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Series GSE112755 Query DataSets for GSE112755
Status Public on Feb 13, 2019
Title The placental transcriptome in late gestational hypoxia resulting in murine intrauterine growth restriction predicts adult cardiometabolic disease
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often results in short- and long- term sequelae for offspring, including risk for adult cardiovascular disease (CVD). The mechanisms underlying IUGR are poorly understood, though poor blood flow and oxygen/nutrient provision to the IUGR fetus are thought to be the common endpoints of disease. Though several animal models of IUGR exist, few demonstrate later phenotypes of CVD despite a large body of evidence in humans linking IUGR and adult CVD onset. We thus hypothesized that in murine pregnancy, maternal late gestational hypoxia (LG-H) exposure resulting in IUGR would result in (1) adult phenotypes of CVD in hypoxia-exposed offspring, and (2) the placental transcriptome will demonstrate alterations that can be linked to risk of later disease. After subjecting pregnant mice to hypoxia (10.5% oxygen) from gestational day (GD) 14.5 to 18.5, we collected placentas at GD19. We examined RNA isolated from these placentas to perform RNA sequencing and analysis. Functional gene and cluster-based analysis suggest multiple changes in structural and functional genes important for placental health, with the top dysregulation involving vascular and metabolic pathways. Concordantly, a ~ 10% decrease in birthweights and ~30% decrease in litter size after LG-H (p<0.05) was observed, suggesting an environment of placental insufficiency. We also found that offspring exposed in-utero to LG-H exhibit CVD at 4 months of age, with males being worse than females, supporting developmental programming. Specifically, males exhibit increased body weight and an enlarged heart size, whereas both males and females develop hypertension, elevated abdominal fat, elevated leptin and elevated total cholesterol levels with aging. In summary, LG-H exposure in the pregnant mouse mimics human placental insufficiency related IUGR. The placentas of these exposed fetuses demonstrate a transcriptional response to the stressor of gestational hypoxia and predicts cardiovascular and metabolic effects that culminate into hypertension and adiposity with dyslipidemia.
Overall design Pregnant female mice were randomly assigned to two groups: 1) late gestation-room air (LG-RA) pregnant mice which were house in standard conditions, and 2) late gestation-hypoxia (LG-H) pregnant mice were exposed to hypoxia for 4 days (days 14.5 to 18.5 of gestation).
Contributor(s) Chu A, Casero D, Thamotharan S, Cosi A, Wadehra M, Devaskar SU
Citation(s) 30718791
Submission date Apr 05, 2018
Last update date Feb 13, 2019
Contact name David Casero
Phone 3108250274
Organization name UCLA
Department Pathology and Laboratory Medicine
Street address 610 Charles Young Drive East
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (15)
GSM3082906 Placenta 1, control
GSM3082907 Placenta 2, control
GSM3082908 Placenta 3, control
BioProject PRJNA448908
SRA SRP137723

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Supplementary file Size Download File type/resource
GSE112755_PlacentalHypoxia.genesfpkm.txt.gz 636.4 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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