Summary of Study ST003213
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002004. The data can be accessed directly via it's Project DOI: 10.21228/M8K819 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003213 |
| Study Title | The central role of creatine and polyamines in fetal growth restriction |
| Study Summary | Placental insufficiency is often associated with fetal growth restriction (FGR), a condition associated with both short- and long-term complications for newborns. In this study, we performed a comprehensive transcriptomic and metabolomic characterization of the placenta of newborns born small for gestational age (SGA) and appropriate for gestational age (AGA). Transcriptome and metabolome data obtained from villous tissue biopsies and verified in 3D trophoblast organoids revealed that the defective placentas associated with FGR are characterized by metabolic reprogramming consisting of adaptation to hypoxia and alteration of arginine metabolism, particularly at the level of synthesis of polyamines and creatine phosphate. Arginine was utilized in defective SGA placentas to synthesize phosphocreatine, an energy-rich compound that is critical for ATP production and represents a positive metabolic adaptation that supports trophoblast fitness. In addition, SGA placentas were characterized by a deficit in polyamines due to overexpression of SAT1. SAT1 catalyzes the acetylation of spermine and spermidine and promotes their excretion from the trophoblast, resulting in a deficit of polyamines that cannot be compensated by arginine or polyamine supplementation unless SAT1 expression is disrupted. In conclusion, our study improves the understanding of metabolic adaptations associated with placental dysfunction and provides valuable insights for future therapeutic interventions |
| Institute | University of Udine |
| Last Name | Di Giorgio |
| First Name | Eros |
| Address | piazzale Kolbe 4, Udine, Italy, 33100, Italy |
| eros.digiorgio@uniud.it | |
| Phone | 0432494338 |
| Submit Date | 2024-04-22 |
| Num Groups | 2 |
| Total Subjects | 6 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-04-21 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002004 |
| Project DOI: | doi: 10.21228/M8K819 |
| Project Title: | The central role of creatine and polyamines in fetal growth restriction |
| Project Summary: | Placental insufficiency is often associated with fetal growth restriction (FGR), a condition associated with both short- and long-term complications for newborns. In this study, we performed a comprehensive transcriptomic and metabolomic characterization of the placenta of newborns born small for gestational age (SGA) and appropriate for gestational age (AGA). Transcriptome and metabolome data obtained from villous tissue biopsies and verified in 3D trophoblast organoids revealed that the defective placentas associated with FGR are characterized by metabolic reprogramming consisting of adaptation to hypoxia and alteration of arginine metabolism, particularly at the level of synthesis of polyamines and creatine phosphate. Arginine was utilized in defective SGA placentas to synthesize phosphocreatine, an energy-rich compound that is critical for ATP production and represents a positive metabolic adaptation that supports trophoblast fitness. In addition, SGA placentas were characterized by a deficit in polyamines due to overexpression of SAT1. SAT1 catalyzes the acetylation of spermine and spermidine and promotes their excretion from the trophoblast, resulting in a deficit of polyamines that cannot be compensated by arginine or polyamine supplementation unless SAT1 expression is disrupted. In conclusion, our study improves the understanding of metabolic adaptations associated with placental dysfunction and provides valuable insights for future therapeutic interventions. |
| Institute: | University of Udine |
| Department: | Medicine |
| Laboratory: | Biochemistry |
| Last Name: | Di Giorgio |
| First Name: | Eros |
| Address: | piazzale Kolbe 4, Udine, Italy, 33100, Italy |
| Email: | eros.digiorgio@uniud.it |
| Phone: | +39/0432494338 |
| Funding Source: | PRIN PNRR |
Subject:
| Subject ID: | SU003332 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Species Group: | Mammals |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Factor |
|---|---|---|
| SA351711 | AGA1 | AGA |
| SA351712 | AGA3 | AGA |
| SA351713 | AGA2 | AGA |
| SA351714 | SGA3 | SGA |
| SA351715 | SGA1 | SGA |
| SA351716 | SGA2 | SGA |
| Showing results 1 to 6 of 6 |
Collection:
| Collection ID: | CO003325 |
