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Endocrine Abstracts (2021) 77 OP3.2 | DOI: 10.1530/endoabs.77.OP3.2

SFEBES2021 Oral Poster Presentations Reproductive and Neuroendocrinology (4 abstracts)

An ex-vivo human placental model demonstrates that temporal fluctuations in maternal glucose in gestational diabetes alter placental transcriptome networks associated vascular development and angiogenesis

Abigail Byford , Katy Walsh , Eleanor Scott & Karen Forbes

University of Leeds, Leeds, United Kingdom

Aims: Women with gestational diabetes (GDM) who deliver large-for-gestational age (LGA) infants have subtle (1-1.5mM) differences in temporal maternal glucose control detectable by continuous glucose monitoring (CGM), compared to women who deliver appropriate-for-gestational-age (AGA) infants. It is unclear how these subtle changes cause LGA, but LGA has been linked to placental dysfunction. We aimed to develop an ex-vivo human placental model to mimic subtle differences in temporal maternal glucose in GDM and assess the impact on the placental transcriptome and function.

Methods: Human term villous explants (n = 7) from uncomplicated pregnancies were cultured for 48-h with medium changes every 6-18 h in variable (5/5.5mM) or constant (7 mM) glucose. Glucose concentrations assessed in medium at each timepoint were compared to CGM profiles from women with GDM/AGA/LGA. mRNA sequencing was performed on explants (n = 5). Functional enrichment was performed on differentially expressed genes (DEGs; P < 0.05, log2foldchange -0.5< or >0.5) by over representation analysis (ORA) and ingenuity pathway analysis (IPA).

Results: Input levels of 5-5.5 mm glucose represented CGM profiles from GDM women with stable/appropriate glucose control (normoglycaemia) delivering AGA infants, whereas 7 mM glucose reflected CGM profiles from GDM women with suboptimal glucose control (hyperglycaemia) delivering LGA infants.Hyperglycaemia altered the placental transcriptome (456 downregulated and 128 upregulated genes). ORA revealed that DEGs were associated with gene ontology terms and pathways including response to chemokines (P = 2.36E-06), regulation of vascular development (P = 4.97E-06), angiogenesis (P = 1.23E-04) and regulation of insulin-like growth factor (IGF) transport/uptake (P = 4.40E-05). IPA revealed several associated canonical pathways including atherosclerosis (P = 8.99E-06), type II diabetes signalling (P = 1.21E-02) and pathways associated with IL-17a signalling.

Conclusions: The altered placental transcriptome observed using this physiologically relevant model suggests that subtle changes in maternal glucose may lead to LGA by influencing key developmental and inflammatory pathways in the placenta.

Volume 77

Society for Endocrinology BES 2021

Edinburgh, United Kingdom
08 Nov 2021 - 10 Nov 2021

Society for Endocrinology 

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