 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 01, 2024 |
| Title |
Obesogenic diet in mice leads to inflammation and oxidative stress in the mother in association with sex-specific changes in fetal development, inflammatory markers and placental transcriptome |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Obesity during pregnancy is related to adverse maternal and neonatal outcomes. Factors involved in these outcomes may include increased maternal insulin resistance, inflammation, oxidative stress and nutrient mishandling. The placenta is the primary determinant of fetal outcomes, and its function can be impacted by maternal obesity. The aim of this study in mice was to determine the effect of obesity on maternal lipid handling, inflammatory and redox state, and placental oxidative stress, inflammatory signalling, and gene expression relative to female and male fetal growth. Here we showed that HFHS diet induced, in the dams, hepatic steatosis, oxidative stress (reduced catalase, elevated protein oxidation) and activation of pro-inflammatory pathways (p38-MAPK) along with imbalanced circulating cytokine concentrations (increased IL-6 and decreased IL-5 and IL-17A). HFHS fetuses were asymmetrically growth-restricted, showing sex-specific changes in circulating cytokines (GM-CSF, TNF-a, IL-6 and IFN-g). Morphology of the placenta Lz was modified by a HFHS diet, in association with sex-specific alterations in the expression of genes and proteins implicated in oxidative stress, inflammation, and stress signalling. Placental gene expression changes were comparable to that seen in models of intrauterine inflammation and were related to a transcriptional network involving transcription factors, LYL1 and PLAG1. In summary, this study shows that fetal growth restriction with maternal obesity is related to elevated oxidative stress, inflammatory pathways, and sex-specific placental changes. Our data are important given the marked consequences and the rising rates of obesity worldwide.
|
| |
|
| Overall design |
Female mice were fed control or obesogenic high-fat/high-sugar diet (HFHS) from 9 weeks prior to and during pregnancy. On day 18.5 of pregnancy, maternal plasma, and liver, placenta, and fetal serum were collected to examine the immune and redox state. The placental labyrinth zone (Lz) was dissected for RNA-sequencing analysis of gene expression changes.
|
| |
|
| Contributor(s) |
Candia AA, Lean SC, Zhang CX, McKeating DR, Cochrane A, Gulacsi E, Herrera EA, Krause BJ, Sferruzzi-Perri AN |
| Citation(s) |
38671859 |
| Submission date |
Mar 20, 2024 |
| Last update date |
May 01, 2024 |
| Contact name |
Brian Yee Hong Lam |
| E-mail(s) |
yhbl2@cam.ac.uk
|
| Organization name |
University of Cambridge
|
| Department |
Metabolic Research Laboratories
|
| Street address |
Box 289 Addenbookes Hospital, Hills Road
|
| City |
Cambridge |
| ZIP/Postal code |
CB2 0QQ |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (24)
|
| GSM8155969 |
Placental labyrinth zone Ctrl_F_4075_01 |
| GSM8155970 |
Placental labyrinth zone Ctrl_F_4085_02 |
| GSM8155971 |
Placental labyrinth zone Ctrl_F_4091_03 |
| GSM8155972 |
Placental labyrinth zone Ctrl_F_4061_04 |
| GSM8155973 |
Placental labyrinth zone Ctrl_F_4126_05 |
| GSM8155974 |
Placental labyrinth zone Ctrl_F_4154_06 |
| GSM8155975 |
Placental labyrinth zone Ctrl_M_4075_07 |
| GSM8155976 |
Placental labyrinth zone Ctrl_M_4085_08 |
| GSM8155977 |
Placental labyrinth zone Ctrl_M_4091_09 |
| GSM8155978 |
Placental labyrinth zone Ctrl_M_4061_10 |
| GSM8155979 |
Placental labyrinth zone Ctrl_M_4154_11 |
| GSM8155980 |
Placental labyrinth zone HFHS_F_3996_01 |
| GSM8155981 |
Placental labyrinth zone HFHS_F_4062_02 |
| GSM8155982 |
Placental labyrinth zone HFHS_F_4068_03 |
| GSM8155983 |
Placental labyrinth zone HFHS_F_4073_04 |
| GSM8155984 |
Placental labyrinth zone HFHS_F_4140_05 |
| GSM8155985 |
Placental labyrinth zone HFHS_F_4177_06 |
| GSM8155986 |
Placental labyrinth zone HFHS_M_3996_07 |
| GSM8155987 |
Placental labyrinth zone HFHS_M_4062_08 |
| GSM8155988 |
Placental labyrinth zone HFHS_M_4068_09 |
| GSM8155989 |
Placental labyrinth zone HFHS_M_4073_10 |
| GSM8155990 |
Placental labyrinth zone HFHS_M_4140_11 |
| GSM8155991 |
Placental labyrinth zone HFHS_M_4177_12 |
| GSM8155992 |
Placental labyrinth zone Ctrl_M_4126_12 |
|
| Relations |
| BioProject |
PRJNA1090037 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE262011_raw_counts.tsv.gz |
963.4 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...