Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2022) 86 P199 | DOI: 10.1530/endoabs.86.P199

SFEBES2022 Poster Presentations Metabolism, Obesity and Diabetes (96 abstracts)

Temporal periods of mild hyperglycaemia in pregnancies complicated by gestational diabetes and LGA alter placental transcriptomic networks associated with vascularisation and M2 hofbauer cell polarisation

Abigail Byford 1 , Katy Walsh 1 , Beth Holder 2 , Eleanor Scott 1 & Karen Forbes 1

1University of Leeds, Leeds, United Kingdom; 2Imperial College London, London, United Kingdom

Background: Gestational diabetes (GDM) leads to an increased risk of delivering large-for-gestational-age infants (LGA), which has been linked to altered placental vascular development. Women with GDM who deliver LGA infants have temporal periods of mild hyperglycaemia, detectable by continuous glucose monitoring (CGM), compared to women who deliver appropriate-for-gestational-age infants (AGA). This study aimed to assess the impact of physiological periods and levels of hyperglycaemia on placental gene expression and function.

Methods: To mimic in-vivo glucose levels in GDM-AGA and GDM-LGA pregnancies, healthy term placental explants were cultured for 48-hours in fluctuating 5/5.5 mM (normoglycaemia) or constant 7 mM (mild hyperglycaemia) glucose, respectively. RNAseq (n=5) and functional enrichment (over representation, Ingenuity pathway (IPA) and Cytoscape analyses) were performed. TMT-proteomics was conducted on placental macrophages (Hofbauer cells; HBCs) isolated from healthy term placentae (n=6). Immunohistochemistry of CD206 and CD163 was performed assess localisation of M2 HBCs (n=4).

Results: Mild hyperglycaemia altered 584 genes (P<0.05, log2foldchange >0.5 <-0.5). Differentially expressed genes (DEGs) were enriched in immune/inflammatory and vascular development pathways (P<0.001). In IPA, several biological functions were predicted to be decreased by mild hyperglycaemia, including angiogenesis (P=1.44E-10, Z-score=-3.386), vasculogenesis (P=5.88E-10, Z-Score=-3.465), and activation of macrophages (P=1.94E-07, Z-score= -2.017). A comparison of DEGs to the HBC proteome revealed that 87 DEGs are produced by HBCs, including regulators of placental vascularisation (e.g., PECAM1, IL1B, PTGS2). DEGs were associated with an M2 phenotype when compared to M1/M2 macrophage transcriptomics (GSE5099). In immunohistochemistry, M2 markers, CD206 and CD163, were localised to the villous stroma, and in close proximity to fetal blood vessels.

Conclusions: Mild hyperglycaemia altered the placental transcriptome. Given that M2 HBCs are known to play roles in placental vascularisation, mild hyperglycaemia may activate M2 HBCs which in turn contribute to altered placental angiogenesis and may ultimately lead to LGA.

Volume 86

Society for Endocrinology BES 2022

Harrogate, United Kingdom
14 Nov 2022 - 16 Nov 2022

Society for Endocrinology 

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