"1.706068139","713":"1.585747377","768":"2.04107288","784":"1.874164685","749":"1.729538573","521":"2.116383272","993A":"1.751710247","993B":"1.555504842","568":"1.534353621","594":"1.316810155"},{"Metabolite":"Threonine","656":"0.661472796","665":"0.656890868","874":"0.73883513","713":"0.64251404","768":"0.625810738","784":"0.629719395","749":"0.757254297","521":"0.682132627","993A":"0.575230119","993B":"0.613952441","568":"0.617802723","594":"0.643376618"},{"Metabolite":"Ascorbate","656":"0.227792617","665":"0.295165904","874":"0.261258425","713":"0.253565982","768":"0.23520622","784":"0.320598814","749":"0.287114603","521":"0.410699774","993A":"0.299950677","993B":"0.263006707","568":"0.281428084","594":"0.324791655"},{"Metabolite":"Lipid (-CH=CH-)","656":"0.493439074","665":"1.698877297","874":"2.391124903","713":"1.260792208","768":"1.739888775","784":"2.10193387","749":"2.373382","521":"1.576506138","993A":"2.71863695","993B":"1.518887431","568":"2.341554524","594":"1.202448307"},{"Metabolite":"Fumarate","656":"0.003642458","665":"-0.00175148","874":"0.003298625","713":"0.008688803","768":"0.003924634","784":"0.002146943","749":"0.001617812","521":"0.008953854","993A":"0.004843811","993B":"0.005215251","568":"0.00500807","594":"0.009014798"},{"Metabolite":"1-Methyhistidine/Histidine","656":"0.049217533","665":"0.105155526","874":"0.019304743","713":"0.083801019","768":"0.125307956","784":"0.034629361","749":"-0.000826305","521":"0.037518108","993A":"0.058383749","993B":"0.054295987","568":"0.018788935","594":"0.039356566"},{"Metabolite":"Tyrosine","656":"0.152698368","665":"0.111743917","874":"0.121381889","713":"0.113832298","768":"0.090401946","784":"0.100100729","749":"0.136878418","521":"0.089862116","993A":"0.0935251","993B":"0.167243113","568":"0.064844048","594":"0.162604109"},{"Metabolite":"Phenylalanine","656":"0.752031727","665":"0.415012303","874":"0.40537087","713":"0.429767729","768":"0.390555387","784":"0.469763181","749":"0.486214106","521":"0.269391831","993A":"0.399798635","993B":"0.776721862","568":"0.325755725","594":"0.541910383"},{"Metabolite":"Uracil","656":"0.043676492","665":"0.038968046","874":"0.028400809","713":"0.040002165","768":"0.04911261","784":"0.04189195","749":"0.045324677","521":"0.036725013","993A":"0.05526046","993B":"0.060442039","568":"0.042148192","594":"0.043800303"},{"Metabolite":"Inosine","656":"0.123765307","665":"0.175609736","874":"0.186814852","713":"0.146646264","768":"0.135934711","784":"0.175452827","749":"0.152331892","521":"0.242812743","993A":"0.166712098","993B":"0.126423522","568":"0.176440428","594":"0.210683636"}],

"Metabolites":[{"Metabolite":"Lipid (-CH3)","PubChem":"-","KEGG":"-"},{"Metabolite":"Leucine","PubChem":"6106","KEGG":"C00123"},{"Metabolite":"Isoleucine","PubChem":"6306","KEGG":"C00407"},{"Metabolite":"Valine","PubChem":"6287","KEGG":"C00183"},{"Metabolite":"Lipid (-CH)","PubChem":"-","KEGG":"-"},{"Metabolite":"Alanine","PubChem":"5950","KEGG":"C00041"},{"Metabolite":"Lipid (Beta-CH2)","PubChem":"-","KEGG":"-"},{"Metabolite":"Acetate","PubChem":"176","KEGG":"C00033"},{"Metabolite":"Glutamate","PubChem":"33032","KEGG":"C00025"},{"Metabolite":"Glutamine","PubChem":"5961","KEGG":"C00064"},{"Metabolite":"Glutathione","PubChem":"3353","KEGG":"C00051"},{"Metabolite":"Methionine","PubChem":"6137","KEGG":"C00073"},{"Metabolite":"Aspartate","PubChem":"5960","KEGG":"C00049"},{"Metabolite":"Asparagine","PubChem":"6267","KEGG":"C00152"},{"Metabolite":"Lysine","PubChem":"5962","KEGG":"C00047"},{"Metabolite":"Creatine","PubChem":"586","KEGG":"C00300"},{"Metabolite":"Citrulline","PubChem":"9750","KEGG":"C00327"},{"Metabolite":"Ethanolamine","PubChem":"700","KEGG":"C00189"},{"Metabolite":"Choline/Phosphocholine","PubChem":"305/1014","KEGG":"C00114/C00588"},{"Metabolite":"Glycerophosphocholine","PubChem":"71920","KEGG":"C00670"},{"Metabolite":"Proline","PubChem":"145742","KEGG":"C00148"},{"Metabolite":"Taurine","PubChem":"1123","KEGG":"C00245"},{"Metabolite":"Glycine","PubChem":"750","KEGG":"C00037"},{"Metabolite":"Glycerol","PubChem":"753","KEGG":"C00116"},{"Metabolite":"Betaine","PubChem":"247","KEGG":"C00719"},{"Metabolite":"Serine","PubChem":"3982","KEGG":"C00716"},{"Metabolite":"Myo-inositol","PubChem":"-","KEGG":"C00137"},{"Metabolite":"Lactate","PubChem":"107689","KEGG":"C00256"},{"Metabolite":"Phosphorylcholine","PubChem":"1014","KEGG":"C00588"},{"Metabolite":"Threonine","PubChem":"6288","KEGG":"C00188"},{"Metabolite":"Ascorbate","PubChem":"3372","KEGG":"C00072"},{"Metabolite":"Lipid (-CH=CH-)","PubChem":"-","KEGG":"-"},{"Metabolite":"Fumarate","PubChem":"444972","KEGG":"C00122"},{"Metabolite":"1-Methyhistidine/Histidine","PubChem":"92105/6274","KEGG":"C01152/C00135"},{"Metabolite":"Tyrosine","PubChem":"6057","KEGG":"C00082"},{"Metabolite":"Phenylalanine","PubChem":"6140","KEGG":"C00079"},{"Metabolite":"Uracil","PubChem":"1174","KEGG":"C00106"},{"Metabolite":"Inosine","PubChem":"135398641","KEGG":"-"}]
}

}