Gestational diabetes alters microRNA signatures in human feto-placental endothelial cells depending on fetal sex.
Jasmin StrutzSilvija CviticHubert HacklKarl KashoferHannah M AppelAndrea ThüringerGernot DesoyePieter KoolwijkUrsula HidenPublished in: Clinical science (London, England : 1979) (2018)
MicroRNAs (miRNAs), small non-coding RNAs, have emerged as important, epigenetic regulators of endothelial function. Metabolic disturbances such as diabetes alter miRNA expression. In adults, the miRNA transcriptome as well as endothelial function differ between the sexes. Here, we hypothesized that metabolic disturbances associated with gestational diabetes (GDM) alter miRNA signatures in feto-placental endothelial cells (fpEC), dependent on fetal sex. We isolated human primary fpEC after normal and GDM-complicated pregnancies with male and female neonates and screened for differential miRNA expression using next-generation miRNA sequencing. To test for miRNAs commonly regulated in fpEC of female and male progeny, data were stratified for fetal sex and maternal body mass index (BMI). Analyses were also performed separately for female and male fpEC, again accounting for maternal BMI as covariate. Potential biological pathways regulated by the altered set of miRNAs were determined using mirPath software. Maternal GDM altered 26 miRNA signatures when male and female fpEC were analyzed together. Separate analysis of male versus female fpEC revealed 22 GDM affected miRNAs in the females and only 4 in the males, without overlap. Biological functions potentially modulated by the affected miRNAs related to 'Protein Processing in Endoplasmic Reticulum' and 'Proteoglycans in Cancer'. Maternal GDM alters miRNA signatures in fpEC, and biological functions affected by these miRNAs relate to well-known adverse functional consequences of diabetes on endothelium. GDM effects were highly dependent on fetal sex with miRNA signatures in female fpEC being more susceptible to metabolic derangements of GDM than miRNAs in male fpEC.
Keyphrases
- endothelial cells
- body mass index
- pregnancy outcomes
- genome wide
- type diabetes
- birth weight
- single cell
- poor prognosis
- gene expression
- weight gain
- pregnant women
- nitric oxide
- squamous cell carcinoma
- binding protein
- emergency department
- transcription factor
- high glucose
- risk assessment
- metabolic syndrome
- weight loss
- young adults
- human health
- amino acid
- induced pluripotent stem cells
- deep learning
- artificial intelligence
- climate change
- long non coding rna