| Collection Summary: | The study involved women recruited from the Clinic of Obstetrics and Gynaecology at the University Hospital of Udine between May 2021 and August 2022. Fetal growth was monitored through sequential ultrasound examinations, including first-trimester screenings for chromosomal abnormalities and major defects, followed by second-trimester screenings for anatomical abnormalities, and two growth assessments at 29 weeks of gestation, with a minimum two-week interval between them. Post-delivery, placentas underwent both macroscopic and microscopic examinations to ensure suitability for the study. Inclusion criteria required participants to be at least 18 years old, have a singleton pregnancy with a live fetus at the time of ultrasound and delivery, while exclusion criteria comprised prenatally detected fetal anomalies, maternal endocrine disorders (e.g., pre-existing diabetes, hypothyroidism, hyperthyroidism), maternal hypertension, pregnancy-related diseases not attributed to isolated fetal growth disorders (e.g., gestational diabetes, cholestasis), multiple pregnancies, and severe maternal psychiatric disorders. Recruitment and data collection began following informed consent from the participants. Placentas from newborns with appropriate weight for gestational age were defined AGA; placentas from newborns with a birth weight below the 3rd percentile for gestational age were defined SGA. Biopsy samples approximately 1 cm3 in size were obtained from the maternal side of the placenta. Villous tissue was isolated, subjected to thorough washing of maternal blood with saline solution and promptly frozen at -80 °C until further use. Samples stored at -80 °C were thawed on ice and homogenized in a ball-mill grinder at 30 Hz for 20s. 400 μL solution (Methanol : Water = 7:3, V/V) containing internal standard was mixed with 20 mg of ground sample and mixed in a shaker at 2500 rpm for 5 min. The mixture was placed on ice for 15 min and centrifuged at 12000 rpm for 10 min (4 °C). |
| Sample Type: | Placenta |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR003341 |
| Treatment Summary: | No treatment |
Sample Preparation:
| Sampleprep ID: | SP003339 |
| Sampleprep Summary: | 300 μL of the supernatant was collected and placed in -20 °C for 30 min. The sample was then centrifuged at 12000 rpm for 3 min (4 °C). A 200 μL aliquot of the supernatant was subjected to LC/MS analysis by using Ultra Performance Liquid Chromatography (UPLC) (ExionLC 2.0, https://sciex.com/) and Quadrupole-Time of Flight Spectrometry (TripleTOF 6600+, AB SCIEX). |
Combined analysis:
| Analysis ID | AN005269 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | ExionLC 2.0 |
| Column | Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) |
| MS Type | ESI |
| MS instrument type | Triple quadrupole |
| MS instrument name | ABI Sciex 6500 QTrap |
| Ion Mode | UNSPECIFIED |
| Units | Coefficient of variation (CV) value |
Chromatography:
| Chromatography ID: | CH003987 |
| Chromatography Summary: | LC/MS run was performed at Metware Biotechnology (Woburn, MA USA). Analyst 1.6.3 was used to process mass spectrum data. |
| Instrument Name: | ExionLC 2.0 |
| Column Name: | Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) |
| Column Temperature: | 40 |
| Flow Gradient: | A:B 95:5 V/V at 0 min, 10:90 V/V at 10.0 min, 10:90 V/V at 11.0 min, 95:5 V/V at 11.1 min, 95:5 V/V at 14.0 min |
| Flow Rate: | 0.4 ml/min |
| Solvent A: | 100% ultrapure water; 0.1% formic acid |
| Solvent B: | 100% acetonitrile; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS005000 |
| Analysis ID: | AN005269 |
| Instrument Name: | ABI Sciex 6500 QTrap |
| Instrument Type: | Triple quadrupole |
| MS Type: | ESI |
| MS Comments: | LIT and triple quadrupole (QQQ) scans were acquired on a triple quadrupole-linear ion trap mass spectrometer (QTRAP), QTRAP LC-MS/MS System, equipped with an ESI Turbo Ion-Spray interface, operating in positive and negative ion mode and controlled by Analyst 1.6.3 software (Sciex). The ESI source operation parameters were as follows: source temperature 500°C; ion spray voltage (IS) 5500 V (positive), -4500 V (negative); ion source gas I (GSI), gas II (GSII), curtain gas (CUR) were set at 50, 50, and 25.0 psi, respectively; the collision gas (CAD) was high. Instrument tuning and mass calibration were performed with 10 and 100 μmol/L polypropylene glycol solutions in QQQ and LIT modes, respectively. A specific set of MRM transitions were monitored for each period according to the metabolites eluted within this period.The mixed samples first underwent untargeted metabolomics detection. Metabolites were analyzed qualitatively with in-house database MWDB, integrated public database (including Metlin, HMDB, and KEGG), AI database, and MetDNA. The identified metabolites were integrated with the in-house database MWDB. Lastly, quantification using MRM mode was performed for all samples based on the newly integrated database. Metabolites were quantified by triple quadrupole mass spectrometry with multiple reaction monitoring (MRM). In MRM mode, the first quadrupole screens the precursor ions for the target compound and excludes ions of other molecular weights. After ionization induced by the impact chamber, the precursor ion is fragmented, and a characteristic fragment ion is selected through the third quadrupole and excludes the interference of other untargeted ions. By selecting a particular fragment ion, quantification is more accurate and reproducible.Based on the raw data file ALL_sample_data_raw.xlsx, the missing values were first filled in using 1/5 of the minimum value of each row (metabolite), and then the CV value of the QC sample was calculated, and the metabolites with a CV value less than 0.3 were retained to obtain the final data file |
| Ion Mode: | UNSPECIFIED |
