Introduction
Methods
Variable | Gene expression | DNA methylation | ||
---|---|---|---|---|
Normal pregnancy | GDM pregnancy | Normal pregnancy | GDM pregnancy | |
Maternal data | ||||
No. of individuals used for cell isolation | 8 | 14 | 9 | 9 |
No. of cell isolations (AEC/VEC) | 8/8 | 10/11 | 9/9 | 9/5 |
Age (years) | 34.0 ± 7.3 | 32.8 ± 7.9 | 28.4 ± 6.3 | 32.7 ± 6.6 |
Gestational age (weeks) | 39.6 ± 1.5 | 38.9 ± 1.2 | 40.8 ± 1.5 | 39.2 ± 1.3* |
Height (m) | 1.66 ± 0.09 | 1.66 ± 0.06 | 1.70 ± 0.04 | 1.70 ± 0.05 |
Weight before pregnancy (kg) | 77.3 ± 17.5 | 83.0 ± 16.6 | 75.0 ± 11.6 | 83.6 ± 18.5 |
BMI before pregnancy | 27.7 ± 3.8 | 30.1 ± 5.6 | 25.8 ± 3.1 | 28.6 ± 7.6 |
Weight before birth (kg) | 92.8 ± 20.0 | 95.1 ± 18.1 | 90.2 ± 11.5 | 94.6 ± 17.6 |
BMI before birth | 33.3 ± 4.3 | 34.8 ± 5.8 | 30.1 ± 4.9 | 33.0 ± 6.6 |
Gestational weight gain (kg) | 15.5 ± 4.2 | 12.1 ± 9.6 | 15.2 ± 2.7 | 10.9 ± 10.3 |
CRP (nmol/l) | 99 ± 87 | 56 ± 49* | 92 ± 88 | 54 ± 52 |
HbA1c (mmol/mol) | ND | 38.8 ± 2.2 | ND | 37.7 ± 2.3 |
HbA1c (%) | ND | 5.7 ± 0.2 | ND | 5.6 ± 0.2 |
OGTT glucose (mmol/l) | ||||
Fasting | 4.35 ± 0.44 | 5.11 ± 0.42* | 4.35 ± 0.23 | 5.56 ± 0.66* |
1 h | 6.33 ± 0.96 | 10.20 ± 1.91* | 6.23 ± 1.14 | 9.32 ± 2.33* |
2 h | 5.64 ± 0.63 | 7.05 ± 1.45* | 5.33 ± 0.73 | 6.35 ± 1.54* |
GDM classification (A1/A2) | 9/5 | 4/5 | ||
Neonatal data | ||||
Male/female ratio | 4/4 | 6/8 | 4/5 | 4/5 |
Offspring weight (g) | 3547 ± 428 | 3275 ± 409 | 3443 ± 482 | 3318 ± 365 |
Offspring length (cm) | 51.0 ± 2.1 | 50.4 ± 2.0 | 50.4 ± 2.7 | 50.6 ± 2.7 |
Placental weight (g) | 515 ± 190 | 620 ± 188 | 619 ± 195 | 595 ± 159 |
Fetal ponderal index | 26.7 ± 2.0 | 25.5 ± 2.2 | 26.8 ± 2.6 | 25.9 ± 4.6 |
Fetus/placenta weight ratio | 6.25 ± 1.37 | 5.72 ± 1.74 | 5.89 ± 1.44 | 6.02 ± 1.78 |
Cord blood insulin (pmol/l) | ND | 223 ± 269 | 150 ± 177 | 181 ± 285 |
Cord blood C-peptide (nmol/l) | ND | 1.06 ± 0.93 | ND | 0.60 ± 0.23 |
Cell culture data | ||||
Cell isolation passage | 6.1 ± 1.2 | 6.6 ± 1.1 | 5.4 ± 1.0 | 4.8 ± 0.6 |
Results
Molecular function | p value | Scorea |
---|---|---|
DNA methylation | ||
AEC | ||
Cellular function and maintenance | 6.94 × 10−6 to 3.87 × 10−2 | 176 |
Cellular assembly and organisationb | 2.86 × 10−5 to 3.87 × 10−2 | 114 |
Post-translational modification | 1.54 × 10−4 to 3.77 × 10−2 | 26 |
Cell morphologyb | 2.39 × 10−4 to 4.01 × 10−2 | 92 |
Cellular development | 2.39 × 10−4 to 4.40 × 10−2 | 147 |
VEC | ||
Cellular function and maintenance | 8.24 × 10−4 to 4.91 × 10−2 | 53 |
Molecular transport | 8.24 × 10−4 to 4.91 × 10−2 | 51 |
Cell morphologyb | 9.34 × 10−4 to 4.58 × 10−2 | 45 |
Cell-to-cell signalling and interaction | 9.34 × 10−4 to 4.94 × 10−2 | 48 |
Cellular compromise | 9.34 × 10−4 to 2.89 × 10−2 | 14 |
Gene expression | ||
AEC | ||
Cell cycle | 8.42 × 10−22 to 1.26 × 10−2 | 159 |
Cellular assembly and organisationb | 8.42 × 10−22 to 1.11 × 10−2 | 106 |
DNA replication, recombination and repair | 8.42 × 10−22 to 1.11 × 10−2 | 159 |
Cellular movementb | 2.54 × 10−8 to 1.11 × 10−2 | 89 |
Cellular growth and proliferation | 1.03 × 10−6 to 1.15 × 10−2 | 234 |
VEC | ||
Cell cycle | 1.75 × 10−6 to 1.83 × 10−2 | 48 |
Cell death and survival | 4.96 × 10−5 to 1.36 × 10−2 | 25 |
Cellular assembly and organisationb | 7.46 × 10−5 to 1.67 × 10−2 | 46 |
Cellular function and maintenance | 7.46 × 10−5 to 1.67 × 10−2 | 38 |
DNA replication, recombination and repair | 7.46 × 10−5 to 1.74 × 10−2 | 24 |
Gene symbol | Gene name | Direction of expression and methylation change |
---|---|---|
EGFR
| Epidermal growth factor receptor | Concordant in AEC and VEC Upregulated in AEC and downregulated in VEC |
GABBR1
| γ-Aminobutyric acid (GABA) B receptor, 1 | Concordant in AEC and VEC Upregulated in AEC and VEC |
LMF1
| Lipase maturation factor 1 | Concordant in VEC Upregulated in AEC and VEC |
NCKAP5
| NCK-associated protein 5 | Concordant in AEC and VEC Upregulated in AEC and VEC |
SKIL
| SKI-like oncogene | Concordant in VEC Upregulated in AEC and VEC |
SULF2
| Sulfatase 2 | Concordant in VEC Upregulated in AEC and VEC |
Regulation | Molecular function | p value | Scorea |
---|---|---|---|
AEC | |||
Hypomethylated/upregulated | Cell morphologyb | 5.79 × 10−7 to 1.63 × 10−2 | 40 |
Cellular movementb | 2.54 × 10−5 to 1.56 × 10−2 | 35 | |
Cell-to-cell signalling and interaction | 5.75 × 10−5 to 1.63 × 10−2 | 28 | |
Carbohydrate metabolism | 1.98 × 10−4 to 1.63 × 10−2 | 14 | |
Cellular development | 1.98 × 10−4 to 1.63 × 10−2 | 33 | |
Hypermethylated/downregulated | Cell-to-cell signalling and interaction | 2.18 × 10−5 to 4.61 × 10−2 | 11 |
Cellular compromise | 2.18 × 10−5 to 1.82 × 10−2 | 10 | |
Molecular transport | 5.86 × 10−4 to 4.74 × 10−2 | 10 | |
Cell cycle | 7.69 × 10−4 to 4.86 × 10−2 | 11 | |
Cellular assembly and organisationb | 7.69 × 10−4 to 4.61 × 10−2 | 16 | |
VEC | |||
Hypomethylated/upregulated | Carbohydrate metabolism | 4.55 × 10−5 to 1.17 × 10−2 | 4 |
Small molecule biochemistry | 4.55 × 10−5 to 2.72 × 10−2 | 11 | |
Cell morphologyb | 1.51 × 10−4 to 2.72 × 10−2 | 23 | |
Cellular function and maintenance | 1.51 × 10−4 to 2.62 × 10−2 | 20 | |
Cell-to-cell signalling and interaction | 1.58 × 10−4 to 2.72 × 10−2 | 11 | |
Hypermethylated/downregulated | Cell cycle | 1.48 × 10−4 to 4.85 × 10−2 | 4 |
Protein synthesis | 4.12 × 10−4 to 1.42 × 10−2 | 6 | |
Cellular movementb | 4.76 × 10−4 to 4.58 × 10−2 | 3 | |
Cell death and survival | 1.17 × 10−3 to 4.98 × 10−2 | 5 | |
Cell morphologyb | 1.42 × 10−3 to 4.71 × 10−2 | 4 |